🔬TODAY’S BREAKTHROUGH
A rigorously conducted randomised, double‑blind, placebo‑controlled trial tested metformin in older adults with probable sarcopenia and prefrailty or frailty. The drug did not improve the primary performance measure and was associated with more adverse events.
The Discovery:
In MET‑PREVENT, 72 participants aged 65 years and older were assigned to metformin 500 mg three times daily or placebo for 4 months. The primary outcome, 4‑meter walk speed at 4 months, was 0.57 m/s with metformin versus 0.58 m/s with placebo, an adjusted effect of 0.001 m/s with p=0.96. No key secondary outcomes improved, while adverse events were more frequent with metformin.
The Science:
Design and population: Double‑blind, randomised, parallel‑group trial at two NHS Trusts. Inclusion required 4‑m walk speed <0.8 m/s plus low handgrip or slow sit‑to‑stand, consistent with EWGSOP 2019 probable sarcopenia. Mean age 80.4 years.
Intervention: Metformin 500 mg orally three times daily versus matching placebo for 4 months; intention‑to‑treat analysis for efficacy, all‑treated for safety.
Primary outcome: Adjusted between‑group difference in 4‑m walk speed at 4 months. Result not significant and far below the 0.1 m/s minimal clinically important difference.
Secondary outcomes: No significant differences for grip strength, SPPB, 6‑minute walk distance, appendicular lean mass, or activities of daily living.
Safety: Adverse events occurred in 100 percent of metformin versus 92 percent of placebo participants. Serious adverse events in 26 percent versus 8 percent. Hospital admissions 12 versus 3. Total AEs 108 versus 77. One death occurred in the metformin group, judged unrelated.
Context: Prior trials show mixed effects in less‑impaired older adults; authors note this MET‑PREVENT cohort had greater frailty and slower baseline gait.
Your Action:
Do not assume metformin improves sarcopenia or frailty outcomes in very old, functionally impaired adults. Treatment choices should be made with a clinician who can weigh risks, benefits, and alternatives for your situation.
This trial does not support off‑label use of metformin for physical performance in this population.
Bottom Line:
In frail older adults with probable sarcopenia, metformin did not improve gait speed or other functional outcomes and produced more adverse events than placebo.
Source:
Metformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET‑PREVENT): a double‑blind, randomised, placebo‑controlled trial. The Lancet Healthy Longevity. Witham MD, McDonald C, Wilson N, et al. Published March 24, 2025.
https://doi.org/10.1016/j.lanhl.2025.100695
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.