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, and Anoop Misra randomized 127 North Indian adults aged 30 to 60 years with prediabetes to metformin 500 mg twice daily or placebo for 24 weeks. Both groups received lifestyle counseling. The trial was participant-blinded and outcome-assessor-blinded. Of 127 randomized participants, 112 completed the protocol. 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.