Can metformin (biguanide) be used for longevity and anti-cancer purposes?

Metformin for Longevity and Anti-Cancer Effects

Metformin is not currently recommended for longevity or anti-cancer purposes in non-diabetic individuals, as there is insufficient high-quality evidence supporting these off-label uses despite promising observational data. 1

Evidence for Anti-Cancer Effects

Colorectal Cancer Prevention

• Meta-analysis of 14 observational studies (n=459,607) showed that patients with type 2 diabetes using metformin had 27% reduction in colorectal cancer incidence compared to non-users (OR 0.73; 95% CI, 0.62-0.86) 1
• For patients with both colorectal cancer and diabetes, metformin was associated with improved cancer-specific survival (HR 0.69; 95% CI, 0.61-0.77) and overall survival (HR 0.75; 95% CI, 0.59-0.94) 1
• A 2016 Japanese trial (n=151) in non-diabetic patients with history of adenoma showed 40% reduction in adenoma recurrence with metformin (RR 0.60; 95% CI, 0.39-0.92) 1

Limitations of Cancer Prevention Evidence

• Most evidence comes from observational studies which are susceptible to confounding by diabetes severity and time-related biases 1
• Randomized controlled trials specifically designed to assess metformin's anti-cancer effects in non-diabetic populations are limited 2
• The American Gastroenterological Association only recommends considering metformin for chemoprevention against colorectal neoplasia in individuals with diabetes 1

Evidence for Longevity Effects

• While metformin has shown anti-aging effects in model organisms, evidence in humans remains limited 3, 4
• Metformin may provide indirect longevity benefits by reducing mortality associated with diabetes, cardiovascular disease, and cancer 4
• The mechanisms proposed include:
  • AMPK activation (enhancing cellular energy production) 5
  • Inhibition of mTOR (increasing autophagy) 5
  • Reduction of oxidative stress 4
  • Improved vascular function 4

Safety Considerations

Contraindications

• Metformin is contraindicated in patients with:
  • eGFR <30 mL/min/1.73 m² 6
  • Impaired hepatic function 6
  • Heart failure 6
  • Alcohol abuse 6
  • Acute illness with dehydration 6

Side Effects

• Common side effects include diarrhea, nausea, and vomiting 1, 6
• Long-term use may cause vitamin B12 deficiency requiring periodic monitoring 1
• Rare but serious risk of lactic acidosis, particularly in patients with renal insufficiency 6

Clinical Guidance

For patients interested in metformin for longevity or cancer prevention:

1. For diabetic patients:

   • Metformin is already first-line therapy and may provide additional benefits beyond glycemic control 1
   • Continue as long as tolerated and not contraindicated 1

2. For non-diabetic patients:

   • Current evidence does not support routine use for longevity or cancer prevention 1, 4
   • Consider only in high-risk populations under clinical supervision:
     • Those with prediabetes (especially BMI ≥35 kg/m², age <60 years, or women with prior gestational diabetes) 1
     • Patients with history of colorectal adenomas who also have diabetes 1

3. If prescribed off-label:

   • Start with low doses (e.g., 500 mg daily) and gradually titrate to minimize GI side effects 6
   • Monitor renal function every 3-6 months 6
   • Check vitamin B12 levels periodically, especially in those with anemia or peripheral neuropathy 1

Conclusion

While metformin shows promise for longevity and cancer prevention in preclinical and observational studies, current clinical guidelines do not support its use for these purposes in non-diabetic individuals outside of clinical trials. Patients seeking metformin for anti-aging or cancer prevention should be informed about the limited evidence and potential risks.