# Metformin Slowed Frailty and Turned Back Epigenetic Clocks in Two-Year Trial

_Evidence Level: Moderate · Musi N et al., medRxiv : the preprint server for health sciences, DOI 10.64898/2026.07.27.26359055_

*A Randomized Clinical Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance.*

- **Evidence Level**: Moderate
- **Why this grade**: Two-year randomized placebo-controlled trial in 145 older adults with glucose intolerance, still a single modest-sized study not yet repeated.
- **Facts**: Design: Preprint
- **Publication Types**: Journal Article, Preprint
- **Journal**: medRxiv : the preprint server for health sciences
- **Sample Size**: 145 non-frail or pre-frail older adults (avg 72) with glucose intolerance
- **Authors**: Musi N, Wang CP, MacCarthy D, Feng Z, Holmes JT, Suda M, Pirtskhalava T, Aslamy A, Wanagat J, Brooke R, Tchkonia T, Kirkland JL, Horvath S, Espinoza SE
- **Graded and published**: 2026-07-28
- **Last edited**: 2026-09-17
- **Topics**: Metformin, Frailty, Epigenetic Age
- **DOI**: https://doi.org/10.64898/2026.07.27.26359055
- **Free full text**: https://pmc.ncbi.nlm.nih.gov/articles/PMC13484371/
- **Original Source**: https://pubmed.ncbi.nlm.nih.gov/42620010/
- **Registration**: ClinicalTrials.gov NCT02570672 (https://clinicaltrials.gov/study/NCT02570672)

## Summary

Older adults with prediabetes took metformin or a placebo for two years. Those on metformin accumulated fewer health deficits over time, and two DNA-based age clocks in their blood ticked slower. The picture was mixed though: on the classic frailty checklist, metformin looked worse in year one, but only because the drug caused weight loss. It was well tolerated overall.

## Practical Takeaway

This study suggests metformin's anti-aging effects depend heavily on how you measure frailty.

---

_Canonical: https://longevity-germany.com/en/research/metformin-slowed-frailty-and-turned-back-epigenetic-clocks-in-two-year-trial · Part of Longevity Cities · Updated 2026-09-17_