Timely News and Notes for Primary Care Providers from the American Diabetes Association

The number of adults living with diabetes globally is set to more than double by 2050, according to estimates from the Global Burden of Disease Diabetes Collaborators (The Lancet, doi.org/gsdsnf). Running at just over a half billion cases in 2021, rates are predicted to hit 1.3 billion by 2050, with all countries expected to see increases.

According to the estimates, the global total diabetes prevalence was 6.1% in 2021. However, that statistic masks huge variances between sexes; among age-groups, regions, and countries; and even within individual countries. Overall, there was an increase of ∼90% in global prevalence of diabetes between 1991 and 2021. However, a substantial number of regions, countries, and territories notched increases of >100% or even >200%. The authors calculate an increase of nearly 60% in prevalence by 2050, resulting in 1.3 billion people living with diabetes, with approximately half of this increase driven by obesity and the balance the result of demographic changes. These findings suggest that substantial investment in health care systems will be needed in the coming decades.

“The rapid rate at which diabetes is growing is not only alarming, but also challenging for every health system in the world, especially given how the disease also increases the risk for ischemic heart disease and stroke,” lead author Liane Ong said in a statement (bit.ly/3rRJKYB).

Of 16 risk factors the authors examined, high BMI accounted for just over half of disability and mortality attributable to diabetes. Dietary, environmental, and occupational risks, low physical activity levels, and tobacco/alcohol use made up the balance. Again, the balance of risks varied substantially among regions and countries.

“While the general public might believe that [type 2 diabetes] is simply associated with obesity, lack of exercise, and a poor diet, preventing and controlling diabetes is quite complex due to a number of factors,” Ong said. “That includes someone’s genetics, as well as logistical, social, and financial barriers within a country’s structural system, especially in low- and middle-income countries.”

Although the main drivers of diabetes are understood and well described, prevalence rates continue to increase everywhere. With diabetes already a major public health concern, the authors underline that solutions are urgently needed to limit population exposure to the risk factors for diabetes.

In a timely coincidence, The Lancet Diabetes & Endocrinology (bit.ly/3DB7CCr) and Diabetes Care (bit.ly/3YjiJJR) have published article collections focusing on the broad influence of social determinants of health in diabetes. Taken together, the two collections offer a deep dive into the topic, covering diverse aspects of the wider living environment, socioeconomic and political contexts, and structural racism, which all have an outsized influence on diabetes outcomes. Much of the focus is on the United States, and the general impression is that these issues are probably solvable through considerable policy changes and with enough political will. However, the collections outline many concerns, including serious and persistent structural issues related to inequitable diabetes care in many countries.

High costs of medical care are forcing some people with diabetes to turn to crowdfunding campaigns, according to Sloan et al. (Annals of Internal Medicine, doi.org/kmtk). Their analysis of 313 randomly selected GoFundMe campaigns from individuals with diabetes reveals a myriad of requests for help with both direct and indirect medical costs. Some examples are obvious, such as looking for help paying medical bills or dealing with lost wages due to illness, but others are more surprising and often sorry tales of people trying to manage their disease with limited resources. Thirty-five percent of requests from individuals with type 1 diabetes were for diabetes alert dogs, which cost about $15,000 and are not covered by insurance. The authors found a median fundraising goal of $10,000, but only 14% of campaigns reaching their goal. In the sample examined, the median amount raised was $2,600.

Levek et al. (Diabetes Care, doi.org/kmtr) present the case of a teenage girl with type 1 diabetes and obesity who used fake calibration data with her advanced hybrid closed-loop automated insulin delivery system to omit insulin for weight loss. The case charts the experience of the teenager from the age of 13 years through to her hospitalization 2 years later with impaired consciousness and mismatches between device-measured and emergency department glucose readings that suggested deliberate circumvention of devices’ intended functioning. The authors warn that insulin omission for weight loss is increasingly common in teenagers with type 1 diabetes. Caregivers need to know about the potential for patients to circumvent diabetes technology to manipulate insulin delivery.

A series of trials have reported recently on the repurposing of modern diabetes drugs to treat overweight and obesity, with some drugs yielding substantial weight losses. There is a clear debate on this topic: the drugs appear to give substantial weight reduction, but when they are stopped, the weight usually returns. There are also questions about how these treatments fit with more traditional views on dietary and lifestyle changes and wider recommendations on obesity prevention and treatment.

Frank B. Hu (The Lancet Diabetes & Endocrinology, doi.org/kmtt) argues that, despite these pharmacological developments, addressing issues around social determinants of health and facing the fact that these drugs are or will be unaffordable for many are also important. He proposes that the focus should remain on healthier lifestyles as key to obesity prevention and management.

Meanwhile, offering a slightly different take are Stoops and Dar (New England Journal of Medicine, doi.org/kmtv), who argue that the “calorie-incalorie-out” assumption is an oversimplification of the situation with obesity. They argue instead that consideration should be given to the use of the newer drugs alongside considerable increases in spending on lifestyle interventions, including addressing disparities in access to healthy food and lifestyles.

“We believe state Medicaid agencies should expand their coverage of obesity management and treatment approaches beyond bariatric surgery and brief patient education to include multimodal approaches involving comprehensive lifestyle intervention programs and . . . approved adjunct pharmacotherapies,” they write.

So, what of those diabetes/weight-reduction pharmacotherapies? There have been numerous announcements this year suggesting significant progress and (perhaps) some opportunism on the part of the companies involved. Many details of these studies were also presented at the American Diabetes Association’s 83rd Scientific Sessions in June 2023.

• Lilly, the company behind tirzepatide, announced the results of the SURMOUNT-2 pivotal study (bit.ly/3Zxwwx1), revealing weight loss of 13–16% over 72 weeks in patients with obesity/overweight and type 2 diabetes—a result the company says will allow them to now pursue U.S. Food and Drug Administration (FDA) approval for this specific weight loss indication (bit.ly/3QpzLDU). Combined with earlier results of the SURMOUNT-1 trial (weight loss in obesity without diabetes), the findings appear to have given the company a chance at an approval for a weight loss indication independent of diabetes status. The drug was previously approved for the treatment of type 2 diabetes alone.

• Trial results for another Lilly drug, retatrutide, were published recently (New England Journal of Medicine, doi.org/gsdst4). The triple-mechanism investigational drug reduced weight by 24.2% over 48 weeks.

• Trial results were also announced for the Lilly drug orforglipron, an oral glucagon-like peptide 1 (GLP-1) receptor agonist being developed for weight loss in people with obesity. According to the report (New England Journal of Medicine, doi.org/gsdmf9), use of the drug resulted in weight loss of just under 13% over 26 weeks and just under 15% after 36 weeks. In a further phase II study of orforglipron in people with type 2 diabetes (The Lancet, doi.org/kmtw), the drug yielded a 2.1% reduction in A1C over 26 weeks in addition to weight loss.

• An investigational glucagon/GLP-1 receptor agonist drug from Boehringer Ingelheim and Zealand Pharma that was previously called BI 456906 and is now renamed survodutide led to weight loss of 15–20% at 46 weeks in people with overweight or obesity but not type 2 diabetes, with indications that its effects might not have peaked at that point (bit.ly/43Vko9s). “By activating both the glucagon and GLP-1 receptors, survodutide may both inhibit appetite and improve energy expenditure, thereby helping to treat the disease of obesity,” said Carel le Roux, the trial’s principal investigator. “These encouraging data support the further study of survodutide in larger phase III trials.”

• In findings reported in The Lancet (doi.org/kmtx), researchers found that oral semaglutide 50 mg/day in adults with obesity but not type 2 diabetes resulted in weight reduction of 15.1% after 68 weeks. The effect size was considerably larger than that seen with placebo and sets the oral version on par with the injectable version, potentially widening the market considerably for Novo Nordisk’s blockbuster diabetes drug. The company reportedly aims to file for FDA approval for the weight loss indication later in 2023.

A survey of continuous glucose monitoring (CGM) users (Markov et al., Journal of Diabetes Science and Technology, doi.org/kmtp) suggests that >85% of users faced at least one device malfunction in the previous year, and just over 35% experienced four or more disruptions. Only 15% of respondents reported no disruption to their full CGM wear time. Insertion issues and sensor dislodgement were common issues, as were medical care–related disruptions (most notably in the setting of imaging studies).

With regard to adverse glycemic outcomes, 36.5% and 12.4% experienced four or more episodes of hyperglycemia and hypoglycemia, respectively, following device disruption. However, only two respondents required an emergency room visit, and there were no hospital admissions.

One striking finding of the survey related to the continuity of CGM. After device disruptions, nearly 20% of respondents reported being unable to use CGM for ≥7 days. Nearly half needed a replacement CGM at least once, and nearly 10% needed seven or more replacement devices.

“The lack of redundancy of CGM devices is a feature of current prescribing and supply limitations, and it leads to adverse hyperglycemic and hypoglycemic events,” the authors write. “Advocacy is needed to motivate device and insurance companies to provide more than the exact numbers of monthly devices to account for the realities of daily wear more appropriately.”

A brief report in Diabetes Care by Lehmann et al. (doi.org/kmtq) describes progress in the development of noninvasive detection of hypoglycemia via smartwatch data. Specifically, a pilot study that involved 22 individuals suggests that a machine learning approach applied to data streams from a smartwatch had adequate performance in detecting hypoglycemia noninvasively. In addition, the model’s associations were consistent with previously identified physiological changes associated with hypoglycemia.

The American Diabetes Association (ADA) offers a wealth of engaging professional education courses, as well as helpful resources for clinical practice. The following are some of the latest offerings.

• Diabetes Is Primary. As advances in diabetes treatment and technology evolve at a rapid pace, primary care providers must face the challenge of staying up to date on the latest practice guidelines. ADA’s free “Diabetes Is Primary” continuing education (CE) program provides an excellent foundation on the clinical management of diabetes (bit.ly/3qaFcMt).

• Eye Care Awareness. Annual eye exams reveal whether patients’ blood glucose levels are affecting their eye health. Information sharing between diabetes care and eye care professionals is essential to preserve vision in people with diabetes. Sign up for eye health education programs and find eye exam referral and visit summary form letters and other helpful tools on the Focus on Diabetes website (bit.ly/3rSOUDA).

• Kidney Health Patient Education. People with diabetes can learn about lowering their sodium and sugar intake and making healthy food choices by registering for a free Kidney Smart class from the ADA and DaVita Kidney Care (bit.ly/3q5spuR).

• Incretins and Weight Management. This free CE program enhances health care professionals’ knowledge of current treatment and prevention strategies for diabetes and obesity, including the role of incretin therapy (bit.ly/43YQQIg).

• Overcoming Therapeutic Inertia. Despite many rapid advancements in diabetes care, we still have not made a meaningful difference in improving glycemic control in people living with type 2 diabetes. Clinicians can access free tools to establish and carry out timely therapeutic plans for every patient (bit.ly/3YheRsE).

• Diabetes and Mental Health. Living with diabetes can be stressful and, at times, exhausting. Behavioral and mental health care are integral parts of diabetes management. The ADA offers resources, including a free CE program and toolkit (bit.ly/3OjETGZ).

• Diabetes Technology. Clinicians can discover ways to improve patient outcomes with diabetes technology through the free “Making Diabetes Technology Work” certification program. This CE series includes interactive modules covering insulin pumps, continuous glucose monitoring, insulin delivery systems, and more (bit.ly/47guHHU).

• Type 1 Diabetes Care. This self paced CE program offers the latest evidence based guidelines on treating type 1 diabetes in clinical practice (bit.ly/3DK2kEt).

The 83rd Scientific Sessions of the American Diabetes Association, held in San Diego, CA, in June 2023, touched all the bases of diabetes research, including notable advances in the areas of technology, social determinants of health, and drug development. Many key presentations were summarized online as the meeting unfolded (ADAMeetingNews.org).

One storyline that grabbed our attention during the conference was news of the investigational once-weekly insulin icodec. New results were presented from the ONWARDS research program suggesting that once-weekly insulin icodec may be superior in terms of glucose control compared to once-daily insulin degludec and insulin glargine in people with type 2 diabetes. Data from the Novo Nordisk–sponsored ONWARDS 1 and 3 trials point toward both noninferiority and superiority in A1C reduction. In the ONWARDS 1 trial comparing weekly insulin icodec to daily insulin glargine, patients also spent more time in the target glucose range.

The data from ONWARDS 1 were also published in the New England Journal of Medicine (doi.org/gsdn9f), and data from ONWARDS 3 were reported in JAMA (doi.org/gsdzcj). Full reports are available on the Medscape (wb.md/3Kol3cN) and MedPageToday (bit.ly/3OBMz98) websites. Novo Nordisk also announced (bit.ly/3Kpk3VM) that it has submitted a biologics license application to the U.S. Food and Drug Administration for once-weekly insulin icodec for use in patients with type 2 diabetes, with a decision expected in April 2024.

To learn more about ADA’s continuing education opportunities, including Diabetes Is Primary events in your community, please visit professional.diabetes.org/ce.