Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.
Level 2 - randomized trial
Double-blind randomized controlled trial
PubMed 30548390 · doi:10.1111/acel.12880
What was done
Older adults (mean age 62 ± 1 years) completed 12 weeks of aerobic exercise training (AET) and were randomized in a double-blind fashion to either placebo (n = 26) or metformin (n = 27). The trial measured adaptations including fat mass, HbA1c, fasting plasma insulin, 24-hour mean glucose, glycemic variability, VO2 max, whole-body insulin sensitivity, skeletal muscle mitochondrial respiration, and mitochondrial protein synthesis rates.
What was found
Across both groups, AET reduced fat mass, HbA1c, fasting plasma insulin, 24-hour ambulant mean glucose, and glycemic variability (exact numerical changes not reported in the abstract). Metformin attenuated the AET-induced increases in whole-body insulin sensitivity and VO2 max. In the metformin group, there was no overall change in insulin sensitivity due to mixed positive and negative responders. Metformin also abrogated the exercise-mediated increase in skeletal muscle mitochondrial respiration, which correlated with changes in whole-body insulin sensitivity. Mitochondrial protein synthesis rates during training did not differ between groups.
Why it matters
These findings indicate that metformin co-administration can blunt key cardiorespiratory, metabolic, and mitochondrial adaptations to aerobic exercise in older adults.
Limits
The sample size was small (n = 53 total). The abstract does not report specific numeric values, effect sizes, or p-values for the outcomes. The study was limited to older adults undergoing 12 weeks of aerobic training and did not evaluate resistance exercise or alternative dosing schedules.