OBJECTIVE

To synthesize the cost-effectiveness (CE) of interventions to prevent and control diabetes, its complications, and comorbidities.

RESEARCH DESIGN AND METHODS

We conducted a systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association (ADA) and published between January 1985 and May 2008. We categorized the strength of evidence about the CE of an intervention as strong, supportive, or uncertain. CEs were classified as cost saving (more health benefit at a lower cost), very cost-effective (≤$25,000 per life year gained [LYG] or quality-adjusted life year [QALY]), cost-effective ($25,001 to $50,000 per LYG or QALY), marginally cost-effective ($50,001 to $100,000 per LYG or QALY), or not cost-effective (>$100,000 per LYG or QALY). The CE classification of an intervention was reported separately by country setting (U.S. or other developed countries) if CE varied by where the intervention was implemented. Costs were measured in 2007 U.S. dollars.

RESULTS

Fifty-six studies from 20 countries met the inclusion criteria. A large majority of the ADA recommended interventions are cost-effective. We found strong evidence to classify the following interventions as cost saving or very cost-effective: (I) Cost saving— 1) ACE inhibitor (ACEI) therapy for intensive hypertension control compared with standard hypertension control; 2) ACEI or angiotensin receptor blocker (ARB) therapy to prevent end-stage renal disease (ESRD) compared with no ACEI or ARB treatment; 3) early irbesartan therapy (at the microalbuminuria stage) to prevent ESRD compared with later treatment (at the macroalbuminuria stage); 4) comprehensive foot care to prevent ulcers compared with usual care; 5) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes. (II) Very cost-effective— 1) intensive lifestyle interventions to prevent type 2 diabetes among persons with impaired glucose tolerance compared with standard lifestyle recommendations; 2) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3) intensive glycemic control as implemented in the UK Prospective Diabetes Study in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 4) statin therapy for secondary prevention of cardiovascular disease compared with no statin therapy; 5) counseling and treatment for smoking cessation compared with no counseling and treatment; 6) annual screening for diabetic retinopathy and ensuing treatment in persons with type 1 diabetes compared with no screening; 7) annual screening for diabetic retinopathy and ensuing treatment in persons with type 2 diabetes compared with no screening; and 8) immediate vitrectomy to treat diabetic retinopathy compared with deferred vitrectomy.

CONCLUSIONS

Many interventions intended to prevent/control diabetes are cost saving or very cost-effective and supported by strong evidence. Policy makers should consider giving these interventions a higher priority.

The cost of diabetes in the U.S. in 2007 was $174 billion (1). Many interventions can reduce the burden of this disease. However, health care resources are limited; thus, interventions for diabetes prevention/control should be prioritized. We wanted to compare the effectiveness and costs of various interventions to find those that were the most effective for the least expense. Cost-effective analysis is a useful tool for this purpose. Such analyses consist of compiling incremental cost-effectiveness ratios (ICERs), which are calculated as a ratio of the difference in costs to the difference in effectiveness between the intervention being evaluated and the comparison intervention.

With the same health outcome indicator, ICERs of interventions are comparable. Therefore, these ICERs can make it easier to decide how to allocate resources. Although many cost-effectiveness (CE) analyses of diabetes interventions have been published, their qualities and conclusions vary. A systematic review, which appraises individual studies and summarizes results, would aid policy makers and clinicians in prioritizing interventions to prevent or treat diabetes and its complications.

Few investigators have conducted systematic reviews of the CE of diabetes interventions (2,,5). The systematic review presented here, following the Cochrane Collaboration's protocol (6), includes all English language studies available from 1985 to May 2008. The interventions included only those recommended by the 2008 American Diabetes Association (ADA) Standards of Medical Care in Diabetes (7).

Study selection and protocols for review

We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Sociological Abstracts (Soc Abs), Web of Science (WOS), and Cochrane databases to identify relevant studies. We created a search strategy involving medical subject headings. The key words—and what each indicated—were:

  • Indicating diabetes: 26 key words indicating the disease of diabetes, such as “type 1 diabetes,” “type 2 diabetes,” “impaired glucose tolerance,” and “insulin resistance”;

  • Indicating costs: (“cost or expenditure”) OR (“costs and cost analysis”) OR (“health care costs”) OR (“cost of illness”);

  • Indicating effectiveness: (“benefit”) OR (“life years”) OR (“quality-adjusted life years”) OR (“disability adjusted life years”);

  • Indicating CE analysis: [(key words for costs) AND (keywords for effectiveness)] OR (“cost-benefit analysis”) OR (“cost-effectiveness analysis”) OR (“cost-utility analysis”) OR (“economic evaluation”).

Database searches were based on matches in all four keyword categories. Reference lists of all the included articles were screened for additional citations, and Diabetes Care was reviewed manually, issue by issue, as the journal was expected to be highly relevant.

Criteria for inclusion in the review were 1) original CE analysis; 2) intervention directed toward patients with type 1, type 2, or gestational diabetes mellitus (GDM) and recommended in the 2008 ADA standards for medical care (7); 3) outcomes were measured as life years gained (LYGs) or quality-adjusted life years gained (QALYs); and 4) publication in the English language occurred between January 1985 and May 2008 (2). To ensure that only studies with acceptable quality were included, we limited the analysis to studies considered good or excellent according to a 13-item quality-assessment tool based on the British Medical Journal authors' guide for economic studies (8).

To make ICERs comparable across the studies, all costs are expressed as 2007 U.S. dollars with adjustment from other currencies, as needed, using the Federal Reserve Bank's annual foreign exchange rates (9) and from other cost years using the Consumer Price Index (10). If a study did not mention the year used in cost calculations, we assumed cost was as of one year before publication. ICERs were expressed as dollars per QALY or dollars per LYG and were rounded to the nearest hundred dollars per QALY or LYG.

Classification of cost-effectiveness of interventions

Interventions were classified based on the level of CE by convention as described in the literature (2,11,12)—cost saving (an intervention generates a better health outcome and costs less than the comparison intervention) or cost neutral (ICER = 0); very cost-effective (0 < ICER ≤ $25,000 per QALY or LYG); cost-effective ($25,000 < ICER ≤ $50,000 per QALY or LYG); marginally cost-effective ($50,000 < ICER ≤ $100,000 per QALY or LYG); or not cost-effective (>$100,000 per QALY or LYG)—and whether evidence for the intervention's CE was strong, supportive, or uncertain as described below.

There were two grades of evidence included in the “strong” group. Grade 1 was defined as 1) CE of the intervention was evaluated by two or more studies; 2) study quality was rated good or excellent; 3) effectiveness of interventions based on well-conducted, randomized clinical trials with adequate power and generalizable results or meta-analysis or a validated simulation model; 4) effectiveness of interventions rated as level A (clear evidence from well-conducted, generalizable, randomized controlled trials that were adequately powered; compelling nonexperimental evidence, i.e., the all or none rule developed by the Centre for Evidence-Based Medicine at the University of Oxford, U.K.) or level B (supportive evidence from well-conducted cohort studies or supportive evidence from a well-conducted case-control study) according to the 2008 ADA standards of medical care (7); and 5) similar ICERs reported across the studies. Grade 2 was defined as the same as Grade 1 except that the CE was based on only one study and the study was rated as excellent.

We called the level of evidence “supportive” if only one study, rated lower than excellent, evaluated the CE of the intervention or if the effectiveness of the intervention was supported by either level C evidence (supportive evidence from poorly controlled or uncontrolled studies, or conflicting evidence with the weight of evidence supporting the recommendation) or expert consensus (level E) in ADA recommendations (7). The term “uncertain” was used to describe interventions with inconsistent evidence about CE across studies.

Reporting the results of the systematic review

We reported the study results in two ways: 1) summarizing the key features and results for each included study; and 2) synthesizing the CE of the interventions based on the classification criteria described above. For the summary, we grouped interventions based on their intended purposes: a) preventing type 2 diabetes among high-risk persons; b) screening for undiagnosed type 2 diabetes and GDM; c) management of diabetes and risk factors for complications; d) screening for and early treatment of complications; and e) treatment of complications and comorbidities. We considered cases where the same intervention was applied to different populations or was compared with different interventions as different specific interventions and reported the ICERs separately. This was because both incremental costs and effectiveness of an intervention, and thus the ICERs, varied if the population and/or comparison group differed. If the CE of an intervention was evaluated from different study perspectives, we report the ICERs separately. We presented the ICERs in subgroups if their ICERs differed substantially from base-case analysis, and original studies reported the ICERs this way. If the study reported the ICERs only for population subgroups, we provided a range and, when available, trend of the ICERs. Finally, if a study used both LYGs and QALYs as study outcome measures, we reported the ICER in both costs per LYG and QALY.

In reporting the synthesized results, we applied the following rules: 1) We used the median ICER to represent the CE of an intervention if the intervention was evaluated by more than one study. 2) We reported the ICERs from the longer analytical time horizon if the intervention was evaluated from both short- and long-term perspectives. This was appropriate since many of the benefits of most diabetes prevention and control interventions would come from preventing diabetic complications, which occur later in life. 3) We chose the health care system as our primary study perspective for the purpose of cross-study and cross-intervention comparisons. This study perspective included all the medical costs incurred no matter who paid. 4) If the ICERs of an intervention differed substantially between the U.S. and other developed countries (mainly European countries, Australia, and Canada), we reported the summary results separately by labeling the ICER for the U.S. or for the other countries. 5) If the trial on which the CE of an intervention was based was conducted in a mixed population with type 1 or type 2 diabetes, we assumed the CE was the same for both types of diabetes.

The search yielded 9,461 abstracts. After reviewing the abstracts and subsequent reference tracking, we narrowed the focus to 197 possible original CE studies. Further review of the full text resulted in 56 CE studies that met our inclusion criteria. Figure 1 depicts the data abstraction process.

Figure 1

Selection of cost-effectiveness studies for systematic review of interventions to prevent and control diabetes.

Figure 1

Selection of cost-effectiveness studies for systematic review of interventions to prevent and control diabetes.

Close modal

Table 1 shows the detailed description of the CE studies that we included according to intervention type (13,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,70). We first grouped similar interventions together, then arranged them chronologically and by the first author's last name. Some studies that evaluated multiple interventions appear in more than one category. The information used to describe each study included the intervention being evaluated; comparison intervention, population, and country setting; data sources for the effectiveness of the intervention; study methods; quality of the study; analytical time horizon; discount rate (a rate that is used to convert future costs and benefits into their present values); and ICER.

Table 1

Description of the cost-effectiveness studies for diabetes interventions*

Source/study quality/countryStudy populationInterventionComparisonEffectiveness dataMethodology/analytical horizon/discount rateCost-effectiveness ratios (2007 U.S. $)
Preventing type 2 diabetes among high-risk individuals 
    Segal et al. 1998 (59)§ Australia Seriously obese or seriously obese with IGT Intensive diet and education Standard care Literature review 25 years 5% Cost saving 
 Overweight or obese IGT or NGT and IGT Group education in workplace on diet and physical activity for men Standard care   Cost saving 
 High-risk adults IGT or NGT and IGT General practitioner advice on healthy lifestyle Standard care   $1,000–$2,500/LYG 
 Overweight adults in general population Community-supported media campaign on obesity/sedentary lifestyle No campaign   Cost saving 
 Women with GDM history + NGT or IGT Intensive diet and behavioral modification Standard care   $1,300–$2,500/LYG 
    DPP 2003 (66) U.S. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) 3 years 0% $32,900/QALY; if in 10-person group, $11,100/QALY 
 IGT Metformin Standard advice on lifestyle   $134,000/QALY; if metformin cost reduced 50%, $76,500/QALY 
 IGT Intensive lifestyle modification‡‡ Standard advice on lifestyle   $69,400/QALY; if in 10-person group, $36,000/QALY 
 IGT Metformin‡‡ Standard advice on lifestyle   $133,400/QALY 
    Caro et al. 2004 (15) Canada IGT Intensive lifestyle modification No intervention DPP (n = 3,234), FDPS (n = 52) 10 years 5% $700/LYG 
IGT Metformin No intervention  Cost saving in LYG and QALY 
    Palmer et al. 2004 (50) Australia, France, Germany, Switzerland, U.K. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) Lifetime 5% except U.K.: cost 5%, effectiveness, 1.5% Cost saving except U.K.; U.K.: $8,300/LYG 
 IGT Metformin Standard advice on lifestyle   Cost saving, except UK; UK: $6,500/LYG 
    Eddy et al. 2005 (25) U.S. IGT Intensive lifestyle modification‡‡ No intervention DPP Multicenter RCT (n = 3,234) 30 years 3% $84,700/QALY; in 10-person group, $16,000/QALY 
 IGT Intensive lifestyle modification# No intervention   $192,600/QALY; in 10-person group, $36,400/QALY 
 IGT Metformin‡‡ No intervention   $47,900/QALY 
    Herman et al. 2005 (34) U.S. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) Lifetime 3% $1,500/QALY; in 10-person group, cost saving 
 Intensive lifestyle modification‡‡ Standard advice on lifestyle  $11,800/QALY 
  Metformin Standard advice on lifestyle   $42,000/QALY 
  Generic Standard advice on lifestyle   $2,400/QALY 
  Metformin‡‡    $40,200/QALY 
    Lindgren et al. 2007 (41) Sweden IGT Age 60 years BMI >25 kg/m2, FPG >6.1 mmol/l Intensive lifestyle intervention (6 years)‡‡ General lifestyle advice FDPS (n = 52) Lifetime 3% Cost saving not considering cost of extended life; $2,600/QALY including cost of extended life 
    Hoeger et al. 2007 (36) U.S. U.S. population age 45–74 years, overweight and obese (BMI ≥ 25 kg/m2) Groups Screening for IGT and IFPG, DPP lifestyle intervention with IGT + IFPG No screening and no lifestyle intervention DPP (n = 3,234) Lifetime 3% $10,600/QALY; in group settings, cost saving 
 Screening for IGT and IFPG, DPP lifestyle intervention with IFPG or IGT + IFPG No screening and lifestyle intervention   $12,300/QALY; in group settings, $344/QALY 
  Screening for IGT and IFPG, DPP lifestyle intervention with IGT + IFPG Screening for IGT and IFPG, following DPP lifestyle intervention with IFPG, IGT, or IFPG + IGT   $13,100/QALY 
  Screening and metformin treatment with IGT + IFPG No screening and treatment   $26,600/QALY 
  Screening and metformin treatment with IGT, IFPG, or IGT + IFPG No screening and treatment   $26,000/QALY 
Screening for undiagnosed type 2 diabetes and gestational diabetes 
    Centers for Disease Control and Prevention 1998 (16) U.S U.S. population 25 years and older One-time Opportunistic screening for undiagnosed type 2 diabetes starting at age 25 years, then treatment (universal screening) No screening and treatment until clinical diagnosis of type 2 diabetes  Lifetime 3% $374,900/LYG or $89,800/QALY; increasing with age (age ≥ 25 years) treatment (universal screening) 
     .      $57,100/LYG or $21,400/QALY (age 25–34 years) 
      $103,200/LYG or $29,700/QALY (age 35–44 years) 
      293,900/LYG or $70,100/QALY (age 45–54 years) 
      $1 million/LYG or $185,000/QALY (age 55–64 years) 
      $928,000/QALY (age ≥65) 
 African Americans:      
     age 25–34 years     $3,500/LYG or $1,300/QALY 
     age 35–44 years     $10,200/LYG or $3,100/QALY 
     age 45–54 years     $95,400/LYG or $19,600/QALY 
     age 55–64 years     $764,100/LYG or $112,600/QALY 
     age ≥65 years     $2 million/LYG or $500,000/QALY 
    Hoerger et al. 2004 (35) U.S. Persons with hypertension Targeted screening for undiagnosed diabetes among persons with hypertension No screening or treatment until clinical diagnosis of type 2 diabetes  Lifetime 3% $46,800–$130,500/QALY decreasing with age $70,500/QALY for age 45 years 
 U.S. population One-time opportunistic screening, then treatment (universal screening) No screening or treatment until clinical diagnosis of type 2 diabetes   $72,200–$189,100/QALY decreasing with age $183,500/QALY for age 45 years 
 U.S. population One-time opportunistic screening, then treatment (universal screening) Targeted screening, then treatment   $215,600–$699,800/QALY increasing with age 
    Nicolson et al. 2005 (44) U.S. 30-year-old pregnant women between 24–28 weeks' gestation Sequential method (50-g GCT + 100-g GTT)‡‡ No screening 75-g GTT A few unidentified RCTs <1 year** 0% Cost saving 
  100-g GTT‡‡ No screening or 75-g GTT method   Cost saving 
  100-g GTT‡‡ Sequential method   $35,200/QALY for maternal outcomes, $9,000/QALY for neonatal outcomes 
Intensive glycemic control 
    DCCT 1996 (65) U.S. Type 1 diabetes Intensive glycemic control through insulin management, self-monitoring, and outpatient visits. The goal was to achieve A1C level as normal as possible (6%) Conventional therapy (less intensive) DCCT Multicenter RCT (n = 1,441) Lifetime 3% $47,600/life year gained, $50,800/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes Intensive insulin therapy Conventional insulin therapy Literature review Lifetime 3%, 5%, 6% Reported results at 3% in the table $46,600/LYG 
    Scuffham et al. 2003 (58) U.K. Type 1 diabetes Continous subcutaneous insulin intervention for persons using insulin pump Multiple daily insulin injections 1 systematic review 1 meta-analysis 8 years 6% $10,200/QALY 
    Roze et al. 2005 (56) U.K. Type 1diabetes Continuous subcutaneous insulin infusion Multiple daily insulin injections DCCT (n = 1,441) mainly meta-analysis 60 years 3% $18,500/QALY 
    Eastman et al. 1997 (24) U.S. Newly diagnosed type 2 diabetes Intensive treatment targeting maintenance of A1C level at 7.2% Standard antidiabetic treatment targeting A1C level at 10% DCCT (n = 1,441) Lifetime 3% $17,400/QALY; sensitive to age at diabetes onset; CER <33,000 for age <50 years; $371,700/QALY for age 70–80 years 
    Gray et al. 2000 (30) U.K. Type 2 diabetes Intensive management with insulin or sulfonylurea aiming at FPG <6 mmol/l Conventional management (mainly through diet) aiming at FPG <15 mmol/l UKPDS Multicenter RCT (n = 5,120) 10 years** 6% Cost saving in trial; $1,100/event-free year gained in clinic setting 
    Wake et al. 2000 (70) Japan Type 2 diabetes Intensive insulin therapy through multiple insulin injections A1C <7% Conventional insulin injection therapy Kumamoto study RCT (n = 110) 10 years** 3% Cost saving 
    Clarke et al. 2001 (18) U.K. Newly diagnosed type 2 diabetes Overweight Intensive blood glucose control with metformin aiming at FPG <6 mmol/l Conventional treatment primarily with diet UKPDS (n = 5,120) Median 10.7 years** 6% Cost saving 
    Centers for Disease Control and Prevention 2002 (17) U.S. Newly diagnosed type 2 diabetes Intensive glycemic control with insulin or sulfonylurea aiming at FPG of 6 mmol/l Conventional glucose control (mainly diet) UKPDS (n = 5,120) Lifetime 3% $62,000/QALY; increasing rapidly with age at diagnosis: $14,400/QALY for age 25–34 years; $27,500–$56,000/QALY for age 35–54 years; > $100,000–$3.1 million for age 55–94 years 
      Cost saving under UKPDS cost scenario (no case management cost, much less self-testing, slightly fewer physician visits) but using U.S. unit cost 
    Clarke et al. 2005 (19) U.K. Newly diagnosed type 2 diabetes requiring insulin Intensive glycemic control with insulin or sulfonylurea at FPG <6 mmol/l Conventional glucose control therapy (mainly diet) UKPDS (n = 5,120) Lifetime 3.5% $3,400/QALY 
 Newly diagnosed type 2 diabetes Overweight Intensive glycemic control with metformin Conventional glucose control therapy (mainly diet)   Cost saving 
Eddy et al. 2005 (25) U.S. Newly diagnosed type 2 diabetes Intensive DPP lifestyle with FPG >125 mmol/l Target: A1C level of 7% ‡‡ Dietary advice DPP (n = 3,234) 30 years 3% $33,100/QALY 
    Almbrand et al. 2000 (13) Sweden Type 2 diabetes with acute MI Insulin-glucose infusion for at least 24 h, then subcutaneous multidose insulin for ≥3 months Standard antidiabetic therapy DIGAMI study, RCT 1-year intervention, 4-year follow-up (n = 620) 5 years** 3% $8,700/LYG, $12,400/QALY 
Self-monitoring blood glucose 
    Tunis 2008 (67) U.S. Type 2 diabetes treated with oral agents in a large HMO SMBG 1 time/day 40-year horizon public payer No SMBG Kaiser Permanente longitudinal study of cohort of “new antidiabetic drug users” 40 years 3% $8,200/QALY; 52.6% probability less than $50,000/QALY 
  SMBG 3 times/day 40-year horizon No SMBG   $6,900/QALY; 60.7% probability less than $50,000/QALY 
  SMBG 1 time/day 5-year horizon 10-year horizon No SMBG   $24,200/QALY
$9,700/QALY 
  SMBG 3 times/day 5-year horizon 10-year horizon No SMBG   $30,300/QALY
$540/QALY 
Intensive hypertension control 
    UKPDS 1998 (68) U.K. Type 2 diabetes Hypertension Tight control of hypertension, BP <150/<80 mmHg, ACE inhibitor, β-blocker, and other agents Less tight control of BP (mmHg), Initially <200/105, Later 180/105 UKPDS (n = 5,120) Lifetime 6% Cost saving in trial; $960/year free from occurrence of diabetes endpoint in clinic 
    Elliot et al. 2000 (26) U.S. Type 2 diabetes Hypertension, initially free of CVD or ESRD Reduction of BP to 130/85 mmHg Medications not mentioned Reduction of BP to 140/90 mmHg Meta-analysis of data from epidemiological studies and clinical trials Lifetime 3%  
 Start of treatment      
 Age 50 years     $1,200/LYG 
 Age 60 years     Cost saving 
 Age 70 years     Cost saving 
    Centers for Disease Control and Prevention 2002 (17) U.S. Type 2 diabetes Hypertension Intensified hypertension control ACE inhibitor β-blocker Average BP 144/82 mmHg Moderate hypertension control, Average BP 154/86 mmHg UKPDS (n = 5,120) Lifetime 3% Cost saving 
    Clarke et al. 2005 (19) U.K. Type 2 diabetes Hypertension Tight BP control BP <150/85 mmHg, ACE inhibitor (captopril) or β-blocker (atenolol) Less tight control of BP (mmHg), Initial <200/105, Later <180/105 UKPDS (n = 5,120) Lifetime 3.5% $200/QALY 
Cholesterol control 
    Herman et al. 1999 (33) U.S. Type 2 diabetes Dyslipidemia, Previous MI or angina Simvastatin Placebo 4S study, Double-blind randomized, placebo-controlled, multicenter, multicountry trial (n = 4,444) 5 years** 3% for cost, 0% for benefit Cost saving 
    Jonsson et al. 1999 (39) European countries Type 2 diabetes Dyslipidemia, Previous MI or angina Simvastatin Placebo 4S study (n = 4,444) Lifetime 3% CS-$9,400/LYG in different countries, Median: $2,800/LYG 
    Grover et al. 2000 (31) Canada Type 2 diabetes Dyslipidemia CVD history, Men and women 60 years old Simvastatin Placebo 4S study (n = 4,444) CARE (n = 4,159) Lifetime 5% $6,100–$12,300/LYG Increasing with pretreatment of LDL cholesterol level 
 Type 2 diabetes Dyslipidemia, No CVD history Simvastatin Placebo    
 Men Pretreatment LDL cholesterol level:      
 5.46 mmol/l (211 mg/dl)     $6,100–$15,000/LYG 
 3.5 mmol/l (135 mg/dl)     $10,700–$23,000/LYG 
 Women Pretreatment LDL cholesterol level:      
 5.46 mmol/l     $15,300–$27,600/LYG 
 3.5 mmol/l     $36,800–$61,300/LYG 
    Centers for Disease Control and Prevention 2002 (17) U.S. Type 2 diabetes Dyslipidemia, No CVD history Pravastatin Placebo West Scotland Coronary Prevention Study (n = 6,595 men) Lifetime 3% U-shape for age, $77,800/QALY 
    Raikou et al. 2007 (54) U.K. Ireland Type 2 diabetes, No CVD history, No elevated LDL cholesterol level ≥1 CVD risk factor: retinopathy, microalbuminuria or macroalbuminuria, current smoking, or hypertension Atorvastatin Placebo CARDS, Randomized, controlled, multicenter trial 94% white (n = 2,838) Lifetime 3.5% $2,800/LYG, $3,500/QALY Using UKPDS risk engine Low risk: $11,300/QALY; Medium risk: $4,700/QALY; High risk: $2,200/QALY 
Smoking cessation 
    Earnshaw et al. 2002 (23Newly diagnosed type 2 diabetes Smoking cessation, Standard antidiabetic care Standard antidiabetic care  Lifetime 3%  
        United States Smokers      
 Aged 25–84 years     <$25,000/QALY 
 Aged 85–94 years     $89,800/QALY 
Educational program 
    Shearer et al. 2004 (61)§ Germany Type 1 diabetes Structured treatment and teaching program: educational course of training to self-manage diabetes and enjoy dietary freedom Usual care (daily insulin injection) Rosiglitazone trial CODE2 study of prevalence of complications, not an RCT Lifetime 6% Cost saving 
    Gozzoli et al. 2001 (29) Switzerland Type 2 Standard antidiabetic care plus educational program, Self-monitoring, Recommendations on diet and exercise, Self-management of diabetes and complications, General health education Standard antidiabetic care Literature review (quality) Lifetime 3% $4,000/LYG 
Diabetes disease management 
    Mason et al. 2005 (43) England Type 2 diabetes Hypertension Policy to implement clinics led by specialist nurses to treat and control hypertension through consultation, medication review, condition assessment, and lifestyle advice Usual care SPLINT RCT (n = 1,407) UKPDS (n = 5,120) Lifetime 5% $4,800/QALY 
 Diagnosed diabetes Dyslipidemia Policy to implement clinics led by specialist nurses to treat and control hyperlipidemia by usual care Usual care   $23,600/QALY 
    Gilmer et al. 2007 (27) San Diego County, California Diabetes 48% Latinos Culturally sensitive case management and self-management training program led by bilingual/bicultural medical assistant and registered dietitian stepped-care pharmacologic management of glucose and lipid levels and hypertension‡‡‡ Standard care Project Dulce Observational cohort study with controls Average follow-up, 289 days (n = 3,893) 40 years 3% $9,400/LYG or $12,000/QALY for uninsured; 100% probability to be less than $50,000 and $100,000/QALY, respectively 
      $22,400/LYG or $29,100/QALY for patients in County Medical Services; 
      92% or 98% probability to be cost-effective if willingness to pay was $50,000 or $100,000/QALY, respectively 
      $42,600/LYG or $53,120/QALY for patients in Medi-Cal; 
      57% or 81% probability to be cost-effective if willingness to pay was $50,000 and $100,000/QALY, respectively 
      $68,400/LYG or $82,300/QALY for patients with commercial insurance; 
      31% and 62% probability to be cost-effective if willingness to pay was $50,000 and $100,000/QALY, respectively 
Preventing diabetic complications Eye complications 
    Javitt et al. 1994 (37)§ U.S. Newly diagnosed type 2 diabetes 8 strategies for eye screening with dilation: Screening every 1, 2, 3, or 4 years and No screening Cross-sectional and longitudinal studies Lifetime 5% All 8 strategies were cost saving 
  More frequent follow-up screening for diabetes patients with background retinopathy††     
Javitt et al. 1996 (38) U.S. Newly diagnosed type 1 and type 2 diabetes Annual eye screening with dilation for all patients with diabetes but no retinopathy Eye screening in 60% of diabetes patients Cross-sectional and longitudinal studies Lifetime 5% $3,800/person-year of sight saved, $6,900/QALY 
 Type 1 diabetes     $4,300/QALY 
 Type 2 diabetes Examination every 6 months for those with retinopathy    $6,900/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes Annual eye screening and treatment, Conventional insulin therapy Conventional insulin therapy Literature review Lifetime 3% Cost saving 
    Vijan et al. 2000 (69) U.S. Type 2 Eye screening for diabetes patients every 5 years Subsequent annual screening for those with background retinopathy No screening Epidemiological studies Lifetime 3% $23,500/QALY 
  Eye screening for diabetes patients every 3 years Subsequent annual screening for those with background retinopathy No screening   $27,000/QALY 
  Eye screening for diabetes patients every 2 years Subsequent annual screening for those with background retinopathy No screening   $30,700/QALY 
  Eye screening annually for diabetes patients Subsequent annual screening for those with background retinopathy No screening   $39,500/QALY 
  Eye screening for diabetes patients every 3 years 5-year intervals   $32,800/QALY 
  Eye screening for diabetes patients every 2 years 3-year intervals   $54,000/QALY 
  Annual eye screening for diabetes patients 2-year intervals   $116,800/QALY 
    Maberley et al. 2003 (42) Western James Bay, Victoria, British Columbia, Canada Type 1 diabetes and Type 2 diabetes Screening using digital camera Immediate assessment of quality or electronically transferred to a remote reading center Retina specialists visit Moose Factory every 6 months to examine people with diabetes, and patients in outlying communities are flown to Moose Factory, Canada  10 years 5% Cost saving 
Foot ulcers 
    Tennval et al. 2001 (64) Sweden Type 1 diabetes and Type 2 diabetes Optimal prevention of foot ulcer including foot inspection, appropriate footwear, treatment, and education Usual care Clinical and epidemiological data 5 years** 0%  
 High risk: Previous foot ulcer Previous amputation     Cost saving 
 Moderate risk: Neuropathy, PVD, and/or foot deformity     Cost saving 
 Low risk: No specific risk factor     >$100,000/QALY 
    Ortegon et al. 2004§ (45) The Netherlands Newly diagnosed type 2 diabetes Intensive glycemic control Optimal foot care Standard care UKPDS (n = 5,120) Lifetime 3% $44,900/QALY 
 Foot ulcer   Literature review on trials and epidemiological studies  Assuming 10% reduction of foot lesion, $308,300/QALY 
      Assuming 90% reduction of foot lesion, $17,000/QALY 
  Intensive glycemic control plus optimal foot care Standard care   Assuming 10% reduction of foot lesion, $34,400/QALY 
      Assuming 90% reduction of foot lesion, $11,010/QALY 
End-stage renal disease 
    Borch-Johnsen et al. 1993 (14)§ Germany Type 1 diabetes Annual screening for microalbuminuria at 5 years after diabetes onset, ACEI treatment Treatment of macroalbuminuria Danish cohort (n = 2,890) 30 years 6% Cost saving 
    Kiberd et al. 1996 (40)§ Canada Type 1 diabetes Screening for microalbuminuria ACEI treatment Treatment of hypertension and/or macroproteinuria Clinical trial Lifetime 5% $58,400/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes High total cholesterol level High systolic BP Microalbuminuria monitoring, ACE treatment, Conventional insulin therapy Conventional insulin therapy Literature review Lifetime 3% Cost saving 
    Dong et al. 2004 (22) U.S. Type 1 diabetes ACEI treatment starting at 1 year after diagnosis Annual screening for microalbuminuria ACE treatment DCCT (n = 1,441) Lifetime 3% $38,000/QALY, Increased with lowering A1C level; at A1C level 9%, <25,000/QALY 
    Sakthong et al. 2001 (57)§ Thailand Type 2 diabetes Microalbuminuria but normal BP ACE inhibitors Placebo 7-year RCT in Israel (n = 94) 25 years 8% Cost saving 
    Souchet et al. 2003 (62) France Type 2 diabetes Nephropathy Losartan Placebo RENAAL study Multicenter international trial (n = 1,513) 4 years** Cost discounted at 8% Benefits not discounted Cost saving 
    Szucs et al. 2004 (63)§ Switzerland Type 2 diabetes Nephropathy Losartan Placebo RENAAL study Multicenter international trial (n = 1,513) 3.5 years** 0% Cost saving 
    Palmer et al. 2003 (47) Belgium, France Type 2 diabetes Macroalbuminuria Hypertension Irbesartan Standard therapy for hypertension IDNT study Multicenter, double-blind placebo controlled trial (n = 1,715) Lifetime 3% Cost saving 
    Palmer et al. 2004 (49) U.K. Type 2 diabetes Hypertension Nephropathy Irbesartan Standard therapy for hypertension IDNT study (n = 1,715) 10 years 6% for costs 1.5% for benefits Cost saving 
    Palmer et al. 2005 (51) Spain Type 2 diabetes Microalbuminuria Hypertension Irbesartan Standard therapy for hypertension, No ACEI, AIIRA, or β-blockers IDNT study (n = 1,715) IRMA-2 trial Randomized controlled study (n = 582) 25 years 3% Cost saving 
    Palmer et al. 2007 (52) Hungary Type 2 diabetes Microalbuminuria Adding irbesartan Placebo + standard therapy for hypertension IDNT study (n = 1,715) IRMA-2 trial (n = 582) 25 years 5% Cost saving 
    Palmer et al. 2004 (48) U.S. Type 2 diabetes Hypertension Irbesartan at stage of microalbuminuria Standard therapy for hypertension IDNT study (n = 1,715) 25 years 3% Cost saving 
 Microalbuminuria Irbesartan at stage of macroalbuminuria Standard therapy for hypertension   Cost saving 
  Irbesartan at stage of microalbuminuria Irbesartan at stage of macroalbuminuria   Cost saving 
    Palmer et al. 2007 (53) U.K. Type 2 diabetes Hypertension Irbesartan at stage of microalbuminuria Standard therapy for hypertension IDNT study (n = 1,715) IRMA-2 trial (n = 582) 25 years 3.5% Cost saving 
 Microalbuminuria Irbesartan at stage of macroalbuminuria Standard therapy for hypertension   Cost saving 
  Irbesartan at stage of microalbuminuria Irbesartan at stage of macroalbuminuria   Cost saving 
    Coyle et al. 2007 (21) Canada Type 2 diabetes Hypertension Macronephropathy or Micronephropathy Irbesartan added at stage of microalbuminuria Conventional treatment for diabetes and hypertension, No ACEI or AIIRAs IDNT study (n = 1.715) IRMA-2 trial (n = 582) Lifetime 5% Cost saving 
  Irbesartan added at stage of overt nephropathy Conventional treatment for diabetes and hypertension   Cost saving 
  Irbesartan added at stage of microalbuminuria Irbesartan added at stage of overt nephropathy   Cost saving 
    Golan et al. 1999 (28) U.S. Newly diagnosed type 2 diabetes Treat patients with new diagnosis with ACEI Screening for macroalbuminuria and treatment with ACEI U.S.-Canada Collaborative study for type 1 diabetes, RCT (n = 207) 2 RCT for type 2 diabetes in Israel (n = 94 and 156, respectively) Lifetime 3% Cost saving 
  Screening for microalbuminuria and treatment with ACEI Screening for macroalbuminuria and treatment with ACEI   Cost saving 
  Treat patients with new diagnosis with ACEI Screening for microalbuminuria and treatment with ACEI   $10,900/QALY 
Clarke et al. 2000 (20) Canada Type 1 diabetes Province or territory paying for ACEI Pay from out-of-pocket Collaborative observational study using administrative data base (N=8.4 million) 21 years 5% Cost saving
Compliance rate and cost of ACEI affected ICER greatly 
Rosen et al. 2005 (55) US Medicare population Type 1 and type 2 diabetes Medicare full-payment for ACEI Pay from out-of-pocket HOPE Trial Lifetime 3% Cost saving if ACEI use increased by at least 7.2% 
  Medicare paying for ACEI Current Medicare Modernization Act Multinational RCT  If use increased by 2.9%, <$20,000/QALY 
      Cost saving if ACEI use increased by at least 6.2% 
      If use increased by 2.2%, <$20,000/QALY 
Comprehensive interventions 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes C + ACEI therapy + eye screening and treatment (EYE) Conventional glycemic control (C) Literature review Lifetime 3% Cost saving 
          Intensive insulin therapy (I) + ACEI therapy   $46,500/LYG 
  I + EYE   $50,600/LYG 
  I + ACEI therapy + EYE   $49,800/LYG 
    Gozzoli et al. 2001 (29) Switzerland Type 2 diabetes Added education program, nephropathy screening, and ACEI therapy to standard antidiabetic care Standard antidiabetic care Literature review Lifetime 0%, 3% Cost saving 
  Added education program, nephropathy screening, ACEI therapy, and retinopathy screening and laser therapy to standard antidiabetic care Standard antidiabetic care   Cost saving 
  Multifactorial intervention included educational program, screening for nephropathy and retinopathy, control of CVD risk factors, early diagnosis and treatment of complications, and health education Standard antidiabetic care   Cost saving 
Treatment of diabetes-related complications Retinopathy 
    Sharma et al. 2001 (60) U.S. Diabetic retinopathy Health maintenance organization Immediate vitrectomy for management of vitreous hemorrhage secondary to diabetic retinopathy Deferral of vitrectomy DRVS Lifetime 6% $2,900/QALY 
Foot ulcer 
    Habacher et al. 2007 (32) Austria Newly diagnosed diabetic foot ulcer Intensified treatment by international consensus on diabetic foot care Standard treatment Retrospective study of patient records on 119 consecutive ulcerations in 86 patients at tertiary outpatient clinic specializing in treatment of diabetic foot ulcers 15 years 0–8% Cost saving 
Source/study quality/countryStudy populationInterventionComparisonEffectiveness dataMethodology/analytical horizon/discount rateCost-effectiveness ratios (2007 U.S. $)
Preventing type 2 diabetes among high-risk individuals 
    Segal et al. 1998 (59)§ Australia Seriously obese or seriously obese with IGT Intensive diet and education Standard care Literature review 25 years 5% Cost saving 
 Overweight or obese IGT or NGT and IGT Group education in workplace on diet and physical activity for men Standard care   Cost saving 
 High-risk adults IGT or NGT and IGT General practitioner advice on healthy lifestyle Standard care   $1,000–$2,500/LYG 
 Overweight adults in general population Community-supported media campaign on obesity/sedentary lifestyle No campaign   Cost saving 
 Women with GDM history + NGT or IGT Intensive diet and behavioral modification Standard care   $1,300–$2,500/LYG 
    DPP 2003 (66) U.S. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) 3 years 0% $32,900/QALY; if in 10-person group, $11,100/QALY 
 IGT Metformin Standard advice on lifestyle   $134,000/QALY; if metformin cost reduced 50%, $76,500/QALY 
 IGT Intensive lifestyle modification‡‡ Standard advice on lifestyle   $69,400/QALY; if in 10-person group, $36,000/QALY 
 IGT Metformin‡‡ Standard advice on lifestyle   $133,400/QALY 
    Caro et al. 2004 (15) Canada IGT Intensive lifestyle modification No intervention DPP (n = 3,234), FDPS (n = 52) 10 years 5% $700/LYG 
IGT Metformin No intervention  Cost saving in LYG and QALY 
    Palmer et al. 2004 (50) Australia, France, Germany, Switzerland, U.K. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) Lifetime 5% except U.K.: cost 5%, effectiveness, 1.5% Cost saving except U.K.; U.K.: $8,300/LYG 
 IGT Metformin Standard advice on lifestyle   Cost saving, except UK; UK: $6,500/LYG 
    Eddy et al. 2005 (25) U.S. IGT Intensive lifestyle modification‡‡ No intervention DPP Multicenter RCT (n = 3,234) 30 years 3% $84,700/QALY; in 10-person group, $16,000/QALY 
 IGT Intensive lifestyle modification# No intervention   $192,600/QALY; in 10-person group, $36,400/QALY 
 IGT Metformin‡‡ No intervention   $47,900/QALY 
    Herman et al. 2005 (34) U.S. IGT Intensive lifestyle modification Standard advice on lifestyle DPP Multicenter RCT (n = 3,234) Lifetime 3% $1,500/QALY; in 10-person group, cost saving 
 Intensive lifestyle modification‡‡ Standard advice on lifestyle  $11,800/QALY 
  Metformin Standard advice on lifestyle   $42,000/QALY 
  Generic Standard advice on lifestyle   $2,400/QALY 
  Metformin‡‡    $40,200/QALY 
    Lindgren et al. 2007 (41) Sweden IGT Age 60 years BMI >25 kg/m2, FPG >6.1 mmol/l Intensive lifestyle intervention (6 years)‡‡ General lifestyle advice FDPS (n = 52) Lifetime 3% Cost saving not considering cost of extended life; $2,600/QALY including cost of extended life 
    Hoeger et al. 2007 (36) U.S. U.S. population age 45–74 years, overweight and obese (BMI ≥ 25 kg/m2) Groups Screening for IGT and IFPG, DPP lifestyle intervention with IGT + IFPG No screening and no lifestyle intervention DPP (n = 3,234) Lifetime 3% $10,600/QALY; in group settings, cost saving 
 Screening for IGT and IFPG, DPP lifestyle intervention with IFPG or IGT + IFPG No screening and lifestyle intervention   $12,300/QALY; in group settings, $344/QALY 
  Screening for IGT and IFPG, DPP lifestyle intervention with IGT + IFPG Screening for IGT and IFPG, following DPP lifestyle intervention with IFPG, IGT, or IFPG + IGT   $13,100/QALY 
  Screening and metformin treatment with IGT + IFPG No screening and treatment   $26,600/QALY 
  Screening and metformin treatment with IGT, IFPG, or IGT + IFPG No screening and treatment   $26,000/QALY 
Screening for undiagnosed type 2 diabetes and gestational diabetes 
    Centers for Disease Control and Prevention 1998 (16) U.S U.S. population 25 years and older One-time Opportunistic screening for undiagnosed type 2 diabetes starting at age 25 years, then treatment (universal screening) No screening and treatment until clinical diagnosis of type 2 diabetes  Lifetime 3% $374,900/LYG or $89,800/QALY; increasing with age (age ≥ 25 years) treatment (universal screening) 
     .      $57,100/LYG or $21,400/QALY (age 25–34 years) 
      $103,200/LYG or $29,700/QALY (age 35–44 years) 
      293,900/LYG or $70,100/QALY (age 45–54 years) 
      $1 million/LYG or $185,000/QALY (age 55–64 years) 
      $928,000/QALY (age ≥65) 
 African Americans:      
     age 25–34 years     $3,500/LYG or $1,300/QALY 
     age 35–44 years     $10,200/LYG or $3,100/QALY 
     age 45–54 years     $95,400/LYG or $19,600/QALY 
     age 55–64 years     $764,100/LYG or $112,600/QALY 
     age ≥65 years     $2 million/LYG or $500,000/QALY 
    Hoerger et al. 2004 (35) U.S. Persons with hypertension Targeted screening for undiagnosed diabetes among persons with hypertension No screening or treatment until clinical diagnosis of type 2 diabetes  Lifetime 3% $46,800–$130,500/QALY decreasing with age $70,500/QALY for age 45 years 
 U.S. population One-time opportunistic screening, then treatment (universal screening) No screening or treatment until clinical diagnosis of type 2 diabetes   $72,200–$189,100/QALY decreasing with age $183,500/QALY for age 45 years 
 U.S. population One-time opportunistic screening, then treatment (universal screening) Targeted screening, then treatment   $215,600–$699,800/QALY increasing with age 
    Nicolson et al. 2005 (44) U.S. 30-year-old pregnant women between 24–28 weeks' gestation Sequential method (50-g GCT + 100-g GTT)‡‡ No screening 75-g GTT A few unidentified RCTs <1 year** 0% Cost saving 
  100-g GTT‡‡ No screening or 75-g GTT method   Cost saving 
  100-g GTT‡‡ Sequential method   $35,200/QALY for maternal outcomes, $9,000/QALY for neonatal outcomes 
Intensive glycemic control 
    DCCT 1996 (65) U.S. Type 1 diabetes Intensive glycemic control through insulin management, self-monitoring, and outpatient visits. The goal was to achieve A1C level as normal as possible (6%) Conventional therapy (less intensive) DCCT Multicenter RCT (n = 1,441) Lifetime 3% $47,600/life year gained, $50,800/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes Intensive insulin therapy Conventional insulin therapy Literature review Lifetime 3%, 5%, 6% Reported results at 3% in the table $46,600/LYG 
    Scuffham et al. 2003 (58) U.K. Type 1 diabetes Continous subcutaneous insulin intervention for persons using insulin pump Multiple daily insulin injections 1 systematic review 1 meta-analysis 8 years 6% $10,200/QALY 
    Roze et al. 2005 (56) U.K. Type 1diabetes Continuous subcutaneous insulin infusion Multiple daily insulin injections DCCT (n = 1,441) mainly meta-analysis 60 years 3% $18,500/QALY 
    Eastman et al. 1997 (24) U.S. Newly diagnosed type 2 diabetes Intensive treatment targeting maintenance of A1C level at 7.2% Standard antidiabetic treatment targeting A1C level at 10% DCCT (n = 1,441) Lifetime 3% $17,400/QALY; sensitive to age at diabetes onset; CER <33,000 for age <50 years; $371,700/QALY for age 70–80 years 
    Gray et al. 2000 (30) U.K. Type 2 diabetes Intensive management with insulin or sulfonylurea aiming at FPG <6 mmol/l Conventional management (mainly through diet) aiming at FPG <15 mmol/l UKPDS Multicenter RCT (n = 5,120) 10 years** 6% Cost saving in trial; $1,100/event-free year gained in clinic setting 
    Wake et al. 2000 (70) Japan Type 2 diabetes Intensive insulin therapy through multiple insulin injections A1C <7% Conventional insulin injection therapy Kumamoto study RCT (n = 110) 10 years** 3% Cost saving 
    Clarke et al. 2001 (18) U.K. Newly diagnosed type 2 diabetes Overweight Intensive blood glucose control with metformin aiming at FPG <6 mmol/l Conventional treatment primarily with diet UKPDS (n = 5,120) Median 10.7 years** 6% Cost saving 
    Centers for Disease Control and Prevention 2002 (17) U.S. Newly diagnosed type 2 diabetes Intensive glycemic control with insulin or sulfonylurea aiming at FPG of 6 mmol/l Conventional glucose control (mainly diet) UKPDS (n = 5,120) Lifetime 3% $62,000/QALY; increasing rapidly with age at diagnosis: $14,400/QALY for age 25–34 years; $27,500–$56,000/QALY for age 35–54 years; > $100,000–$3.1 million for age 55–94 years 
      Cost saving under UKPDS cost scenario (no case management cost, much less self-testing, slightly fewer physician visits) but using U.S. unit cost 
    Clarke et al. 2005 (19) U.K. Newly diagnosed type 2 diabetes requiring insulin Intensive glycemic control with insulin or sulfonylurea at FPG <6 mmol/l Conventional glucose control therapy (mainly diet) UKPDS (n = 5,120) Lifetime 3.5% $3,400/QALY 
 Newly diagnosed type 2 diabetes Overweight Intensive glycemic control with metformin Conventional glucose control therapy (mainly diet)   Cost saving 
Eddy et al. 2005 (25) U.S. Newly diagnosed type 2 diabetes Intensive DPP lifestyle with FPG >125 mmol/l Target: A1C level of 7% ‡‡ Dietary advice DPP (n = 3,234) 30 years 3% $33,100/QALY 
    Almbrand et al. 2000 (13) Sweden Type 2 diabetes with acute MI Insulin-glucose infusion for at least 24 h, then subcutaneous multidose insulin for ≥3 months Standard antidiabetic therapy DIGAMI study, RCT 1-year intervention, 4-year follow-up (n = 620) 5 years** 3% $8,700/LYG, $12,400/QALY 
Self-monitoring blood glucose 
    Tunis 2008 (67) U.S. Type 2 diabetes treated with oral agents in a large HMO SMBG 1 time/day 40-year horizon public payer No SMBG Kaiser Permanente longitudinal study of cohort of “new antidiabetic drug users” 40 years 3% $8,200/QALY; 52.6% probability less than $50,000/QALY 
  SMBG 3 times/day 40-year horizon No SMBG   $6,900/QALY; 60.7% probability less than $50,000/QALY 
  SMBG 1 time/day 5-year horizon 10-year horizon No SMBG   $24,200/QALY
$9,700/QALY 
  SMBG 3 times/day 5-year horizon 10-year horizon No SMBG   $30,300/QALY
$540/QALY 
Intensive hypertension control 
    UKPDS 1998 (68) U.K. Type 2 diabetes Hypertension Tight control of hypertension, BP <150/<80 mmHg, ACE inhibitor, β-blocker, and other agents Less tight control of BP (mmHg), Initially <200/105, Later 180/105 UKPDS (n = 5,120) Lifetime 6% Cost saving in trial; $960/year free from occurrence of diabetes endpoint in clinic 
    Elliot et al. 2000 (26) U.S. Type 2 diabetes Hypertension, initially free of CVD or ESRD Reduction of BP to 130/85 mmHg Medications not mentioned Reduction of BP to 140/90 mmHg Meta-analysis of data from epidemiological studies and clinical trials Lifetime 3%  
 Start of treatment      
 Age 50 years     $1,200/LYG 
 Age 60 years     Cost saving 
 Age 70 years     Cost saving 
    Centers for Disease Control and Prevention 2002 (17) U.S. Type 2 diabetes Hypertension Intensified hypertension control ACE inhibitor β-blocker Average BP 144/82 mmHg Moderate hypertension control, Average BP 154/86 mmHg UKPDS (n = 5,120) Lifetime 3% Cost saving 
    Clarke et al. 2005 (19) U.K. Type 2 diabetes Hypertension Tight BP control BP <150/85 mmHg, ACE inhibitor (captopril) or β-blocker (atenolol) Less tight control of BP (mmHg), Initial <200/105, Later <180/105 UKPDS (n = 5,120) Lifetime 3.5% $200/QALY 
Cholesterol control 
    Herman et al. 1999 (33) U.S. Type 2 diabetes Dyslipidemia, Previous MI or angina Simvastatin Placebo 4S study, Double-blind randomized, placebo-controlled, multicenter, multicountry trial (n = 4,444) 5 years** 3% for cost, 0% for benefit Cost saving 
    Jonsson et al. 1999 (39) European countries Type 2 diabetes Dyslipidemia, Previous MI or angina Simvastatin Placebo 4S study (n = 4,444) Lifetime 3% CS-$9,400/LYG in different countries, Median: $2,800/LYG 
    Grover et al. 2000 (31) Canada Type 2 diabetes Dyslipidemia CVD history, Men and women 60 years old Simvastatin Placebo 4S study (n = 4,444) CARE (n = 4,159) Lifetime 5% $6,100–$12,300/LYG Increasing with pretreatment of LDL cholesterol level 
 Type 2 diabetes Dyslipidemia, No CVD history Simvastatin Placebo    
 Men Pretreatment LDL cholesterol level:      
 5.46 mmol/l (211 mg/dl)     $6,100–$15,000/LYG 
 3.5 mmol/l (135 mg/dl)     $10,700–$23,000/LYG 
 Women Pretreatment LDL cholesterol level:      
 5.46 mmol/l     $15,300–$27,600/LYG 
 3.5 mmol/l     $36,800–$61,300/LYG 
    Centers for Disease Control and Prevention 2002 (17) U.S. Type 2 diabetes Dyslipidemia, No CVD history Pravastatin Placebo West Scotland Coronary Prevention Study (n = 6,595 men) Lifetime 3% U-shape for age, $77,800/QALY 
    Raikou et al. 2007 (54) U.K. Ireland Type 2 diabetes, No CVD history, No elevated LDL cholesterol level ≥1 CVD risk factor: retinopathy, microalbuminuria or macroalbuminuria, current smoking, or hypertension Atorvastatin Placebo CARDS, Randomized, controlled, multicenter trial 94% white (n = 2,838) Lifetime 3.5% $2,800/LYG, $3,500/QALY Using UKPDS risk engine Low risk: $11,300/QALY; Medium risk: $4,700/QALY; High risk: $2,200/QALY 
Smoking cessation 
    Earnshaw et al. 2002 (23Newly diagnosed type 2 diabetes Smoking cessation, Standard antidiabetic care Standard antidiabetic care  Lifetime 3%  
        United States Smokers      
 Aged 25–84 years     <$25,000/QALY 
 Aged 85–94 years     $89,800/QALY 
Educational program 
    Shearer et al. 2004 (61)§ Germany Type 1 diabetes Structured treatment and teaching program: educational course of training to self-manage diabetes and enjoy dietary freedom Usual care (daily insulin injection) Rosiglitazone trial CODE2 study of prevalence of complications, not an RCT Lifetime 6% Cost saving 
    Gozzoli et al. 2001 (29) Switzerland Type 2 Standard antidiabetic care plus educational program, Self-monitoring, Recommendations on diet and exercise, Self-management of diabetes and complications, General health education Standard antidiabetic care Literature review (quality) Lifetime 3% $4,000/LYG 
Diabetes disease management 
    Mason et al. 2005 (43) England Type 2 diabetes Hypertension Policy to implement clinics led by specialist nurses to treat and control hypertension through consultation, medication review, condition assessment, and lifestyle advice Usual care SPLINT RCT (n = 1,407) UKPDS (n = 5,120) Lifetime 5% $4,800/QALY 
 Diagnosed diabetes Dyslipidemia Policy to implement clinics led by specialist nurses to treat and control hyperlipidemia by usual care Usual care   $23,600/QALY 
    Gilmer et al. 2007 (27) San Diego County, California Diabetes 48% Latinos Culturally sensitive case management and self-management training program led by bilingual/bicultural medical assistant and registered dietitian stepped-care pharmacologic management of glucose and lipid levels and hypertension‡‡‡ Standard care Project Dulce Observational cohort study with controls Average follow-up, 289 days (n = 3,893) 40 years 3% $9,400/LYG or $12,000/QALY for uninsured; 100% probability to be less than $50,000 and $100,000/QALY, respectively 
      $22,400/LYG or $29,100/QALY for patients in County Medical Services; 
      92% or 98% probability to be cost-effective if willingness to pay was $50,000 or $100,000/QALY, respectively 
      $42,600/LYG or $53,120/QALY for patients in Medi-Cal; 
      57% or 81% probability to be cost-effective if willingness to pay was $50,000 and $100,000/QALY, respectively 
      $68,400/LYG or $82,300/QALY for patients with commercial insurance; 
      31% and 62% probability to be cost-effective if willingness to pay was $50,000 and $100,000/QALY, respectively 
Preventing diabetic complications Eye complications 
    Javitt et al. 1994 (37)§ U.S. Newly diagnosed type 2 diabetes 8 strategies for eye screening with dilation: Screening every 1, 2, 3, or 4 years and No screening Cross-sectional and longitudinal studies Lifetime 5% All 8 strategies were cost saving 
  More frequent follow-up screening for diabetes patients with background retinopathy††     
Javitt et al. 1996 (38) U.S. Newly diagnosed type 1 and type 2 diabetes Annual eye screening with dilation for all patients with diabetes but no retinopathy Eye screening in 60% of diabetes patients Cross-sectional and longitudinal studies Lifetime 5% $3,800/person-year of sight saved, $6,900/QALY 
 Type 1 diabetes     $4,300/QALY 
 Type 2 diabetes Examination every 6 months for those with retinopathy    $6,900/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes Annual eye screening and treatment, Conventional insulin therapy Conventional insulin therapy Literature review Lifetime 3% Cost saving 
    Vijan et al. 2000 (69) U.S. Type 2 Eye screening for diabetes patients every 5 years Subsequent annual screening for those with background retinopathy No screening Epidemiological studies Lifetime 3% $23,500/QALY 
  Eye screening for diabetes patients every 3 years Subsequent annual screening for those with background retinopathy No screening   $27,000/QALY 
  Eye screening for diabetes patients every 2 years Subsequent annual screening for those with background retinopathy No screening   $30,700/QALY 
  Eye screening annually for diabetes patients Subsequent annual screening for those with background retinopathy No screening   $39,500/QALY 
  Eye screening for diabetes patients every 3 years 5-year intervals   $32,800/QALY 
  Eye screening for diabetes patients every 2 years 3-year intervals   $54,000/QALY 
  Annual eye screening for diabetes patients 2-year intervals   $116,800/QALY 
    Maberley et al. 2003 (42) Western James Bay, Victoria, British Columbia, Canada Type 1 diabetes and Type 2 diabetes Screening using digital camera Immediate assessment of quality or electronically transferred to a remote reading center Retina specialists visit Moose Factory every 6 months to examine people with diabetes, and patients in outlying communities are flown to Moose Factory, Canada  10 years 5% Cost saving 
Foot ulcers 
    Tennval et al. 2001 (64) Sweden Type 1 diabetes and Type 2 diabetes Optimal prevention of foot ulcer including foot inspection, appropriate footwear, treatment, and education Usual care Clinical and epidemiological data 5 years** 0%  
 High risk: Previous foot ulcer Previous amputation     Cost saving 
 Moderate risk: Neuropathy, PVD, and/or foot deformity     Cost saving 
 Low risk: No specific risk factor     >$100,000/QALY 
    Ortegon et al. 2004§ (45) The Netherlands Newly diagnosed type 2 diabetes Intensive glycemic control Optimal foot care Standard care UKPDS (n = 5,120) Lifetime 3% $44,900/QALY 
 Foot ulcer   Literature review on trials and epidemiological studies  Assuming 10% reduction of foot lesion, $308,300/QALY 
      Assuming 90% reduction of foot lesion, $17,000/QALY 
  Intensive glycemic control plus optimal foot care Standard care   Assuming 10% reduction of foot lesion, $34,400/QALY 
      Assuming 90% reduction of foot lesion, $11,010/QALY 
End-stage renal disease 
    Borch-Johnsen et al. 1993 (14)§ Germany Type 1 diabetes Annual screening for microalbuminuria at 5 years after diabetes onset, ACEI treatment Treatment of macroalbuminuria Danish cohort (n = 2,890) 30 years 6% Cost saving 
    Kiberd et al. 1996 (40)§ Canada Type 1 diabetes Screening for microalbuminuria ACEI treatment Treatment of hypertension and/or macroproteinuria Clinical trial Lifetime 5% $58,400/QALY 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes High total cholesterol level High systolic BP Microalbuminuria monitoring, ACE treatment, Conventional insulin therapy Conventional insulin therapy Literature review Lifetime 3% Cost saving 
    Dong et al. 2004 (22) U.S. Type 1 diabetes ACEI treatment starting at 1 year after diagnosis Annual screening for microalbuminuria ACE treatment DCCT (n = 1,441) Lifetime 3% $38,000/QALY, Increased with lowering A1C level; at A1C level 9%, <25,000/QALY 
    Sakthong et al. 2001 (57)§ Thailand Type 2 diabetes Microalbuminuria but normal BP ACE inhibitors Placebo 7-year RCT in Israel (n = 94) 25 years 8% Cost saving 
    Souchet et al. 2003 (62) France Type 2 diabetes Nephropathy Losartan Placebo RENAAL study Multicenter international trial (n = 1,513) 4 years** Cost discounted at 8% Benefits not discounted Cost saving 
    Szucs et al. 2004 (63)§ Switzerland Type 2 diabetes Nephropathy Losartan Placebo RENAAL study Multicenter international trial (n = 1,513) 3.5 years** 0% Cost saving 
    Palmer et al. 2003 (47) Belgium, France Type 2 diabetes Macroalbuminuria Hypertension Irbesartan Standard therapy for hypertension IDNT study Multicenter, double-blind placebo controlled trial (n = 1,715) Lifetime 3% Cost saving 
    Palmer et al. 2004 (49) U.K. Type 2 diabetes Hypertension Nephropathy Irbesartan Standard therapy for hypertension IDNT study (n = 1,715) 10 years 6% for costs 1.5% for benefits Cost saving 
    Palmer et al. 2005 (51) Spain Type 2 diabetes Microalbuminuria Hypertension Irbesartan Standard therapy for hypertension, No ACEI, AIIRA, or β-blockers IDNT study (n = 1,715) IRMA-2 trial Randomized controlled study (n = 582) 25 years 3% Cost saving 
    Palmer et al. 2007 (52) Hungary Type 2 diabetes Microalbuminuria Adding irbesartan Placebo + standard therapy for hypertension IDNT study (n = 1,715) IRMA-2 trial (n = 582) 25 years 5% Cost saving 
    Palmer et al. 2004 (48) U.S. Type 2 diabetes Hypertension Irbesartan at stage of microalbuminuria Standard therapy for hypertension IDNT study (n = 1,715) 25 years 3% Cost saving 
 Microalbuminuria Irbesartan at stage of macroalbuminuria Standard therapy for hypertension   Cost saving 
  Irbesartan at stage of microalbuminuria Irbesartan at stage of macroalbuminuria   Cost saving 
    Palmer et al. 2007 (53) U.K. Type 2 diabetes Hypertension Irbesartan at stage of microalbuminuria Standard therapy for hypertension IDNT study (n = 1,715) IRMA-2 trial (n = 582) 25 years 3.5% Cost saving 
 Microalbuminuria Irbesartan at stage of macroalbuminuria Standard therapy for hypertension   Cost saving 
  Irbesartan at stage of microalbuminuria Irbesartan at stage of macroalbuminuria   Cost saving 
    Coyle et al. 2007 (21) Canada Type 2 diabetes Hypertension Macronephropathy or Micronephropathy Irbesartan added at stage of microalbuminuria Conventional treatment for diabetes and hypertension, No ACEI or AIIRAs IDNT study (n = 1.715) IRMA-2 trial (n = 582) Lifetime 5% Cost saving 
  Irbesartan added at stage of overt nephropathy Conventional treatment for diabetes and hypertension   Cost saving 
  Irbesartan added at stage of microalbuminuria Irbesartan added at stage of overt nephropathy   Cost saving 
    Golan et al. 1999 (28) U.S. Newly diagnosed type 2 diabetes Treat patients with new diagnosis with ACEI Screening for macroalbuminuria and treatment with ACEI U.S.-Canada Collaborative study for type 1 diabetes, RCT (n = 207) 2 RCT for type 2 diabetes in Israel (n = 94 and 156, respectively) Lifetime 3% Cost saving 
  Screening for microalbuminuria and treatment with ACEI Screening for macroalbuminuria and treatment with ACEI   Cost saving 
  Treat patients with new diagnosis with ACEI Screening for microalbuminuria and treatment with ACEI   $10,900/QALY 
Clarke et al. 2000 (20) Canada Type 1 diabetes Province or territory paying for ACEI Pay from out-of-pocket Collaborative observational study using administrative data base (N=8.4 million) 21 years 5% Cost saving
Compliance rate and cost of ACEI affected ICER greatly 
Rosen et al. 2005 (55) US Medicare population Type 1 and type 2 diabetes Medicare full-payment for ACEI Pay from out-of-pocket HOPE Trial Lifetime 3% Cost saving if ACEI use increased by at least 7.2% 
  Medicare paying for ACEI Current Medicare Modernization Act Multinational RCT  If use increased by 2.9%, <$20,000/QALY 
      Cost saving if ACEI use increased by at least 6.2% 
      If use increased by 2.2%, <$20,000/QALY 
Comprehensive interventions 
    Palmer et al. 2000 (46) Switzerland Type 1 diabetes C + ACEI therapy + eye screening and treatment (EYE) Conventional glycemic control (C) Literature review Lifetime 3% Cost saving 
          Intensive insulin therapy (I) + ACEI therapy   $46,500/LYG 
  I + EYE   $50,600/LYG 
  I + ACEI therapy + EYE   $49,800/LYG 
    Gozzoli et al. 2001 (29) Switzerland Type 2 diabetes Added education program, nephropathy screening, and ACEI therapy to standard antidiabetic care Standard antidiabetic care Literature review Lifetime 0%, 3% Cost saving 
  Added education program, nephropathy screening, ACEI therapy, and retinopathy screening and laser therapy to standard antidiabetic care Standard antidiabetic care   Cost saving 
  Multifactorial intervention included educational program, screening for nephropathy and retinopathy, control of CVD risk factors, early diagnosis and treatment of complications, and health education Standard antidiabetic care   Cost saving 
Treatment of diabetes-related complications Retinopathy 
    Sharma et al. 2001 (60) U.S. Diabetic retinopathy Health maintenance organization Immediate vitrectomy for management of vitreous hemorrhage secondary to diabetic retinopathy Deferral of vitrectomy DRVS Lifetime 6% $2,900/QALY 
Foot ulcer 
    Habacher et al. 2007 (32) Austria Newly diagnosed diabetic foot ulcer Intensified treatment by international consensus on diabetic foot care Standard treatment Retrospective study of patient records on 119 consecutive ulcerations in 86 patients at tertiary outpatient clinic specializing in treatment of diabetic foot ulcers 15 years 0–8% Cost saving 

4S, Scandinavian Simvastatin Survival Study; ACEI, angiotensin converting enzyme inhibitors; AHT, arterial hypertension; AIIRA, angiotensin II receptor antagonists; BP, blood pressure; C, conventional glycemic control; CAD, coronary artery disease; CARDS, Collaborative Atorvastatin Diabetes Study; CARE, Cholesterol and Recurrent Events; CDC, Centers for Disease Control and Prevention; CODE2 = the cost of diabetes type 2 in Europe; CORE, Center for Outcomes Research; CVD, cardiovascular disease; DAIS, Diabetes Atherosclerosis Intervention Study; DCCT, Diabetes Control and Complications Trial; DIGAMI, Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction; DiGEM, diabetes glycemic education and monitoring; DPN, diabetic peripheral neuropathy; DPP, diabetes prevention program; DRVS, Diabetic Retinopathy Vitrectomy Study; DTTP, diabetes treatment and teaching program; EYE, screening for retinopathy and ensuing treatment; FDPS, Finish Diabetes Prevention Study; FPG, fasting plasma glucose; HMO, Health Maintenance Organization; HOPE, Heart Outcome Prevention Evaluation; I, intensive glycemic control; ICER, incremental cost effectiveness ratio; IDNT, Irbesartan Type II Diabetic Nephropathy Trial; IFPG, impaired fasting plasma glucose; IGT, impaired glucose tolerance; IMPACT, Improving Mood-Promoting Access to Collaborative Treatment; KORA, Cooperative Research in the Region of Augsburg; MI, myocardial infarction; NGT, normal glucose tolerance; NIDDM, Non-Insulin Dependent Diabetes Mellitus; OGTT, oral glucose tolerance test; PHN, postherpetic neuralgia; PROactive, PROspective pioglitAzone Clinical Trial in macroVascular Events; PROPHET, Prospective Population Health Event Tabulation; PVD, peripheral vascular disease; RCT, randomized clinical trial; RENAAL, Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; ROSSO, RetrOlective Study Self-Monitoring of Blood Glucose and Outcome; RPG, random plasma glucose; SMBG, self-monitoring blood glucose; SPECT, single proton emission computed tomography; SPLINT, specialist nurse-led intervention to treat and control hypertension and hyperlipidemia in diabetes; QALY, quality adjusted life year; VA-HIT, VA-HDL Intervention Trial.

*The studies were ordered by grouping similar interventions together, then follow the year and alphabetical order of the first author's last name; the numbers in the parenthesis are the reference number.

†The study was rated as “excellent” quality unless otherwise indicated.

§The study was rated as “good” quality.

‖The study is based on simulation modeling unless otherwise indicated.

**Within trial or within epidemiological study.

‡The study was done from the perspective of the health system unless otherwise indicated.

‡‡The study was done from the societal perspective.

#The study done from the perspective of the health plan.

††The study was done from the federal budget perspective.

†††Third party payer perspective.

Thirty-nine of the 56 studies took a long-term analytical time horizon, such as 20–30 years or lifetime. Nearly all of the studies with the long-term horizon used simulation modeling. Only one study was conducted in a developing country (Thailand) (57). There were 48 excellent studies and 8 good studies. Only three studies took perspectives other than the health care system.

The interventions evaluated in these CE studies covered a wide range: lifestyle and medication therapy to prevent type 2 diabetes among high-risk individuals (eight studies); screening for undiagnosed type 2 diabetes or GDM (three studies); intensive glycemic control (12 studies); self-monitoring of blood glucose (one study); intensive hypertension control (four studies); statin therapy for cholesterol control (five studies); smoking cessation (one study); diabetic health education program (two studies); diabetes disease management program (two studies); screening to prevent diabetic retinopathy (five studies); optimal foot care to prevent foot ulcer and amputation (two studies); ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy to prevent diabetic end-stage renal diseases (ESRD) (15 studies); comprehensive interventions using a combination of several of the above secondary prevention interventions (two studies); and interventions treating diabetic retinopathy and foot ulcers (two studies).

The classification of the interventions based on their level of CE and strength of evidence is presented in Table 2. For each intervention, we also described the number of studies that evaluated the CE of this intervention, its comparison intervention, and the study population in which the intervention was implemented. We reported the median and range of the ICERs across the studies.

Table 2

Summary of the cost-effectiveness studies by intervention*

InterventionComparisonIntervention populationNumber of studiesLevel of recommendation by ADAMedian of the cost-effectiveness ratiosRange of the cost-effectiveness ratios
Strong evidence 
Cost saving 
    ACEI therapy for intensive hypertension control Standard hypertension control Type 2 Cost saving Cost saving-$1,200/LYG $230/QALY 
    Addition of ACEI or ARB therapy to prevent ESRD No ACEI or ARB therapy Type 2 Cost saving Cost saving 
    Irbesartan therapy at the stage of microalbuminuria Irbestartan therapy at the stage of macroalbuminuria Type 2 Cost saving Cost saving 
    Comprehensive foot care to prevent ulcer Usual care Mixed population of type 1 and type 2 Cost saving Cost saving 
    Multi-component interventions (conventional insulin control, ACEI treatment, eye screening, and treatment) Conventional insulin control Type 1 A: ACEI treatment
B: eye screening and ensuing treatment 
Cost saving Cost saving 
    Multi-component interventions (standard antidiabetic care plus education, nephropathy screening, ACEI treatment, retinopathy screening) Standard antidiabetic care Type 2 B: education
E: nephropathy screening
B: ACEI therapy
B: retinopathy screening 
Cost saving Cost saving 
Very cost-effective 
    Intensive lifestyle modification Standard lifestyle recommendation or no intervention IGT B: medical nutritional therapy $1,500/QALY Cost saving-$84,700/QALY 
    A: physical activity   
    Universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old No screening African Americans aged 45–54 years $19,600/QALY $19,600/QALY 
    Intensive glycemic control as in UKPDS setting Conventional glycemic control Type 2 newly diagnosed A, B   
    $3,400/QALY Cost saving-$12,400/QALY  
    Statin therapy No statin therapy Type 2, with hyperlipidemia, with CVD history $2,800/LYG Cost saving-$12,300/LYG 
    Smoking cessation No smoking cessation Type 2 A, B <$25,000/QALY <$25,000/QALY-$89,800/QALY (aged 85–94 years) 
    Annual screening for diabetic retinopathy No screening Type 1 $2,150/QALY Cost saving-$4,300/QALY 
    Annual screening for diabetic retinopathy No screening Type 2 $6,900/QALY Cost saving-$39,500/QALY 
    Immediate vitrectomy to treat diabetic retinopathy Deferral of vitrectomy Mixed population of type 1 and type 2 Mentioned but not explicitly provided level, supported by trials $2,900/QALY $2,900/QALY 
Cost-effective 
    Targeted screening for undiagnosed type 2 diabetes No screening U.S. population with hypertension 45 years and older B: in adults of any age who are overweight or obese and who have one or more additional risk factors for diabetes. In those without these risk factors, testing should begin at age 45 $49,200/QALY $46,800–$70,500/QALY starting at different age 
    Intensive insulin treatment Conventional glycemic control Type 1 A, B $28,900/QALY $10,200–$50,800/QALY 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 newly diagnosed at 25–54 years old A, B $27,500/QALY $14,400-$56,000/QALY 
    Intensive glycemic control through lifestyle modification Conventional glycemic control Type 2 newly diagnosed A, B $33,100/QALY $33,100/QALY 
    Statin therapy No statin therapy Type 2, with hyperlipidemia, without CVD history A: statin therapy for diabetic patients without CVD who are older than 40 years and have one or more other CVD risk factors $38,200/LYG§ $6,100/LYG–$61,300/LYG $77,800/QALY 
    Multi-component interventions (intensive insulin control, ACEI treatment, eye screening and ensuing treatment) Intensive insulin control Type 1 A, B: intensive insulin control
A: ACEI therapy
B: eye screening 
$49,800/LYG (non U.S.) $46,500-$50,600/LYG 
Marginally cost-effective 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 newly diagnosed All age group diagnosed of diabetes at 25 years and older A, B $62,000/QALY $14,400–$3 million/QALY 
    Eye screening every 2 years Eye screening every 3 years Type 2 B: annual eye screening recommended, less frequent exams (every 2–3 years) may be considered following one or more normal eye exams $54,000/QALY $54,000/QALY 
Not cost-effective 
    Universal opportunistic screening for undiagnosed type 2 diabetes Targeted screening in persons with hypertension U.S. population 45 years and older >$100,000/QALY $70,100-$928,000/QALY 
    Universal opportunistic screening for undiagnosed type 2 diabetes and ensuing treatment No screening U.S. population 45 years and older >$100,000/QALY $70,100-$1 million 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 Newly diagnosed at 55–94 years A, B >$100,000/QALY >$100,000–$3 million/QALY 
    Eye screening every year Eye screening every 2 years Type 2 $116,800/QALY $116,800/QALY 
Supportive evidence 
Cost saving 
    Screening for GDM with sequential method No screening 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with 100-g GTT No screening 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with sequential method 75-g GTT 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with 100-g GTT 75-g GTT 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Diabetes self-management education No education Type 1 Cost saving Cost saving 
    Reimbursement for ACEI by public insurance Paying out-of-pocket Type 1 Cost saving Cost saving 
    Reimbursement for ACEI by public insurance Paying out-of-pocket Type 2 Cost saving Cost saving 
    Screening using mobile camera and electronically transmitted to a data reading center and read by trained personnel Retina-specialists visit Mixed population of type 1 and type 2 at a remote area Recommended but not leveled, assume level E Cost saving Cost saving 
    Screening for diabetic nephropathy and ensuing ACEI or ARB therapy Treat until macroalbuminuria Type 1 E: screening A: ACEI treatment Cost saving Cost saving-$58,400/QALY 
    Intensified foot ulcer treatment Standard treatment A mixed population of type 1 and type 2 Cost saving Cost saving 
Very cost-effective 
    Intensive diet and education Standard antidiabetic care Women with GDM history, currently IGT A, B $2,500/LYG $2,500/LYG 
    Universal opportunistic screening for type 2 diabetes in younger and certain ethnic groups No screening African Americans, aged 25–44 years B: if overweight or obese $3,100/QALY $1,300–$19,600/QALY 
    Screening for GDM 100-g GTT Sequential method 30-year-old pregnant women between 24–28 weeks' gestation $35,200/QALY for maternal outcomes, $9,000/QALY for neonatal outcomes $9,000–$35,200/QALY 
    Diabetes self-management education No education Type 2 $4,000/LYG $4,000/LYG 
    Disease management No disease management program Type 2 or mixed types Mentioned but not provided level, assume level E $23,350/QALY $4,800–$68,400/QALY for groups with different insurance 
    SMBG 3 times/day No SMBG Type 2 treated with oral agents in a large HMO $6,900/QALY $540–$30,300/QALY for different time horizon 
    SMBG 1 time/day No SMBG  $9,700/QALY $8,200–$24,200/QALY for different time horizon 
Cost-effective 
    Metformin Placebo IGT $26,600/QALY Cost saving-$47,900/QALY 
Marginally cost-effective 
        NA       
Not cost-effective 
        NA       
Uncertain 
    Optimal screening for type 2 diabetes starting age  U.S. population 45 years and older B: recommend starting screening for type 2 diabetes at age 45 years if no other risk factors   
InterventionComparisonIntervention populationNumber of studiesLevel of recommendation by ADAMedian of the cost-effectiveness ratiosRange of the cost-effectiveness ratios
Strong evidence 
Cost saving 
    ACEI therapy for intensive hypertension control Standard hypertension control Type 2 Cost saving Cost saving-$1,200/LYG $230/QALY 
    Addition of ACEI or ARB therapy to prevent ESRD No ACEI or ARB therapy Type 2 Cost saving Cost saving 
    Irbesartan therapy at the stage of microalbuminuria Irbestartan therapy at the stage of macroalbuminuria Type 2 Cost saving Cost saving 
    Comprehensive foot care to prevent ulcer Usual care Mixed population of type 1 and type 2 Cost saving Cost saving 
    Multi-component interventions (conventional insulin control, ACEI treatment, eye screening, and treatment) Conventional insulin control Type 1 A: ACEI treatment
B: eye screening and ensuing treatment 
Cost saving Cost saving 
    Multi-component interventions (standard antidiabetic care plus education, nephropathy screening, ACEI treatment, retinopathy screening) Standard antidiabetic care Type 2 B: education
E: nephropathy screening
B: ACEI therapy
B: retinopathy screening 
Cost saving Cost saving 
Very cost-effective 
    Intensive lifestyle modification Standard lifestyle recommendation or no intervention IGT B: medical nutritional therapy $1,500/QALY Cost saving-$84,700/QALY 
    A: physical activity   
    Universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old No screening African Americans aged 45–54 years $19,600/QALY $19,600/QALY 
    Intensive glycemic control as in UKPDS setting Conventional glycemic control Type 2 newly diagnosed A, B   
    $3,400/QALY Cost saving-$12,400/QALY  
    Statin therapy No statin therapy Type 2, with hyperlipidemia, with CVD history $2,800/LYG Cost saving-$12,300/LYG 
    Smoking cessation No smoking cessation Type 2 A, B <$25,000/QALY <$25,000/QALY-$89,800/QALY (aged 85–94 years) 
    Annual screening for diabetic retinopathy No screening Type 1 $2,150/QALY Cost saving-$4,300/QALY 
    Annual screening for diabetic retinopathy No screening Type 2 $6,900/QALY Cost saving-$39,500/QALY 
    Immediate vitrectomy to treat diabetic retinopathy Deferral of vitrectomy Mixed population of type 1 and type 2 Mentioned but not explicitly provided level, supported by trials $2,900/QALY $2,900/QALY 
Cost-effective 
    Targeted screening for undiagnosed type 2 diabetes No screening U.S. population with hypertension 45 years and older B: in adults of any age who are overweight or obese and who have one or more additional risk factors for diabetes. In those without these risk factors, testing should begin at age 45 $49,200/QALY $46,800–$70,500/QALY starting at different age 
    Intensive insulin treatment Conventional glycemic control Type 1 A, B $28,900/QALY $10,200–$50,800/QALY 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 newly diagnosed at 25–54 years old A, B $27,500/QALY $14,400-$56,000/QALY 
    Intensive glycemic control through lifestyle modification Conventional glycemic control Type 2 newly diagnosed A, B $33,100/QALY $33,100/QALY 
    Statin therapy No statin therapy Type 2, with hyperlipidemia, without CVD history A: statin therapy for diabetic patients without CVD who are older than 40 years and have one or more other CVD risk factors $38,200/LYG§ $6,100/LYG–$61,300/LYG $77,800/QALY 
    Multi-component interventions (intensive insulin control, ACEI treatment, eye screening and ensuing treatment) Intensive insulin control Type 1 A, B: intensive insulin control
A: ACEI therapy
B: eye screening 
$49,800/LYG (non U.S.) $46,500-$50,600/LYG 
Marginally cost-effective 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 newly diagnosed All age group diagnosed of diabetes at 25 years and older A, B $62,000/QALY $14,400–$3 million/QALY 
    Eye screening every 2 years Eye screening every 3 years Type 2 B: annual eye screening recommended, less frequent exams (every 2–3 years) may be considered following one or more normal eye exams $54,000/QALY $54,000/QALY 
Not cost-effective 
    Universal opportunistic screening for undiagnosed type 2 diabetes Targeted screening in persons with hypertension U.S. population 45 years and older >$100,000/QALY $70,100-$928,000/QALY 
    Universal opportunistic screening for undiagnosed type 2 diabetes and ensuing treatment No screening U.S. population 45 years and older >$100,000/QALY $70,100-$1 million 
    Intensive glycemic control as in the U.S. setting Conventional glycemic control Type 2 Newly diagnosed at 55–94 years A, B >$100,000/QALY >$100,000–$3 million/QALY 
    Eye screening every year Eye screening every 2 years Type 2 $116,800/QALY $116,800/QALY 
Supportive evidence 
Cost saving 
    Screening for GDM with sequential method No screening 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with 100-g GTT No screening 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with sequential method 75-g GTT 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Screening for GDM with 100-g GTT 75-g GTT 30-year-old pregnant women between 24–28 weeks' gestation Cost saving Cost saving 
    Diabetes self-management education No education Type 1 Cost saving Cost saving 
    Reimbursement for ACEI by public insurance Paying out-of-pocket Type 1 Cost saving Cost saving 
    Reimbursement for ACEI by public insurance Paying out-of-pocket Type 2 Cost saving Cost saving 
    Screening using mobile camera and electronically transmitted to a data reading center and read by trained personnel Retina-specialists visit Mixed population of type 1 and type 2 at a remote area Recommended but not leveled, assume level E Cost saving Cost saving 
    Screening for diabetic nephropathy and ensuing ACEI or ARB therapy Treat until macroalbuminuria Type 1 E: screening A: ACEI treatment Cost saving Cost saving-$58,400/QALY 
    Intensified foot ulcer treatment Standard treatment A mixed population of type 1 and type 2 Cost saving Cost saving 
Very cost-effective 
    Intensive diet and education Standard antidiabetic care Women with GDM history, currently IGT A, B $2,500/LYG $2,500/LYG 
    Universal opportunistic screening for type 2 diabetes in younger and certain ethnic groups No screening African Americans, aged 25–44 years B: if overweight or obese $3,100/QALY $1,300–$19,600/QALY 
    Screening for GDM 100-g GTT Sequential method 30-year-old pregnant women between 24–28 weeks' gestation $35,200/QALY for maternal outcomes, $9,000/QALY for neonatal outcomes $9,000–$35,200/QALY 
    Diabetes self-management education No education Type 2 $4,000/LYG $4,000/LYG 
    Disease management No disease management program Type 2 or mixed types Mentioned but not provided level, assume level E $23,350/QALY $4,800–$68,400/QALY for groups with different insurance 
    SMBG 3 times/day No SMBG Type 2 treated with oral agents in a large HMO $6,900/QALY $540–$30,300/QALY for different time horizon 
    SMBG 1 time/day No SMBG  $9,700/QALY $8,200–$24,200/QALY for different time horizon 
Cost-effective 
    Metformin Placebo IGT $26,600/QALY Cost saving-$47,900/QALY 
Marginally cost-effective 
        NA       
Not cost-effective 
        NA       
Uncertain 
    Optimal screening for type 2 diabetes starting age  U.S. population 45 years and older B: recommend starting screening for type 2 diabetes at age 45 years if no other risk factors   

ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker; CVD, cardiovascular disease; ESRD, end stage renal disease; GDM, gestational diabetes; GTT, glucose tolerance test; IGT, impaired glucose tolerance; LYG, life year gained; NA, not available; QALY, quality adjusted life years; SMBG, self-monitoring blood glucose. A, as defined in Standards of Medical Care in Diabetes—2008: clear evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered; compelling non-experimental evidence, i.e., “all or none” rule developed by the Centre for Evidence-Based Medicine at Oxford; supportive evidence from well-conducted randomized controlled trials that are adequately powered. B, as defined in Standards of Medical Care in Diabetes–2008: supportive evidence from well-conducted cohort studies; supportive evidence from a well-conducted case-control study. C, as defined in Standards of Medical Care in Diabetes–2008: supportive evidence from poorly controlled or uncontrolled studies; conflicting evidence with the weight of evidence supporting the recommendation. E, as defined in Standards of Medical Care in Diabetes–2008: expert consensus or clinical experience.

*, the same interventions applied to different populations or compared with different comparison interventions were treated as different specific interventions.

†, including foot exams, appropriate footwear, treatment, and education.

‡, the study for within trial and the results from health plan perspective are not used for determining the cost-effectiveness of the intervention.

§, get this number by taking the median for women in one study (conservative, women > men) as the results for that study, then take the median of the three study.

‖, 50-g GTT + 100-g GTT.

¶, the evidence was very weak: there was an over 40% probability that the intervention would cost more than $50,000/QALY in a long-term.

Twenty-six interventions were classified as supported by strong evidence concerning their CE (Table 2). Among these, six interventions were cost saving, eight were very cost-effective, six were cost-effective, two were marginally cost-effective, and four were not cost-effective. These interventions consisted of primary prevention, screening for undiagnosed type 2 diabetes, diabetic risk factor control, early prevention of diabetes complications, and treatment of diabetes complications.

The six cost-saving interventions with strong evidence were 1) ACEI therapy for intensive hypertension control, as in the UK Prospective Diabetes Study (UKPDS), in persons with type 2 diabetes compared with standard hypertension control; 2) ACEI or ARB therapy to prevent ESRD for type 2 diabetes compared with no ACEI or ARB therapy; 3) early irbesartan therapy at the stage of microalbuminuria to prevent ESRD in people with type 2 diabetes compared with treatment at the stage of macroalbuminuria; 4) comprehensive foot care to prevent ulcers in mixed population with either type 1 or type 2 diabetes compared with usual care; 5) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes.

Of the eight very cost-effective interventions with strong evidence, six were for persons with type 2 diabetes, one for persons with type 1 diabetes, and one for a mixed population with type 1 or type 2 diabetes. Interventions for type 2 diabetes included: 1) primary prevention through intensive lifestyle modification; 2) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3) intensive glycemic control as implemented in UKPDS; 4) statin therapy for secondary prevention of cardiovascular disease; 5) smoking cessation; and 6) annual screening for diabetic retinopathy and early treatment of it. The intervention for type 1 diabetes was annual screening for diabetic retinopathy and treating the positive cases. The intervention for mixed population of type 1 and type 2 diabetes was immediate vitrectomy to treat diabetic retinopathy compared with deferral of vitrectomy.

The six cost-effective interventions with strong evidence were 1) one-time opportunistic targeted screening for undiagnosed type 2 diabetes in hypertensive persons aged 45 years and older compared with no screening; 2) intensive insulin treatment for persons with type 1 diabetes compared with conventional glycemic control; 3) UKPDS-like intensive glycemic control applied to the U.S. health care system among adults younger than age 54 years with type 2 diabetes compared with conventional glycemic control; 4) intensive glycemic control by a Diabetes Prevention Program (DPP) type of intensive lifestyle intervention in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 5) statin therapy for primary prevention of cardiovascular disease in persons with type 2 diabetes compared with no statin therapy; 6) multi-component interventions including insulin therapy, ACEI therapy, and screening for retinopathy in persons with type 1 diabetes compared with intensive insulin therapy.

The two marginally cost-effective interventions with strong evidence were 1) intensive glycemic control for all U.S. residents with type 2 diabetes diagnosed at age 25 years and older compared with usual care; and 2) screening for diabetic retinopathy every two years compared with screening every three years in persons with type 2 diabetes.

The four interventions with strong evidence of not being cost-effective were 1) one-time universal opportunistic screening for undiagnosed type 2 diabetes among those aged 45 years and older compared with no screening; 2) universal screening for type 2 diabetes compared with targeted screening; 3) intensive glycemic control in the U.S. setting for patients diagnosed with diabetes at older ages (55–94 years of age) compared with usual care; and 4) annual screening for retinopathy compared with screening every two years. All these studies were for type 2 diabetes.

There were 18 specific interventions for which their CEs were based only on “supportive” evidence. Among them, 15 were each supported by one CE study, 13 were supported by level C or level E evidence, and five were supported by level A or B evidence as defined in the 2008 ADA standards of medical care in diabetes (7). For those interventions with level A or B evidence, the CE of each intervention was evaluated by one study with a quality of being “good.”

In terms of the level of the CE, 10 of the 18 specific interventions based on “supportive” evidence were cost-saving, including 1) screening using the sequential method (50-g glucose challenge test followed by 100-g glucose tolerance test [GTT]) for GDM in 30-year-old pregnant women between 24–28 weeks' gestation compared with no screening; 2) screening for GDM using the 100-g GTT method compared with no screening; 3) the sequential method compared with 75-g GTT screening for GDM; 4) 100-g GTT compared with 75-g GTT screening for GDM; 5) diabetes self-management education for persons with type 1 diabetes compared with no education; 6) full-reimbursement policy for ACEI for patients with type 1 diabetes compared with patients paying out-of-pocket; 7) full-reimbursement policy for ACEI for patients with type 2 diabetes compared with patients paying out-of-pocket; 8) screening using a mobile camera at a remote area and processing data in a reading center compared with a retina specialist's visit in a mixed population of type 1 and type 2 diabetes; 9) screening for diabetic nephropathy and ensuing ACEI or ARB therapy in persons with type 1 diabetes compared with no screening; and 10) intensified foot ulcer treatment in a mixed population with type 1 or type 2 diabetes compared with standard treatment.

Seven of the 18 specific interventions were very cost-effective: 1) primary prevention of type 2 diabetes in women with GDM history through intensive lifestyle intervention compared with usual care; 2) universal opportunistic screening for type 2 diabetes in African Americans aged 25–44 years compared with no screening; 3) 100-g GTT compared with the sequential screening method for detecting GDM in 30-year-old pregnant women between 24–28 weeks' gestation; 4) diabetes self-management education for persons with type 2 diabetes compared with no education; 5) disease management programs using specialist nurse–led clinics to treat and control hypertension or hyperlipidemia in patients with type 2 diabetes in a city in England or a culturally sensitive case–management training program to control diabetes and its risk factors in a Latino population with both type 1 and type 2 diabetes in a U.S. county compared with usual care only; 6) self-monitoring of blood glucose (SMBG) three times per day compared with no SMBG in type 2 noninsulin users; and 7) SMBG once per day compared with no SMBG in type 2 noninsulin users. One of the 18 specific interventions was cost-effective, i.e., the use of metformin to prevent type 2 diabetes in obese persons with impaired glucose tolerance compared with standard lifestyle intervention. No interventions in the “supportive” evidence category were “marginally cost-effective” or “not cost-effective.”

Current evidence is uncertain on how the CE of screening for undiagnosed type 2 diabetes would change with the age of those screened. Two studies evaluated the CE of screening for undiagnosed type 2 diabetes; one study reported that cost-effectiveness ratios (CERs) increased with initial screening age (16) while the other reported that they decreased with screening age (35).

Our systematic review showed that, with few exceptions, ADA-recommended interventions for preventing or treating diabetes and its complications were cost saving, very cost-effective, or cost-effective (i.e., with an ICER of less than $50,000 per QALY or LYG), although the strength of evidence varied. Generally, interventions that cost less than $50,000 per QALY are considered an efficient use of resources and worth recommending (11). Interventions with strong evidence for being cost saving, very cost-effective, or cost-effective should be considered for implementation. Interventions with supportive evidence for being cost saving, very cost-effective, or cost-effective should be adopted if extra resources are available or if similar interventions with strong evidence are unavailable or infeasible in a specific setting.

The one intervention recommended by the ADA that was shown as not CE was screening for type 2 diabetes of all U.S. residents aged 45 years and older. When considering allocating resources efficiently, universal screening for undiagnosed diabetes should be undertaken with great caution. The high CE ratio for universal screening for undiagnosed type 2 diabetes was primarily attributable to the small gain in health benefit. For example, screening everyone aged 45 years and older gained only 0.003 QALY per eligible person compared with no screening. However the additional costs associated with screening and early treatments were relatively large ($564 per person). Although detecting and treating diabetes earlier can prevent future diabetes-related complications and their associated medical costs, such savings are relatively small ($57 per person). Combining the health benefit and costs would yield an ICER of more than $1 million per QALY (35). An alternative to broad screening is to focus on screening persons with additional risk factors, such as hypertension. Such targeted screening is shown to be cost-effective when compared with no screening or universal screening.

Intensive glycemic control for all U.S. residents with type 2 diabetes diagnosed at age 25 years and older is marginally CE. However the cost-effectiveness of this intervention varies by age at the time of the diabetes diagnosis. The intervention is cost-effective in persons diagnosed at 25–54 years of age. However, intensive glycemic control for those diagnosed with diabetes at 55 years of age and older is not cost-effective. In fact, this result is consistent with the ADA's recommendation of less stringent A1C goals for patients with limited life expectancies.

The ADA recommended annual eye screening for diabetic retinopathy. This recommended intervention is very cost-effective compared with no screening in persons with type 2 diabetes. If considering the efficient allocation of resources, however, screening every other year might be a better alternative. Screening annually leads to a small health benefit but results in a moderate additional cost. For example, Vijan et al. (69) showed that, compared with a 2-year screening, annual screening among persons at moderate risk (65 years old with A1C level 9%) resulted in an increase of 2–3 days of sight at a cost of $540–690 per person. However the ADA also stated in its recommendation that “less frequent exams (every 2–3 years) may be considered following one or more normal eye exams.”

For the interventions with uncertain CE (including optimal age of starting screening for type 2 diabetes), following the current treatment guidelines may be the best option until more evidence on their CE is available.

The CEs of 43 ADA-recommended interventions were evaluated. Of these, 25 were in the “strong” evidence category. This number would probably have been larger if we had used less stringent criteria to define evidence as being strong. For example, evidence on the CE of using metformin to prevent type 2 diabetes among high-risk individuals was considered “supportive” in our current classification even though the efficacy of the intervention was shown by well-conducted multi-center large clinical trials in different country settings (71,72), and its CE was evaluated by “excellent” CE studies (25,34). This intervention was considered to have supportive evidence because it ranked lower in the ADA recommendations (7).

Among all the interventions considered, evidence for the CE of primary prevention through intensive lifestyle modification was the strongest regarding the quantity and quality of the CE studies and efficacy data. Several well-conducted clinical trials have shown the efficacy of intensive lifestyle modification in preventing diabetes in different country settings, such as the U.S. DPP (71), Finnish Diabetes Prevention Study (73), China Da Qing Diabetes Prevention Study (74), and Indian DPP (72). Eight cost-effectiveness studies (seven of them rated as excellent quality) have been conducted by different groups in different countries based on data from these well-conducted clinical trials (15,25,34,36,41,50,59,66). The results from these studies consistently showed that intensive lifestyle modification in persons with impaired glucose tolerance was cost saving or very cost-effective in the long run (15,25,34,36,41,50,59). Even in a short-term and one-on-one consulting setting, the intervention remained cost-effective (66). The intervention would be more cost-effective than existing studies show if the cost of the lifestyle intervention could be reduced. This might be achieved by changing the setting in which the intervention is provided. Only one study found a DPP-like intervention to be marginally cost-effective (25). Even in this study, however, the intervention would have been very cost-effective (23) if done in the type of group environment that is most likely in a real-world setting. A group-based, DPP-style lifestyle intervention partnership with the YMCA costs $275 to $325 per participant in the first year compared with $1,400 in the one-on-one setting of the DPP trial (75). Preventing diabetes, in particular by lifestyle modification, is not only effective but also a very efficient use of health care resources.

The CE of an intervention can vary by country setting. For example, intensive glycemic control (with a goal A1C level of 7%) in type 2 diabetic patients diagnosed at 25 years of age and older was marginally cost-effective in the U.S. but very cost-effective in other developed countries. Although the efficacy data of all studies of intensive glycemic control in type 2 diabetic patients were based on the same UKPDS data, the cost data were based on how residents of the different countries used health services and the cost of those services. The incremental cost of intensive glycemic control was much higher in the U.S. than in the U.K. because of different practice patterns. Patients outside the U.S. did not receive diabetes disease management services and had less frequent self-testing and physician office visits than their U.S. counterparts at the time these studies were conducted. If using the health services as described in the UKPDS setting but with the U.S. cost of these services, the CE of the intensive glycemic control in the U.S. would resemble that of other developed countries.

Future economic evaluation of diabetes interventions should consider the following. First, more studies are needed to evaluate the CE of interventions that fell in the “supportive” evidence category. For studies with weaker efficacy data, further efficacy studies are needed. Second, there are also 38 interventions recommended by the ADA but they have not been evaluated for their CE or the studies did not meet the inclusion criteria for our review (list is available upon request from the authors). The CE of these interventions should be assessed. Third, more CE studies are needed that address interventions in real-world settings. For example, few studies considered attrition rate, noncompliance, and dropout rates in evaluating CE. Fourth, more studies are needed to evaluate the CE of public policy changes. Only two studies evaluated public insurance reimbursement of ACEI therapy and both found this intervention to be cost saving. Finally, the CE of multiple interventions needs to be evaluated. In most real-world settings, patients receive multiple interventions simultaneously. Nearly all previous studies only evaluated the CE of a single intervention.

This review's conclusions should be used with caution. First, our conclusions are based on available information up to May 2008. More studies have been published since then. In addition, data on both the effectiveness and cost of an intervention could have changed since the time the original study was conducted. Using the newly available data could change our current conclusion. For example, in our review, we concluded that the CE of optimal age to start screening for type 2 diabetes was uncertain. A recently published CE study on age at initiation of screening for type 2 diabetes, released after our analysis was complete, might change that conclusion (76). Another example is the large decrease in costs for metformin, statins, and ACEIs. Studies that evaluate CE using current costs might look more favorably on interventions that include statins and ACEIs than those reported here. Reevaluating the costs and benefits of these interventions, using current-day costs, is beyond the scope of this study. Second, when using the results and conclusions of our review, readers need to be certain that terms are understood correctly. For example, “intensive insulin treatment” in our review meant “multiple insulin injection” or “insulin infusion.” Developments in medical technology might make continuous glucose monitoring systems, which record blood glucose levels throughout the day and night, more common. Drugs such as TZD Byetta and Gliptin, not available at the time covered by this review, are increasingly used to achieve intensive glycemic control. The CE of treatment with these and other new devices and drugs are unknown. New CE analyses are needed for these new interventions. Third, not everyone will necessarily agree with our classification criteria. Different classification criteria might have changed some conclusions. Fourth, most of the CE studies are based on simulation modeling. Although good-quality simulation modeling can provide information at a much lower cost than clinical trials, models are based on assumptions and represent a simplification of—and therefore might depart from—reality. Fifth, these CE studies use different methods, which could account for some differences in CERs. If the results from different models were consistent, we would have more confidence in the conclusion on the CE of the intervention. Sixth, we used the same threshold for the classification of the CE of interventions regardless of whether the ICERs were expressed as dollars per LYG or dollars per QALY, although they are different measures. The studies that reported costs per LYG did not incorporate the impact of the intervention on quality of life into the analysis. If they did, the cost per QALY could be higher, lower, or the same depending on the relative magnitude of the health benefit of the intervention on quality of life. Seventh, the interpretation of the CE of an intervention must include consideration of variables such as study population, comparison interventions, and country setting. Lastly, our recommendations are based on the CE of the interventions and not their efficacy; therefore, these recommendations are not necessarily the same as the ADA recommendations.

The importance of CE in decision making should not be overstated. CE is only one aspect to consider. CE analysis does not address the distribution of costs and the benefits of an intervention, societal or personal willingness to pay, social and legal aspects, or ethical issues associated with each intervention. All these aspects are important in formulating public policy. The good news is that our study shows that a majority of the recommended diabetes interventions provide both health benefits and good use of health care resources.

The findings and conclusions in this report are those of the authors and do not necessarily reflect the official positions of the Centers for Disease Control and Prevention.

The authors conducted this project as part of their jobs as employees of the Centers for Disease Control and Prevention (CDC). The CDC is a federal agency in the U.S. government. The authors have no financial interest in this project.

Parts of this study were presented at the 69th Scientific Sessions of the American Diabetes Association, New Orleans, Louisiana, 5–9 June 2009, and at the Division of Diabetes Translation 2007 Annual Conference, Atlanta, Georgia, April 30–May 3, 2007.

We thank Drs. Sue Kirkman, Richard Khan, William H. Herman, John Anderson, Susan Braithwaite, Dan Lorber, and Vivian Fonseca for reviewing the earlier version of this manuscript and providing valuable comments. We also thank Elizabeth Lee Greene for her invaluable editorial assistance.

1.
American Diabetes Association
.
Economic costs of diabetes in the U.S. in 2007
.
Diabetes Care
2008
;
31
:
1
20
2.
Klonoff
DC
,
Schwartz
DM
:
An economic analysis of interventions for diabetes
.
Diabetes Care
2000
;
23
:
390
404
3.
Raikou
M
,
McGuire
A
:
The economics of screening and treatment in type 2 diabetes mellitus
.
Pharmacoeconomics
2003
;
21
:
543
564
4.
Zhang
P
,
Engelgau
MM
,
Norris
SL
,
Gregg
EW
,
Narayan
KM
:
Application of economic analysis to Diabetes and Diabetes Care
.
Ann Intern Med
2004
;
140
:
972
977
5.
Vijgen
SM
,
Hoogendoorn
M
,
Baan
CA
,
de Wit
GA
,
Limburg
W
,
Feenstra
TL
:
Cost effectiveness of preventive interventions in type 2 diabetes mellitus: a systematic literature review
.
Pharmacoeconomics
2006
;
24
:
425
441
6.
Clarke
M
,
Oxman
AD
:
Cochrane Reviewers' Handbook
.
Oxford: updated software (October 2001)
,
Chichester, U.K.
,
John Wiley & Sons, Ltd
7.
American Diabetes Association
.
Standards of medical care in diabetes–2009
.
Diabetes Care
2008
;
31
(
Suppl. 1
):
S12
S54
8.
Drummond
MF
,
Jefferson
TO
:
Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party
.
BMJ
1996
;
313
:
275
283
9.
Federal Reserve Bank
.
Foreign Exchange Rates (annual) [Internet]
,
2008
. . Accessed 30 September 2008
10.
U.S. Department of Labor
.
Bureau of Labor Statistics: Consumer Price Index: achieved Consumer Price Index detailed report information: U.S. city average, by medical care [Internet]
,
2008
. . Accessed 30 September 2008
11.
Laupacis
A
,
Deeny
D
,
Detsky
AS
,
Tugwell
PX
:
How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations
.
Can Med Assoc J
1992
;
146
:
473
481
12.
Grosse
SD
:
Assessing cost-effectiveness in health care: history of the $50,000 per QALY threshold
.
Value Health
2008
;
8
:
165
178
13.
Almbrand
B
,
Johannesson
M
,
Sjostrand
B
,
Malmberg
K
,
Ryden
L
:
Cost-effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus; results from the DIGAMI study
.
Eur Heart J
2000
;
217
:
33
39
14.
Borch-Johnsen
K
,
Wenzel
H
,
Viberti
GC
,
Mogensen
CE
:
Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes?
BMJ
1993
;
306
:
1722
1725
15.
Caro
JJ
,
Getsios
D
,
Caro
I
,
Klittich
WS
,
O'Brien
JA
:
Economic evaluation of therapeutic interventions to prevent type 2 diabetes in Canada
.
Diabet Med
2004
;
21
:
1229
1236
16.
CDC Diabetes Cost-Effectiveness Study Group
.
The cost-effectiveness of screening for type 2 diabetes
.
JAMA
1998
;
280
:
1757
1763
17.
CDC Diabetes Cost-Effectiveness Group
.
Cost-effectiveness of intensive glycemic control, intensified hypertension control, and serum cholesterol level reduction for type 2 diabetes
.
JAMA
2002
;
287
:
2542
2551
18.
Clarke
P
,
Gray
A
,
Adler
A
,
Stevens
R
,
Raikou
M
,
Cull
C
,
Stratton
I
,
Holman
R
:
UKPDS Group
.
Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51)
.
Diabetologia
2001
;
44
:
298
304
19.
Clarke
PM
,
Gray
AM
,
Briggs
A
,
Stevens
RJ
,
Matthews
DR
,
Holman
RR
;
United Kingdom Prospective Diabetes Study
.
Cost-utility analyses of intensive blood glucose and tight blood pressure control in type 2 diabetes (UKPDS 72)
.
Diabetologia
2005
;
48
:
868
877
20.
Clarke
WF
,
Churchill
DN
,
Forwell
L
,
Macdonald
G
,
Foster
S
:
To pay or not to pay? A decision and cost-utility analysis of angiolensin-converting-enzyme inhibitor therapy for diabetic nephropathy
.
CMAJ Canadian Medical Association Journal
2000
;
162
:
195
198
21.
Coyle
D
,
Rodby
R
,
Soroka
S
,
Levin
A
,
Muirhead
N
,
de Cotret
PR
,
Chen
R
,
Palmer
A
:
Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective
.
Clinical Therapeutics
2007
;
29
:
1508
1523
22.
Dong
FB
,
Sorensen
SW
,
Manninen
DL
,
Thompson
TJ
,
Narayan
V
,
Orians
CE
,
Gregg
EW
,
Eastman
RC
,
Dasbach
EJ
,
Herman
WH
,
Newman
JM
,
Narva
AS
,
Ballard
DJ
,
Engelgau
MM
:
Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus
.
Pharmacoeconomics
2004
;
22
:
1015
1027
23.
Earnshaw
SR
,
Richter
A
,
Sorensen
SW
,
Hoerger
TJ
,
Hicks
KA
,
Engelgau
M
,
Thompson
T
,
Narayan
KM
,
Williamson
DF
,
Gregg
E
,
Zhang
P
:
Optimal allocation of resources across four interventions for type 2 diabetes
.
Med Decis Making
2002
;
22
(
Suppl. 5
):
S80
S91
24.
Eastman
RC
,
Javitt
JC
,
Herman
WH
,
Dasbach
EJ
,
Copley-Merriman
C
,
Maier
W
,
Dong
F
,
Manninen
D
,
Zbrozek
AS
,
Kotsanos
J
,
Garfield
SA
,
Harris
M
:
Model of complications of NIDDM: II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia
.
Diabetes Care
1997
;
20
:
735
744
25.
Eddy
DM
,
Schlessinger
L
,
Kahn
R
:
Clinical outcomes and cost-effectiveness of strategies for managing people at high risk for diabetes
.
Ann Intern Med
2005
;
143
:
251
264
26.
Elliott
WJ
,
Weir
DR
,
Black
HR
:
Cost-effectiveness of the lower treatment goal (of JNC VI) for diabetic hypertensive patients. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
.
Arch Intern Med
2000
;
160
:
1277
1283
27.
Gilmer
TP
,
Roze
S
,
Valentine
WJ
,
Emy-Albrecht
K
,
Ray
JA
,
Cobden
D
,
Nicklasson
L
,
Philis-Tsimikas
A
,
Palmer
AJ
:
Cost-effectiveness of diabetes case management for low-income populations
.
Health Services Research
2007
;
42
:
1943
1959
28.
Golan
L
,
Birkmeyer
JD
,
Welch
HG
:
The cost-effectiveness of treating all patients with type 2 diabetes with angiotensin-converting enzyme inhibitors
.
Ann Intern Med
1999
;
131
:
660
667
29.
Gozzoli
V
,
Palmer
AJ
,
Brandt
A
,
Spinas
GA
:
Economic and clinical impact of alternative disease management strategies for secondary prevention in type 2 diabetes in the Swiss setting
.
Swiss Med Wkly
2001
;
131
:
303
310
30.
Gray
A
,
Raikou
M
,
McGuire
A
,
Fenn
P
,
Stevens
R
,
Cull
C
,
Stratton
I
,
Adler
A
,
Holman
R
,
Turner
R
:
Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group
.
BMJ
2000
;
320
:
1373
1378
31.
Grover
SA
,
Coupal
L
,
Zowall
H
,
Dorais
M
:
Cost-effectiveness of treating hyperlipidemia in the presence of diabetes: who should be treated?
Circulation
2000
;
102
:
722
727
32.
Habacher
W
,
Rakovac
I
,
Görzer
E
,
Haas
W
,
Gfrerer
RJ
,
Wach
P
,
Pieber
TR
:
A model to analyse costs and benefit of intensified diabetic foot care in Austria
.
J Eval Clin Pract
2007
;
13
:
906
912
33.
Herman
WH
,
Alexander
CM
,
Cook
JR
,
Boccuzzi
SJ
,
Musliner
TA
,
Pedersen
TR
,
Kjekshus
J
,
Pyörälä
K
:
Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes: findings from the Scandinavian Simvastatin Survival Study
.
Diabetes Care
1999
;
22
:
1771
1778
34.
Herman
WH
,
Hoerger
TJ
,
Brandle
M
,
Hicks
K
,
Sorensen
S
,
Zhang
P
,
Hamman
RF
,
Ackermann
RT
,
Engelgau
MM
,
Ratner
RE
:
Diabetes Prevention Program Research Group
.
The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance
.
Ann Intern Med
2005
;
142
:
323
332
35.
Hoerger
TJ
,
Harris
R
,
Hicks
KA
,
Donahue
K
,
Sorensen
S
,
Engelgau
M
:
Screening for type 2 diabetes mellitus: a cost-effectiveness analysis
.
Ann Intern Med
2004
;
140
:
689
699
36.
Hoerger
TJ
,
Hicks
KA
,
Sorensen
SW
,
Herman
WH
,
Ratner
RE
,
Ackermann
RT
,
Zhang
P
,
Engelgau
MM
:
Cost-effectiveness of screening for pre-diabetes among overweight and obese U.S. adults
.
Diabetes Care
2007
;
30
:
2874
2879
37.
Javitt
JC
,
Aiello
LP
,
Chiang
Y
,
Ferris
FL
 3rd
,
Canner
JK
,
Greenfield
S
:
Preventive eye care in people with diabetes is cost-saving to the federal government: implications for health-care reform
.
Diabetes Care
1994
;
17
:
909
917
38.
Javitt
JC
,
Aiello
LP
:
Cost-effectiveness of detecting and treating diabetic retinopathy
.
Ann Intern Med
1996
;
124
:
164
169
39.
Jönsson
B
,
Cook
JR
,
Pedersen
TR
:
The cost-effectiveness of lipid lowering in patients with diabetes: results from the 4S trial
.
Diabetologia
1999
;
42
:
1293
1301
40.
Kiberd
BA
,
Jindal
KK
:
Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation
.
BMJ
1995
;
311
:
1595
1599
41.
Lindgren
P
,
Lindström
J
,
Tuomilehto
J
,
Uusitupa
M
,
Peltonen
M
,
Jönsson
B
,
de Faire
U
,
Hellénius
ML
:
DPS Study Group
.
Lifestyle intervention to prevent diabetes in men and women with impaired glucose tolerance is cost-effective
.
Int J Technol Assess Health Care
2007
;
23
:
177
183
42.
Maberley
D
,
Walker
H
,
Koushik
A
,
Cruess
A
:
Screening for diabetic retinopathy in James Bay, Ontario: a cost-effectiveness analysis
.
CMAJ
2003
;
168
:
160
164
43.
Mason
JM
,
Freemantle
N
,
Gibson
JM
,
New
JP
:
SPLINT trial
.
Specialist nurse-led clinics to improve control of hypertension and hyperlipidemia in diabetes: economic analysis of the SPLINT trial
.
Diabetes Care
2005
;
28
:
40
46
44.
Nicholson
WK
,
Fleisher
LA
,
Fox
HE
,
Powe
NR
:
Screening for gestational diabetes mellitus: a decision and cost-effectiveness analysis of four screening strategies
.
Diabetes Care
2005
;
28
:
1482
1484
45.
Ortegon
MM
,
Redekop
WK
,
Niessen
LW
:
Cost-effectiveness of prevention and treatment of the diabetic foot: a Markov analysis
.
Diabetes Care
2004
;
27
:
901
907
46.
Palmer
AJ
,
Weiss
C
,
Sendi
PP
,
Neeser
K
,
Brandt
A
,
Singh
G
,
Wenzel
H
,
Spinas
GA
:
The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective
.
Diabetologia
2000
;
43
:
13
26
47.
Palmer
AJ
,
Annemans
L
,
Roze
S
,
Lamotte
M
,
Rodby
RA
,
Cordonnier
DJ
:
An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings
.
Nephrol Dial Transplant
2003
;
18
:
2059
2066
48.
Palmer
AJ
,
Annemans
L
,
Roze
S
,
Lamotte
M
,
Lapuerta
P
,
Chen
R
,
Gabriel
S
,
Carita
P
,
Rodby
RA
,
de Zeeuw
D
,
Parving
HH
:
Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease
.
Diabetes Care
2004
;
27
:
1897
1903
49.
Palmer
AJ
,
Annemans
L
,
Roze
S
,
Lamotte
M
,
Rodby
RA
,
Bilous
RW
:
An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting
.
J Hum Hypertens
2004
;
18
:
733
738
50.
Palmer
AJ
,
Roze
S
,
Valentine
WJ
,
Spinas
GA
,
Shaw
JE
,
Zimmet
PZ
:
Intensive lifestyle changes or metformin in patients with impaired glucose tolerance: modeling the long-term health economic implications of the diabetes prevention program in Australia, France, Germany, Switzerland, and the United Kingdom
.
Clin Ther
2004
;
26
:
304
321
51.
Palmer
AJ
,
Annemans
L
,
Roze
S
,
Lapuerta
P
,
Chen
R
,
Gabriel
S
,
Carita
P
,
Rodby
RA
,
de Zeeuw
D
,
Parving
HH
,
De Alvaro
F
:
Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria
.
Kidney Int Suppl
2005
;
93
:
S52
S54
52.
Palmer
AJ
,
Valentine
WJ
,
Ray
JA
,
Roze
S
,
Muszbek
N
:
Health economic implications of irbesartan treatment versus standard blood pressure control in patients with type 2 diabetes, hypertension and renal disease: a Hungarian analysis
.
Eur J Health Econ
2007
;
8
:
161
168
53.
Palmer
AJ
,
Valentine
WJ
,
Ray
JA
:
Irbesartan treatment of patients with type 2 diabetes, hypertension and renal disease: a UK health economics analysis
.
Int J Clin Pract
2007
;
61
:
1626
1633
54.
Raikou
M
,
McGuire
A
,
Colhoun
HM
,
Betteridge
DJ
,
Durrington
PN
,
Hitman
GA
,
Neil
HA
,
Livingstone
SJ
,
Charlton-Menys
V
,
Fuller
JH
:
CARDS Investigators
.
Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS)
.
Diabetologia
2007
;
50
:
733
740
55.
Rosen
AB
,
Hamel
MB
,
Weinstein
MC
,
Cutler
DM
,
Fendrick
AM
,
Vijan
S
:
Cost-effectiveness of full medicare coverage of angiotensin-converting enzyme inhibitors for beneficiaries with diabetes
.
Annals of Internal Medicine
2005
;
143
:
89
99
56.
Roze
S
,
Valentine
WJ
,
Zakrzewska
KE
,
Palmer
AJ
:
Health-economic comparison of continuous subcutaneous insulin infusion with multiple daily injection for the treatment of type 1 diabetes in the UK
.
Diabet Med
2005
;
22
:
1239
1245
57.
Sakthong
P
,
Tangphao
O
,
Eiam-Ong
S
,
Kamolratanakul
P
,
Supakankunti
S
,
Himathongkam
T
,
Yathavong
K
:
Cost-effectiveness of using angiotensin-converting enzyme inhibitors to slow nephropathy in normotensive patients with diabetes type II and microalbuminuria
.
Nephrology
2001
;
6
:
71
77
58.
Scuffham
P
,
Carr
L
:
The cost-effectiveness of continuous subcutaneous insulin infusion compared with multiple daily injections for the management of diabetes
.
Diabet Med
2003
;
20
:
586
593
59.
Segal
L
,
Dalton
AC
,
Richardson
J
:
Cost-effectiveness of the primary prevention of non-insulin dependent diabetes mellitus
.
Health Promot Int
1998
;
13
:
197
209
60.
Sharma
S
,
Hollands
H
,
Brown
GC
,
Brown
MM
,
Shah
GK
,
Sharma
SM
:
The cost-effectiveness of early vitrectomy for the treatment of vitreous hemorrhage in diabetic retinopathy
.
Curr Opin Ophthalmol
2001
;
12
:
230
234
61.
Shearer
A
,
Bagust
A
,
Sanderson
D
,
Heller
S
,
Roberts
S
:
Cost-effectiveness of flexible intensive insulin management to enable dietary freedom in people with type 1 diabetes in the UK
.
Diabet Med
2004
;
21
:
460
467
62.
Souchet
T
,
Durand Zaleski
I
,
Hannedouche
T
,
Rodier
M
,
Gaugris
S
,
Passa
P
:
RENAAL study
.
An economic evaluation of Losartan therapy in type 2 diabetic patients with nephropathy: an analysis of the RENAAL study adapted to France
.
Diabete Metab
2003
;
29
:
29
35
63.
Szucs
TD
,
Sandoz
MS
,
Keusch
GW
:
The cost-effectiveness of losartan in type 2 diabetics with nephropathy in Switzerland: an analysis of the RENAAL study
.
Swiss Med Wkly
2004
;
134
:
440
447
64.
Tennvall
GR
,
Apelqvist
J
:
Prevention of diabetes-related foot ulcers and amputations: a cost-utility analysis based on Markov model simulations
.
Diabetologia
2001
;
44
:
2077
2087
65.
The DCCT Research Group
.
Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial
.
JAMA
1996
;
276
:
1409
1415
66.
Diabetes Prevention Program Research Group
.
Within-trial cost-effectiveness of lifestyle intervention or metformin for the primary prevention of type 2 diabetes
.
Diabetes Care
2003
;
26
:
2518
2523
67.
Tunis
SL
,
Minshall
ME
:
Self-monitoring of blood glucose in type 2 diabetes: cost-effectiveness in the United States
.
Am J Manag Care
2008
;
14
:
131
140
68.
UK Prospective Diabetes Study Group
.
Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40
.
BMJ
1998
;
317
:
720
726
69.
Vijan
S
,
Hofer
TP
,
Hayward
RA
:
Cost-utility analysis of screening intervals for diabetic retinopathy in patients with type 2 diabetes mellitus
.
JAMA
2000
;
283
:
889
896
70.
Wake
N
,
Hisashige
A
,
Katayama
T
,
Kishikawa
H
,
Ohkubo
Y
,
Sakai
M
,
Araki
E
,
Shichiri
M
:
Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year follow-up of the Kumamoto study
.
Diabetes Res Clin Pract
2000
;
48
:
201
210
71.
Knowler
WC
,
Barrett-Connor
E
,
Fowler
SE
,
Hamman
RF
,
Lachin
JM
,
Walker
EA
,
Nathan
DM
:
Diabetes Prevention Program Research Group
.
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
.
N Engl J Med
2002
;
346
:
393
403
72.
Ramachandran
A
,
Snehalatha
C
,
Mary
S
,
Mukesh
B
,
Bhaskar
AD
,
Vijay
V
:
Indian Diabetes Prevention Programme (IDPP)
.
The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1)
.
Diabetologia
2006
;
49
:
289
297
73.
Lindström
J
,
Louheranta
A
,
Mannelin
M
,
Rastas
M
,
Salminen
V
,
Eriksson
J
,
Uusitupa
M
,
Tuomilehto
J
:
Finnish Diabetes Prevention Study Group
.
The Finnish Diabetes Prevention Study (DPS): lifestyle intervention and 3-year results on diet and physical activity
.
Diabetes Care
2003
;
26
:
3230
3236
74.
Li
G
,
Zhang
P
,
Wang
J
,
Gregg
EW
,
Yang
W
,
Gong
Q
,
Li
H
,
Li
H
,
Jiang
Y
,
An
Y
,
Shuai
Y
,
Zhang
B
,
Zhang
J
,
Thompson
TJ
,
Gerzoff
RB
,
Roglic
G
,
Hu
Y
,
Bennett
PH
:
The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study
.
Lancet
2008
;
371
:
1783
1789
75.
Ackermann
RT
,
Marrero
DG
:
Adapting diabetes prevention program lifestyle intervention for delivery in the community
.
Diabetes Educ
2007
;
33
:
69
76.
Kahn
R
,
Alperin
P
,
Eddy
D
,
Borch-Johnsen
K
,
Buse
J
,
Feigelman
J
,
Gregg
E
,
Holman
RR
,
Kirkman
MS
,
Stern
M
,
Tuomilehto
J
,
Wareham
NJ
:
Age at initiation and frequency of screening to detect type 2 diabetes: a cost-effectiveness analysis
.
Lancet
2010
;
375
:
1324
1326