Director, Clinical and Translational Research Accelerator @Yale. Columnist @medscape.
How Medicine Works and When It Doesn't in bookstores now!
F. Perry Wilson, MD
Full piece on Medscape: buff.ly/F3z9Ev5
Still, it's hard to ignore. The habits you build seem to change your health for decades. A pill, even a good one, doesn't carry that kind of memory.
To be fair to metformin, it may not be inert. There's evidence it blunts some of the gains from exercise (VO2 max, for one). Its effect here might be good and bad cancelling out, rather than nothing at all.
Metformin is an old diabetes drug that's become the darling of the longevity crowd. Does it actually buy you healthier years? Two decades ago, a trial randomized people with prediabetes to metformin or lifestyle change. We finally know which group aged better. 🧵
And the gap widened the deeper they looked. At 3 or more conditions, lifestyle clearly pulled ahead. Overall that worked out to 10% fewer chronic conditions, and 43% lower risk of the costliest disease pairs. Metformin moved none of them.
The biggest surprise was diabetes itself. If metformin were going to win anywhere, surely it'd be here. Yet 60% of the lifestyle group developed type 2 diabetes over follow-up, vs 69% on placebo and 71% on metformin. The diabetes drug had the most diabetes.
The original DPP enrolled 3,234 adults with prediabetes and randomized them three ways: intensive lifestyle change (7% weight loss, 150 min/wk of activity), metformin at 850 mg twice daily, or a placebo pill.
You can't run a 40-year trial to test whether a daily pill keeps you healthy at 80. So they did the next best thing: took the Diabetes Prevention Program from the 1990s and linked its participants to their Medicare records 21 years later. buff.ly/roQTbQ4
The new question wasn't any single disease. It was multimorbidity (2 or more chronic conditions), the slow pileup that actually defines aging. They read it straight out of Medicare claims, decades after the trial ended.
First cut: almost everyone got there. 85% developed multimorbidity, and the raw rates barely differed by arm. But after adjustment, the lifestyle group had a real edge (HR 0.79). Metformin came out no different from placebo.
