Lifestyle Changes Outperform Metformin in Reducing Multimorbidity Risk Among Adults With Prediabetes: JAMA
USA: A long-term study published in the journal JAMA has found that intensive lifestyle intervention may help reduce the risk of developing multiple chronic diseases among adults with prediabetes, while metformin did not show a similar benefit over placebo.
The research was led by Marcel E. Salive from the Division of Geriatrics and Clinical Gerontology, National Institute on Aging, Bethesda, Maryland, and colleagues.
With aging populations and rising rates of chronic disease, preventing multimorbidity—the presence of two or more chronic conditions—has become a key public health goal. However, long-term evidence on interventions that can reduce the development of multiple chronic diseases remains limited.
To address this, researchers analyzed data from the Diabetes Prevention Program (DPP) and its long-term follow-up, the Diabetes Prevention Program Outcomes Study (DPPOS). The original trial enrolled adults at high risk of diabetes across 27 U.S. centers between 1996 and 1999 and randomly assigned them to intensive lifestyle intervention, metformin, or placebo.
The analysis included 1,173 participants with available Medicare data through 2021. Participants were followed for up to 21 years, with a median age of 74 years at follow-up; 68% were women. The primary outcome was multimorbidity, defined as the presence of at least two of 15 chronic conditions identified from Medicare records.
The study led to the following findings:
- Over the 21-year follow-up period, 85% of participants developed multimorbidity, defined as the presence of at least two chronic conditions, with a median of five conditions per participant.
- Multimorbidity occurred in 82% of participants in the lifestyle intervention group, 85% in the metformin group, and 87% in the placebo group.
- Participants assigned to the lifestyle intervention had a significantly lower risk of developing multimorbidity compared with those receiving placebo (HR, 0.79), representing a 21% risk reduction.
- No significant difference in multimorbidity risk was observed between the metformin and placebo groups (HR, 0.91).
- The protective effect of lifestyle intervention remained significant even after diabetes was excluded from the multimorbidity definition, indicating benefits beyond diabetes prevention.
- When the analysis was limited to combinations of the most costly chronic conditions, lifestyle intervention was associated with an even greater reduction in risk compared with placebo (HR, 0.57).
- Participants in the lifestyle group received ongoing support for weight loss and physical activity, including booster sessions and lifestyle education throughout the extended follow-up period.
The authors concluded that among adults with prediabetes, intensive lifestyle intervention was associated with a lower long-term burden of multimorbidity, whereas metformin was not. The findings highlight the potential of lifestyle-based prevention programs to reduce the accumulation of chronic diseases and support healthier aging over time.
Reference:
Salive ME, Tjaden AH, Ames JR, et al. Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes. JAMA. Published online June 15, 2026. doi:10.1001/jama.2026.8492
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