Metformin Therapy Increases Leukocyte Telomere Length, Telomerase Activity, and Longevity Gene Expression in Asian Indians with Prediabetes: A 24-Week Participant-Blind, Outcome-Assessor-Blinded Randomized Controlled Trial.

Surya Prakash Bhatt, Shivam Pandey och Anoop Misra randomiserade 127 nordindiska vuxna i åldern 30 till 60 år med prediabetes till metformin 500 mg två gånger dagligen eller placebo i 24 veckor. Båda grupperna fick livsstilsrådgivning. Studien var deltagarblindad och utvärderarblindad. Av de 127 randomiserade deltagarna fullföljde 112 protokollet. Metformin increased leukocyte telomere length by 0.247 units versus 0.036 with placebo. Telomerase activity also rose, while placebo showed little change. SIRT1 expression increased. The mTOR result was described as context-dependent and needs mechanistic interpretation. The effects were reported as independent of sustained glycemic improvement. The trial supports a short-term effect on blood-cell aging markers in this specific prediabetes population. It does not show slower clinical aging, lower disease risk, improved function, or longer survival. The telomere result is a surrogate outcome, the intervention lasted only six months, and the sample was limited to Asian Indians with prediabetes. Larger, longer trials are needed before metformin can be treated as a longevity intervention.

Metformin over 24 weeks significantly elongated LTL, raised telomerase activity, and upregulated SIRT1, independent of glycemic control. While demonstrating metformin's geroprotective potential in healthy Asian Indians, the marked LTL response requires cautious interpretation, and validation in larger, long-term studies is needed.