According to the CDC, 38.4 million Americans have diabetes. The largest group of, about a third of diabetes patients, are aged 65 or older. Yet clinical trials for treatments have focused primarily on younger patients who are less likely to have other complicating diseases. Guidelines for treating older patients have traditionally considered a timeline of several years for positive results. With new drugs, such as the popular GLP-1s, demonstrating efficacy much more quickly than insulin, how clinicians treat diabetes is changing.
On May 10, the Journal of the American Geriatric Society (JAGS) awarded its 2023 Editor’s Choice Award to“Glycemic control and diabetes complications across health status categories in older adults treated with insulin or insulin secretagogues: The Diabetes & Aging Study.” In this study, researchers from Yale School of Medicine, the University of Chicago, and Kaiser Permanente evaluated whether commonly recommended target HbA1c levels for older adults with type 2 diabetes correspond to better health. HbA1c, or glycated hemoglobin, is an indicator of elevated blood sugar, which can lead to vision loss, kidney failure, nerve damage, and cardiovascular disease. Using data on 63,400 adults aged 65 and over who have been treating type 2 diabetes with insulin or sulfonylureas, they observed that when older adults in good health with type 2 diabetes had HbA1c levels that were higher or lower than the recommended range, they experienced more risk for complications requiring emergency treatment, such as heart attacks and hypoglycemia. However, in older diabetic adults in poor health, who constituted about a quarter of the patients in the study, HbA1c levels that deviated from the recommended HbA1c range did not experience additional complications.
The study confirms longstanding recommendations for a lighter hand when medicating diabetic older adults in poor health, as drug side effects and the burden of medicating outweigh the benefits of strictly regulating blood sugar levels. An editorial published earlier in JAGS suggested an analogy with the TV gameshow “The Price Is Right”: “In some ways, diabetes management for older adults has become a ‘Price is Right’ for glycemic control, relaxing hemoglobin A1c (HbA1c) targets to avoid medication burden and hypoglycemia, but not too much as to exacerbate diabetic complications.”
However, guidelines for diabetes management in older adults may need even more refinement with the recent introduction of new non-insulin medications for diabetes, says Elbert Huang, MD, director of the UChicago Center for Chronic Disease Research and Policy and a coauthor on the JAGS paper. He also co-wrote a Clinical Insight published in JAMA Internal Medicine this April that offers suggestions for classifying and treating adults aged 65 and older with type 2 diabetes with three new types of drugs: glucagon-like peptide 1 receptor agonists (such as semiglutide), sodium glucose transporter 2 inhibitors (such as empagliflozin), and glucose-dependent insulinotropic polypeptide (such as tirzepatide).
Specific guidelines for treating older adults with diabetes are overdue, in part because early trials of diabetes medications excluded older patients, even though most people with diabetes are older adults.
“Historically what we've said is that the sickest patients should get less medication because they're likely to not benefit from intensive glucose control achieved with medications,” Huang said. “Basically, it goes back to insulin: the original trial comparing moderate and intensive glucose control in type 2 diabetes was conducted during a time when the number of available drug classes were limited to drugs like insulin and sulfonylurea. That trial showed that people do better with lower blood sugar, but you had to live for at least 10 years to see the benefit.”
Additional studies in type 1 diabetes demonstrated that early treatment of diabetes produces lasting benefits for two or three decades. “That led to the thinking that people with shorter life expectancies were not likely to benefit from treatment if they did not live long enough to experience the benefits. That became a big part of the ideas around how to individualize treatments for older people who had been left out of the original trial,” Huang said.
The exclusion of older adults from early trials stems in part from the complexity of aging, which can include multiple diseases and medical conditions occurring simultaneously. However, their absence meant the studies essentially did not represent how diabetes presents in the real world. “The majority of people with diabetes are over 65, so our evidence was not based in the majority of people with the disease,” says Huang.
Minimal treatment, or the same standards?
Interpretation of the resulting data has led to two major viewpoints on diabetes management: one recommending minimal treatment, given minimal evidence for health benefits in older adults, the other recommending that older adults be treated according to the same standards as younger people with diabetes.
While contemporary diabetes drug trials now also include older adults, adults with other medical conditions are often still excluded based on what Huang describes as “physiologic aging”: certain symptoms, history of disease, or coincidence of diseases such as cancer and heart disease can disqualify people from participating in the trials. Yet, he argues, patients with such conditions are representative of average geriatric diabetes patients, and physicians must be able to treat them.
The new drugs, which reduce food cravings and slow digestion, have fewer risks for weight gain and hypoglycemia than insulin. They also demonstrate health benefits such as reductions in cardiovascular events (not seen with insulin)—as soon as 3 to 18 months from beginning treatment—meaning that health improvements previously considered too risky or too far in the future for patients with limited life expectancy now need to be reevaluated.
Over a decade after Huang helped write the first care guidelines for diverse patient populations, which classified older patients into three groups with differing targets for HbA1c levels based on their health, he offers an updated, data-driven approach for classification that considers the benefits and adverse effects of the newest medications. Overall, the availability of new medications means that many older people will benefit from them but the need to individualize diabetes treatment plans based on health status, patient preferences, polypharmacy, and drug costs will endure.
“There needs to be more research to confirm these recommendations”–such as the 2023 JAGS study—"but while we're waiting for the new research, here are recommendations on how to act now,” he said.
“For many years people have talked quite vaguely about older patients, saying, ‘This older patient is complex,’ ‘This older patient is frail. Now we have tools that are much more specific and reproducible,” Huang said. “And now we can with greater specificity say who is missing from the trials, which could help us reexamine trial data and reshape how we design trials in the future.”
