Type 2 diabetes prevention strategies may not provide protection against cardiovascular diseases in adults
New findings from the Diabetes Prevention Program Outcomes Study (DPPOS) show that weight reduction through lifestyle changes or taking metformin, a medication that controls high blood glucose (sugar) levels to treat type 2 diabetes, may not provide additional protection against cardiovascular diseases in people with diabetes or at high risk of diabetes (prediabetes).
The Diabetes Prevention Program (DPP) was a landmark trial that transformed the way we approach type 2 diabetes prevention. Launched in 1996, the randomized controlled clinical trial recruited a diverse cohort of people at high risk for type 2 diabetes and demonstrated that the disease can be effectively prevented or delayed through lifestyle interventions (moderate physical activity aimed at reducing weight) or with metformin. Even though the trial was completed in 2001, the ongoing DPPOS continues to follow most DPP participants, and the data show that lifestyle changes or metformin treatment continues to provide long-term benefits in preventing or delaying type 2 diabetes even after two decades. Because people with type 2 diabetes are at increased risk for cardiovascular events such as heart attacks and strokes, the DPPOS researchers sought to determine whether lifestyle changes or metformin can also prevent or delay cardiovascular episodes. In this new analysis, they found that, surprisingly, neither lifestyle interventions nor metformin had a significant impact, either beneficial or unfavorable, on the incidence of cardiovascular events despite the improvement of cardiovascular risk factors in the lifestyle intervention group. One of the reasons behind this result could be that more time is needed for these interventions to show a beneficial effect on cardiovascular health. Other potential explanations include the DPPOS participants receiving a less intensive lifestyle intervention than in DPP, as well as their extensively using out-of-study medications, including those that lower blood lipid (fat) levels and blood pressure. These medications may have diluted the differences between study groups. This suggests that even though metformin and lifestyle intervention reduce the risk of type 2 diabetes, they may not be effective against cardiovascular disease when blood glucose, lipids, and blood pressure are well controlled.
Continuing to investigate the effects of metformin and lifestyle interventions on cardiovascular health will help optimize diabetes prevention and care and may provide important clues to cardiovascular disease prevention. Further research is needed to better understand and clarify the long-term effects of these interventions.
Goldberg RB, Orchard TJ, Crandall JP, …Temprosa M; on behalf of the Diabetes Prevention Program Research Group. Effects of long-term metformin and lifestyle interventions on cardiovascular events in the Diabetes Prevention Program and its outcome study. Circulation 145: 1632-1641, 2022.