Nwanaji-Enwerem · Clinical epigenetics 2021 · post-hoc analysis of a randomized controlled trial · n=192

An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

Cited 19 times in the scientific literature.

Level 2 - randomized trial

Post-hoc analysis of a four-arm randomized controlled trial

PubMed 34920739 · doi:10.1186/s13148-021-01218-y · record verified 2026-08-29

What was done

Researchers conducted a post-hoc analysis of a randomized controlled trial involving 192 overweight or obese postmenopausal breast cancer survivors. Participants were allocated to one of four 6-month intervention arms: metformin alone, placebo alone, lifestyle weight loss with metformin, or lifestyle weight loss with placebo. The primary outcome was change in biological aging measured via epigenetic age biomarkers.

What was found

Epigenetic age correlated significantly with chronological age at baseline (r = 0.20 to 0.86, P < 0.005). However, after 6 months, no statistically significant associations or differences in epigenetic age acceleration/deceleration were observed between any of the intervention arms.

Why it matters

Despite preclinical and observational interest in metformin and caloric restriction as anti-aging therapies, a 6-month intervention was insufficient to alter established epigenetic clocks in this clinical population.

Limits

The study is a post-hoc analysis with a relatively short 6-month intervention window. Findings are limited to overweight and obese postmenopausal breast cancer survivors and may not generalize to broader or healthier populations. Specific clock metrics evaluated and exact effect sizes across individual clocks were not detailed in the abstract.

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