Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 31557380 · doi:10.1111/acel.13039
What was done
In the multicenter MASTERS trial, healthy men and women aged 65 and older were randomized to receive 1,700 mg/day metformin (n = 46) or placebo (n = 48) alongside 14 weeks of supervised progressive resistance exercise training. Measured outcomes included lean body mass, thigh muscle mass, CT-derived thigh muscle area and density, muscle strength, and vastus lateralis biopsy analyses for fiber hypertrophy, satellite cells, macrophage abundance, fiber type percentages, and AMPK/mTORC1 signaling.
What was found
Placebo gained significantly more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT-assessed increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. Strength gains showed a non-significant trend for being blunted with metformin. Muscle biopsies showed no group differences in fiber hypertrophy, satellite cell, or macrophage abundance; however, placebo had a decreased type I fiber percentage while metformin did not (p = .007). Metformin increased AMPK signaling and showed a trend for blunted increases in mTORC1 signaling. Exact numerical changes and effect sizes were not reported in the abstract.
Why it matters
Metformin is widely studied for longevity, but these results show it directly inhibits skeletal muscle hypertrophy in response to resistance training in healthy older adults.
Limits
The abstract provides p-values but omits absolute numerical values and confidence intervals. The sample size was modest (94 participants), the duration was limited to 14 weeks, and the trial only evaluated healthy older adults, so findings may not generalize to individuals with diabetes or insulin resistance.