Lifestyle changes, but not metformin, were linked to a lower burden of chronic disease over time in adults with prediabetes. Digest
Lifestyle changes and metformin can delay or even prevent type 2 diabetes in people with prediabetes, but it remains unclear whether they also reduce the long-term risk of developing other chronic diseases. Researchers tested this possibility by tracking the long-term health of people who had participated in an earlier clinical trial.
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The original trial randomly assigned 3,234 adults with prediabetes to intensive lifestyle support, metformin, or placebo. During the roughly three-year trial, the lifestyle program aimed for at least 7% weight loss through lower calorie and fat intake and at least 150 minutes of physical activity per week, while metformin was prescribed at 850 mg twice daily as tolerated. After the trial ended, all participants were offered the lifestyle program in group classes over six months. They were then invited to join a follow-up study, which continued tracking their health. During this follow-up, all participants were offered one lifestyle session every three months, while those originally assigned to the lifestyle group were offered two additional sessions each year. These follow-up lifestyle sessions continued for about 12 years. Participants originally assigned to metformin typically had about 18 years of recorded metformin use, although the duration varied widely. The current analysis examined Medicare records from 1,173 participants over roughly 21 years from the start of the original trial, with about 10 years of records available per person. Researchers used the records to determine whether participants developed at least two of 15 chronic conditions and how many conditions they developed overall.
- Lifestyle support was linked to a slower accumulation of chronic conditions. Compared with the placebo group, the rate of developing at least two chronic conditions was 21% lower, and 25% lower for at least three conditions.
- The lifestyle group also developed fewer conditions overall. Participants in this group had about 10% fewer chronic conditions on average than those in the placebo group.
- Costly combinations of chronic conditions were less common with lifestyle support. Compared with placebo, the rate of developing a condition pair associated with especially high Medicare spending was about 43% lower.
- The lifestyle findings extended beyond diabetes prevention. The association remained when diabetes was left out of the condition count, suggesting that delayed diabetes alone did not explain the pattern. However, participants who developed diabetes were still more likely to accumulate other chronic conditions later.
- Metformin did not show the same broad benefit. Compared with placebo, it was not clearly linked to a lower rate of developing two or three chronic conditions, fewer conditions overall, or fewer condition pairs associated with especially high Medicare spending. One exception was a lower risk of developing three conditions when diabetes was excluded.
Many chronic diseases share underlying drivers, including excess body fat, poor metabolic control, and declining physical function. Unlike metformin, the lifestyle program addressed all three. Improvements across these areas could benefit several organ systems at the same time, reducing the likelihood that multiple conditions develop in the same person. Taking medications can also improve metabolic control and delay diabetes, but metformin may not produce the same coordinated changes. The observation that the lifestyle association remained after diabetes was removed supports this interpretation: delayed diabetes was likely one contributor, but not the full explanation.
A key limitation is that the analysis included only participants who were still alive, enrolled in Medicare, and willing to share their records, limiting how broadly the findings apply. Still, the findings underscore the limits of pharmaceutical treatment alone and the importance of lifestyle changes for long-term health. In episode #96, I explain how high-intensity interval training (HIIT), circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.