Can metformin (biguanide) be used to extend telomeres?

Metformin and Telomere Extension

Metformin has not been proven to extend telomeres in humans and should not be used for this purpose outside of clinical trials. While metformin shows some promise in aging research, current medical guidelines do not support its use specifically for telomere extension.

Current Evidence on Metformin and Aging

Established Uses of Metformin

Metformin is primarily indicated for:

• First-line therapy for type 2 diabetes 1
• Prevention of type 2 diabetes in high-risk individuals with prediabetes, particularly those with BMI ≥35 kg/m², age <60 years, or women with prior gestational diabetes 1

Emerging Research on Aging and Longevity

Recent research suggests potential anti-aging effects of metformin:

• A 2023 UK Biobank Mendelian randomization study found that metformin targets GPD1 and AMPKγ2 (PRKAG2) may promote healthy aging, with GPD1-induced HbA1c lowering associated with younger phenotypic age and longer leukocyte telomere length 2

• Animal studies have shown that metformin can extend lifespan in mice when administered at appropriate doses (0.1% w/w in diet), improving insulin sensitivity and reducing oxidative damage 3

• Metformin activates AMPK pathways which may induce autophagy and promote healthspan through hormesis-like mechanisms 4, 5

Limitations and Concerns

Lack of Clinical Evidence for Telomere Extension

• No major clinical guidelines recommend metformin for telomere extension 1
• The evidence for metformin directly extending telomeres in humans remains limited and controversial 5
• Current studies show mixed results, with some suggesting benefits primarily through indirect mechanisms rather than direct telomere effects 5

Safety Considerations

• Long-term metformin use is associated with vitamin B12 deficiency, requiring periodic monitoring 1
• Metformin is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) 1
• Gastrointestinal side effects are common, including bloating, abdominal discomfort, and diarrhea 1

Clinical Decision Algorithm

1. For patients with diabetes: Use metformin as first-line therapy per established guidelines 1

2. For patients with prediabetes: Consider metformin only for those at high risk (BMI ≥35 kg/m², age <60 years, or women with prior gestational diabetes) 1

3. For healthy individuals seeking telomere extension:

   • Do not prescribe metformin specifically for telomere extension
   • Recommend evidence-based lifestyle interventions instead:
     • Regular physical activity (150+ minutes/week)
     • Mediterranean or DASH eating pattern
     • Weight management (7% weight loss if overweight)
     • Smoking cessation

4. For patients interested in aging research:

   • Discuss ongoing clinical trials like TAME (Targeting Aging with Metformin)
   • Explain that current evidence is preliminary and insufficient to support off-label use

Conclusion

While metformin shows promise in aging research and may have beneficial effects on healthspan through metabolic improvements, reduction of oxidative stress, and possibly effects on telomere biology 2, the current medical evidence and guidelines do not support prescribing metformin specifically for telomere extension. Patients interested in this application should be encouraged to participate in clinical trials rather than using metformin off-label for this unproven indication.