Abstract
Introduction
Metformin has pleiotropic biological effects which might improve muscle function in older people. The MET-PREVENT trial tested the efficacy and safety of metformin as a therapy for sarcopenia and frailty in older people.
Methods
Double blind, randomised, parallel-group, placebo-controlled trial. Participants aged ≥65 with walk speed <.8m />s and low muscle strength (handgrip <16kg for women, <27kg for men, or 5x sit to stand >15s) were recruited from primary care and hospital clinics. Participants were randomised 1:1 using a web-based interactive system to receive 4 months of 500mg metformin or matching placebo 3x/day. The primary outcome, analysed by intention to treat, was the between-group difference in 4m walk speed at 4 months, adjusted for baseline values. Secondary outcomes included grip strength, short physical performance battery, six-minute walk distance, muscle mass by bioimpedance, quality of life and activities of daily living. All adverse events were recorded.
Results
Seventy-two participants were randomised, mean age 80 (SD 6) years. 42 (58%) were women, 42 (58%) were frail (Fried score ≥3); mean baseline 4m walk speed was 0.59 m/s (SD 0.22). 70 (97%) completed the trial (metformin 34/36, placebo 36/36). 14 (40%) discontinued metformin and 5 (14%) discontinued placebo. There was no difference in the primary outcome between the metformin (0.57 m/s [SD 0.19] m/s) and placebo group (0.58 m/s [SD 0.24]); adjusted treatment effect was 0.001 m/s (95%CI -0.06, 0.06); p=0.96. There was no significant effect on measures of muscle mass, physical performance, quality of life or activities of daily living. The metformin group had more adverse events (110 vs 77) and more hospital admissions (12 vs 3)
Conclusions
MET-PREVENT achieved successful recruitment with high retention rates, however metformin did not improve physical performance and was poorly tolerated with high rates of adverse events in older people with sarcopenia.