Twenty-seven published randomized controlled trials (RCTs) assessing outcomes of continuous glucose monitoring (CGM), involving a total of 3,826 patients, have been published to date. Although the number of patients in each study has been small compared to drug trials, cumulative evidence indicates a benefit of CGM for patients treated with either continuous subcutaneous insulin infusion (CSII) or a multiple daily injection (MDI) insulin regimen. Additionally, some data suggest that CGM may benefit people with type 2 diabetes who do not use insulin therapy.
Overall, RCTs have shown improved glucose control in patients with higher initial A1Cs (often in the range of 7.8–8.8%) using CGM compared to self-monitoring of blood glucose (SMBG). People who wear their CGM device most consistently derive the most benefit. Time spent in the designated hypoglycemia range (usually <70 mg/dL) was reduced in some studies, particularly in those with patients selected for having a higher risk of hypoglycemia. These patients tended to have lower baseline A1Cs (in the range of 6.5–7.5%). Rates of severe hypoglycemia generally have not differed between CGM and non-CGM groups, and these rates have been low across all studies.
Studies fall into a few basic categories: adults with type 1 diabetes (8 trials, 698 patients), adults with type 2 diabetes (4 trials, 547 patients), children with type 1 diabetes (2 trials, 227 patients), adults plus children with type 1 diabetes (7 trials, 1,084 patients), adults with type 1 or type 2 diabetes (3 trials, 655 patients), and women during pregnancy with either type 1 diabetes or gestational diabetes mellitus (GDM) (3 trials, 585 patients). Table 1 lists general findings from all of these trials. It is important to note that some trials used A1C or time in range as the primary endpoint, whereas others used time in a hypoglycemic range as the primary outcome. Readers should also be aware that Table 1 is not a meta-analysis per se, but rather includes studies identified through a literature search of PubMed and Ovid MEDLINE, as well as all prior reviews and studies in their reference lists. Only RCT data are included; observational studies and extension phases of RCTs also have been performed but are not represented here.
Summary of CGM Research Studies
| Study . | Design . | Primary Outcome/Type of CGM . | A1C Outcomes . | Hypoglycemia Change/Other . |
|---|---|---|---|---|
| ADULTS WITH T1D: A1C PRIMARY OUTCOME | ||||
| Beck et al. (1,2) |
| A1C reduction / Dexcom G4 Platinum | –0.6%, P <0.001 |
|
| Lind et al. (3) |
| A1C reduction / Dexcom G4 Platinum | –0.43, P <0.001 |
|
| Sequeira et al. (4) |
| A1C reduction / Dexcom SEVEN | No significant difference between groups |
|
| Tumminia et al. (5) |
| A1C reduction / Medtronic Guardian REAL-Time | Only analyzed 14 patients who used CGM ≥40% of the time; in these patients, there was a significant reduction in A1C (P <0.05) | Risk for hypoglycemia was reduced (time spent <70 mg/dL/ day), P <0.05 |
| ADULTS WITH T1D: HYPOGLYCEMIA PRIMARY OUTCOME | ||||
| Bolinder et al. (6) |
| Change in time in hypoglycemic range (<70 mg/dL) / Abbott FreeStyle Libre | NS |
|
| Hermanns et al. (7) |
| Proportion of time spent hypoglycemic / Dexcom SEVEN PLUS | N/A |
|
| van Beers et al. (8) |
| Mean difference in time in range (4–10 mmol/L [72–180 mg/dL]) / Medtronic Enlite with a MiniMed Paradigm Veo system (used as a monitor) | NS |
|
| ADULTS AND CHILDREN WITH T1D: A1C/TIME IN RANGE PRIMARY OUTCOME | ||||
| Battelino et al. (9) |
| A1C reduction / Medtronic Guardian REAL-Time | A1C difference –0.43% in favor of sensor on, P <0.001 |
|
| Deiss et al. (10) |
| A1C reduction / Medtronic Guardian REAL-Time | Arm 1: –0.6%, P = 0.003; Arm 2: no difference in A1C | One episode of severe hypoglycemia in each arm |
| JDRF CGM Study Group (11) |
| A1C reduction / DexCom SEVEN, Medtronic MiniMed Paradigm REAL-Time insulin pump and CGMS, and Abbott FreeStyle Navigator |
| No difference in time spent in a hypoglycemic range or in number of severe hypoglycemic episodes |
| O’Connell et al. (12) |
| Time in range during the 3-month study period / Medtronic MiniMed Paradigm REAL-Time insulin pump and CGMS |
| No difference in time in range, variability, or hypoglycemia |
| ADULTS AND CHILDREN WITH T1D: HYPOGLYCEMIA PRIMARY OUTCOME | ||||
| JDRF CGM Study Group (13) |
| Change in time ≤70 mg/dL / DexCom SEVEN, MiniMed Paradigm REAL-Time insulin pump and CGMS, and Abbott FreeStyle Navigator | A1C treatment difference favoring CGM, P <0.001 |
|
| Battelino et al. (14) |
| Time spent in hypoglycemic range / Abbott FreeStyle Navigator | A1C treatment difference favoring CGM: –0.27%, P = 0.008 |
|
| Heinemann et al. (15) |
| Baseline-adjusted hypoglycemia events (glucose ≤3.0 mmol/L [54 mg/dL] for ≥20 minutes) / Dexcom G5 Mobile | No difference in A1C | Adjusted between-group difference in low glucose events: 0.28, P <0.0001 |
| CHILDREN WITH T1D | ||||
| Ludvigsson et al. (16) |
| A1C reduction/ Medtronic CGMS | A1C difference at 12 weeks during open vs. blind CGM: ∼–0.39%, P = 0.011 | No significant differences in hypoglycemia |
| Chase et al. (17) |
| A1C reduction / GlucoWatch G2 Biographer | No significant change in A1C | Sensor use declined from 2.1 to 1.5 times/week because of skin irritation and other issues |
| ADULTS WITH T2D | ||||
| Beck et al. (18) |
| A1C reduction / Dexcom G4 Platinum with an enhanced algorithm | Adjusted mean A1C difference: –0.3%, P = 0.022 | No change in hypoglycemia |
| Ehrhardt et al. (19) |
| A1C reduction / Dexcom SEVEN | Difference in A1C: –0.6%, P = 0.002 |
|
| Haak et al. (20) |
| A1C reduction / Abbott FreeStyle Libre | No difference in A1C overall; difference in A1C if <65 years of age, P = 0.03 | Time in hypoglycemia (<70 mg/dL) was reduced by 43%, P = 0.0006 |
| Yoo et al. (21) |
| A1C reduction / Medtronic Guardian REAL-Time | Improvement in A1C greater in CGM group, ∼0.5%, P = 0.004 (CGM: from 9.1 ± 1.0 to 8.0 ± 1.2%, P <0.001; SMBG: from 8.7 ± 0.7 to 8.3 ± 1.1%, P = 0.01) |
|
| ADULTS WITH T1D OR T2D | ||||
| Garg et al. (22) |
| Time spent in high, low, and target glucose zones / Dexcom STS sensor |
| CGM group spent 21% less time in hypoglycemia (<55 mg/dL), P <0.0001 |
| New et al. (23) |
| Time spent outside of target range / Abbott FreeStyle Navigator; 1/3 CGM with no alarm, 1/3 CGM with alarm, 1/3 SMBG | No difference in A1C or time spent outside of target range | Less time in hypoglycemia range in group with alarms compared to SMBG group, P = 0.03 |
| Cooke et al. (24) |
| A1C reduction / GlucoWatch G2 Biographer vs. Medtronic MiniMed CGMS (blinded) | No significant difference in A1C reduction | No reduction in hypoglycemia; possibly an increase |
| PREGNANT PATIENTS WITH T1D, T2D, OR GDM | ||||
| Feig et al. (25) |
| A1C reduction / Medtronic Guardian REAL-Time or MiniMed MiniLink | A1C difference –0.19%, P = 0.0207 in pregnant women; no A1C difference in\ women planning pregnancy |
|
| Secher et al. (26) |
| LGA babies / Medtronic Guardian REAL-time CGM with Sof-Sensor | No difference in A1C |
|
| Wei et al.(27) |
| Prenatal or obstetrical outcomes / Medtronic Gold CGMS | No significant reduction in A1C |
|
| Study . | Design . | Primary Outcome/Type of CGM . | A1C Outcomes . | Hypoglycemia Change/Other . |
|---|---|---|---|---|
| ADULTS WITH T1D: A1C PRIMARY OUTCOME | ||||
| Beck et al. (1,2) |
| A1C reduction / Dexcom G4 Platinum | –0.6%, P <0.001 |
|
| Lind et al. (3) |
| A1C reduction / Dexcom G4 Platinum | –0.43, P <0.001 |
|
| Sequeira et al. (4) |
| A1C reduction / Dexcom SEVEN | No significant difference between groups |
|
| Tumminia et al. (5) |
| A1C reduction / Medtronic Guardian REAL-Time | Only analyzed 14 patients who used CGM ≥40% of the time; in these patients, there was a significant reduction in A1C (P <0.05) | Risk for hypoglycemia was reduced (time spent <70 mg/dL/ day), P <0.05 |
| ADULTS WITH T1D: HYPOGLYCEMIA PRIMARY OUTCOME | ||||
| Bolinder et al. (6) |
| Change in time in hypoglycemic range (<70 mg/dL) / Abbott FreeStyle Libre | NS |
|
| Hermanns et al. (7) |
| Proportion of time spent hypoglycemic / Dexcom SEVEN PLUS | N/A |
|
| van Beers et al. (8) |
| Mean difference in time in range (4–10 mmol/L [72–180 mg/dL]) / Medtronic Enlite with a MiniMed Paradigm Veo system (used as a monitor) | NS |
|
| ADULTS AND CHILDREN WITH T1D: A1C/TIME IN RANGE PRIMARY OUTCOME | ||||
| Battelino et al. (9) |
| A1C reduction / Medtronic Guardian REAL-Time | A1C difference –0.43% in favor of sensor on, P <0.001 |
|
| Deiss et al. (10) |
| A1C reduction / Medtronic Guardian REAL-Time | Arm 1: –0.6%, P = 0.003; Arm 2: no difference in A1C | One episode of severe hypoglycemia in each arm |
| JDRF CGM Study Group (11) |
| A1C reduction / DexCom SEVEN, Medtronic MiniMed Paradigm REAL-Time insulin pump and CGMS, and Abbott FreeStyle Navigator |
| No difference in time spent in a hypoglycemic range or in number of severe hypoglycemic episodes |
| O’Connell et al. (12) |
| Time in range during the 3-month study period / Medtronic MiniMed Paradigm REAL-Time insulin pump and CGMS |
| No difference in time in range, variability, or hypoglycemia |
| ADULTS AND CHILDREN WITH T1D: HYPOGLYCEMIA PRIMARY OUTCOME | ||||
| JDRF CGM Study Group (13) |
| Change in time ≤70 mg/dL / DexCom SEVEN, MiniMed Paradigm REAL-Time insulin pump and CGMS, and Abbott FreeStyle Navigator | A1C treatment difference favoring CGM, P <0.001 |
|
| Battelino et al. (14) |
| Time spent in hypoglycemic range / Abbott FreeStyle Navigator | A1C treatment difference favoring CGM: –0.27%, P = 0.008 |
|
| Heinemann et al. (15) |
| Baseline-adjusted hypoglycemia events (glucose ≤3.0 mmol/L [54 mg/dL] for ≥20 minutes) / Dexcom G5 Mobile | No difference in A1C | Adjusted between-group difference in low glucose events: 0.28, P <0.0001 |
| CHILDREN WITH T1D | ||||
| Ludvigsson et al. (16) |
| A1C reduction/ Medtronic CGMS | A1C difference at 12 weeks during open vs. blind CGM: ∼–0.39%, P = 0.011 | No significant differences in hypoglycemia |
| Chase et al. (17) |
| A1C reduction / GlucoWatch G2 Biographer | No significant change in A1C | Sensor use declined from 2.1 to 1.5 times/week because of skin irritation and other issues |
| ADULTS WITH T2D | ||||
| Beck et al. (18) |
| A1C reduction / Dexcom G4 Platinum with an enhanced algorithm | Adjusted mean A1C difference: –0.3%, P = 0.022 | No change in hypoglycemia |
| Ehrhardt et al. (19) |
| A1C reduction / Dexcom SEVEN | Difference in A1C: –0.6%, P = 0.002 |
|
| Haak et al. (20) |
| A1C reduction / Abbott FreeStyle Libre | No difference in A1C overall; difference in A1C if <65 years of age, P = 0.03 | Time in hypoglycemia (<70 mg/dL) was reduced by 43%, P = 0.0006 |
| Yoo et al. (21) |
| A1C reduction / Medtronic Guardian REAL-Time | Improvement in A1C greater in CGM group, ∼0.5%, P = 0.004 (CGM: from 9.1 ± 1.0 to 8.0 ± 1.2%, P <0.001; SMBG: from 8.7 ± 0.7 to 8.3 ± 1.1%, P = 0.01) |
|
| ADULTS WITH T1D OR T2D | ||||
| Garg et al. (22) |
| Time spent in high, low, and target glucose zones / Dexcom STS sensor |
| CGM group spent 21% less time in hypoglycemia (<55 mg/dL), P <0.0001 |
| New et al. (23) |
| Time spent outside of target range / Abbott FreeStyle Navigator; 1/3 CGM with no alarm, 1/3 CGM with alarm, 1/3 SMBG | No difference in A1C or time spent outside of target range | Less time in hypoglycemia range in group with alarms compared to SMBG group, P = 0.03 |
| Cooke et al. (24) |
| A1C reduction / GlucoWatch G2 Biographer vs. Medtronic MiniMed CGMS (blinded) | No significant difference in A1C reduction | No reduction in hypoglycemia; possibly an increase |
| PREGNANT PATIENTS WITH T1D, T2D, OR GDM | ||||
| Feig et al. (25) |
| A1C reduction / Medtronic Guardian REAL-Time or MiniMed MiniLink | A1C difference –0.19%, P = 0.0207 in pregnant women; no A1C difference in\ women planning pregnancy |
|
| Secher et al. (26) |
| LGA babies / Medtronic Guardian REAL-time CGM with Sof-Sensor | No difference in A1C |
|
| Wei et al.(27) |
| Prenatal or obstetrical outcomes / Medtronic Gold CGMS | No significant reduction in A1C |
|
JDRF, Juvenile Diabetes Research Foundation; LGA, large-for-gestational-age; NA, not applicable; NS, non-significant; T1D, type 1 diabetes; T2D, type 2 diabetes.
The first trials, from the early 2000s, used intermittent CGM. Some used “professional” CGM, in which patients were blinded to the CGM data (see the article on p. 8 of this compendium), and others followed an intermittent use schedule. As time progressed, the trials reflected evolving use of CGM to the current day. That is, earlier studies began to suggest that CGM could improve outcomes, but lack of access to real-time data limited benefit. More recent studies of real-time CGM, in which around-the-clock data are available, have shown more benefit in terms of reduction in both A1C and time spent in a hypoglycemic range.
A major impediment to interpreting CGM studies is that no uniform standard has been employed for teaching people with diabetes how to use continuous data, and no standard follow-up is provided to ensure that dose adjustments are made. In some trials, written instructions were provided to patients regarding insulin dose adjustments, but in many others, targeted education was not provided beyond how to use the device. Additionally, rapid advances in technology are not well represented in the literature, although data from newer systems, such as the Dexcom G5 Mobile (Dexcom, San Diego, CA) and the FreeStyle Libre (Abbott, Alameda, CA), are becoming available.
The opinions expressed are those of the authors and do not necessarily reflect those of Abbott Diabetes Care or the American Diabetes Association. The content was developed by the authors and does not represent the policy or position of the American Diabetes Association, any of its boards or committees, or any of its journals or their editors or editorial boards.
Article Information
Dualities of Interest
I.B.H. has served as a consultant to Abbott Diabetes Care, Adocia, Bigfoot, and Roche. His institution has received research grant support from Medtronic.
T.B. has served on advisory boards of Bayer Health Care, Boehringer Ingelheim, DreaMed Diabetes, Eli Lilly, Medtronic, Novo Nordisk, and Sanofi. His institution has received research grant support, with receipt of travel and accommodation expenses in some cases, from Abbott Diabetes Care, Diamyd, GluSense, Medtronic, Novo Nordisk, Sandoz, and Sanofi. He has received honoraria for participating on the speakers bureaus of Bayer Health Care, Eli Lilly, Medtronic, Novo Nordisk, Roche, and Sanofi. He owns stock in DreaMed Diabetes.
A.L.P. has served on advisory boards for Abbott Diabetes Care, Becton Dickinson, Bigfoot, Boehringer Ingelheim, Eli Lilly, Lexicon, Livongo, Medscape, Merck, Novo Nordisk, OptumHealth, Sanofi, and Science 37. She has received research grant support from Dexcom and Mannkind. She participates on a speakers bureau for Novo Nordisk.J.J.C. participates in speakers bureaus for Janssen, Merck, Novo Nordisk, and Sanofi.
G.A. has served as a consultant and on a steering committee for Dexcom and on an advisory board for Novo Nordisk, and her institution has received research grant support from AstraZeneca and Novo Nordisk.
R.M.B.’s institution has received payment for his services as a research investigator, consultant, or advisory board member for Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Bristol-Myers Squibb/AstraZeneca, Dexcom, Eli Lilly, Hygieia, Johnson & Johnson, Medtronic, Merck, Novo Nordisk, Roche, Sanofi, and Takeda. R.M.B. has inherited Merck stock, volunteers for the American Diabetes Association and JDRF, and receives funding from the National Institutes of Health for diabetes technology research.
Acknowledgments
Writing support services for this compendium were provided by Carol Verderese of The Diabetes Education Group in Lakeville, CT. Editorial and project management services were provided by Debbie Kendall of Kendall Editorial in Richmond, VA.
Author Contributions
All authors researched and wrote their respective section(s). Lead author I.B.H. reviewed all content and is the guarantor of this work.
REFERENCES
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