Lifestyle change, not metformin, linked to less chronic disease

Clinical takeaway: For patients with prediabetes, lifestyle intervention may lower the long-term load of chronic illness, not just diabetes risk. This makes it worth the upfront investment in counseling and support. Metformin's benefits appear more limited to improved glucose control.

Most older adults eventually accumulate several chronic conditions, a costly reality that's hard to treat and harder to reverse. Preventing that pileup has long been a goal with little proof that any intervention delivers. A 21-year follow-up of a landmark diabetes-prevention trial now offers rare long-term evidence, and it points to lifestyle change over medication.

Adults randomized to intensive lifestyle intervension had a 21% lower risk of developing two or more chronic conditions than the placebo group and a 25% lower risk of three or more. The effect was largest for the costliest disease combinations, where lifestyle was tied to a 43% lower risk. Metformin, by contrast, didn't differ from placebo on any of these measures.

The lifestyle advantage held even after diabetes was excluded from the multimorbidity definition, suggesting the effect extends beyond delaying diabetes itself. Still, diabetes loomed large: 60% of the lifestyle group developed it over follow-up. Those who did faced higher multimorbidity risk no matter which group they started in.

Researchers linked Medicare claims to participants of the Diabetes Prevention Program, a trial that randomized adults with prediabetes to lifestyle, metformin, or placebo in the late 1990s and followed them for 21 years. Multimorbidity was defined as two or more of 15 chronic conditions identified from claims.

The contrast between lifestyle and metformin is the striking part: the drug that prevents diabetes didn't blunt the wider accumulation of chronic disease, while behavior change did. Because the multimorbidity outcome came from observational follow-up rather than the trial's randomized endpoint, the findings show a durable association rather than proof of cause. Still, the 21-year span is among the longest evidence yet that lifestyle change leaves a lasting mark on healthy aging.

"Because lifestyle modification can be safe and cost-effective, sustaining those behaviors among Medicare beneficiaries at risk of diabetes may help to reduce health burden and health care spending," wrote the authors, led by Marcel Salive, MD, of the National Institute on Aging.

Source: Salive ME. JAMA. 2026 Jun 15. Lifestyle and metformin interventions and risk of multimorbidity in adults with prediabetes