Monday, June 15, 2026

For adults with prediabetes, lifestyle intervention lowered risk of developing multiple chronic conditions

NIH-supported, long-term clinical trial found no difference between metformin and placebo.

A clinical trial supported by the National Institutes of Health (NIH) found that adults with prediabetes assigned to a lifestyle intervention had a significantly lower risk of developing multiple chronic health conditions (known as multimorbidity) over time than those assigned to a placebo. This study, which followed participants for over two decades, also found that participants assigned to receive metformin did not experience a statistically significant reduction in multimorbidity risk. The findings, published in JAMA, highlight the lasting benefits of lifestyle programs that may lower risk of the development of chronic conditions.

“Multimorbidity is a common issue, and few interventions have been found to prevent or delay developing multiple chronic conditions,” said Marcel Salive, M.D., first author of the study, from NIH’s National Institute on Aging (NIA). “Our work showing that healthy lifestyle intervention can significantly lower the burden of multimorbidity is a step forward in addressing this growing problem.”

Previous research has shown that both metformin and lifestyle interventions have been successful in preventing or delaying diabetes and metabolic syndrome, but the researchers in this study wanted to determine whether these interventions could prevent or delay multimorbidity in addition to diabetes. The clinical trial was conducted in 27 sites in the U.S. and followed 1,173 participants who were at high risk of diabetes, were enrolled in Medicare, and consented to the linkage of their Centers for Medicare & Medicaid (CMS) claims. In the first part of the study, the NIH Diabetes Prevention Program (DPP), from 1996 to 1999, participants were randomly assigned to an intensive lifestyle intervention, metformin (a drug commonly used in the management of Type 2 diabetes), or placebo. They were then enrolled in the DPP Outcomes Study (DPPOS) and followed through 2021.

In the first part of the study, lifestyle participants were offered 16 individual sessions of interventions followed by monthly sessions for approximately two years. The behavior change program targeted reduced calories and fat and at least 150 minutes of physical activity a week to achieve greater than or equal to 7% weight loss from baseline. After DPP trial completion, all participants were offered the intensive lifestyle curriculum in groups during a six-month bridge period. During the outcomes study portion, all participants were offered quarterly group lifestyle sessions, and the original lifestyle participants received booster sessions twice annually.

By the end of follow-up, the researchers found that 85% of the study participants experienced two or more chronic conditions, with 82%, 85%, and 87% experiencing multimorbidity among lifestyle, metformin, and placebo groups, respectively. Compared with the placebo group, participants in the lifestyle intervention had 21% lower risk for two chronic conditions and 25% lower risk for three chronic conditions. Participants assigned to metformin did not experience a statistically significant reduction in risk for multimorbidity. The study examined 15 chronic conditions commonly tracked in Medicare data, including hypertension, heart disease, stroke, arthritis, chronic kidney disease, COPD, cancer, depression, dementia, osteoporosis, and diabetes. These results persisted even when diabetes was taken out of the multimorbidity definition.

“These findings are highly encouraging, reinforcing that lifestyle programs focused on diet and exercise may persistently lower the risk of developing multiple chronic conditions, beyond diabetes,” said Griffin P. Rodgers, M.D., Director of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “Furthermore, because lifestyle modifications can be safe and cost-effective, sustaining these healthy behaviors among people at risk of diabetes may help reduce not only the individual health burden, but also broader healthcare spending.”

About the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): The NIDDK, a component of the National Institutes of Health (NIH), conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. https://www.niddk.nih.gov

About the National Institute on Aging (NIA): NIA seeks to understand the nature of aging and diseases associated with growing older, with the goal of extending the healthy, active years of life. www.nia.nih.gov

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference

Salive ME, et al. Lifestyle and metformin interventions and risk of multimorbidity in adults with prediabetes. JAMA. 2026. DOI: 10.1001/jama.2026.8492