From the Guidelines
Metformin has been associated with slightly lower all-cause mortality and cardiovascular mortality compared to sulfonylureas, suggesting a potential positive effect on longevity. Metformin is primarily prescribed for type 2 diabetes at doses typically ranging from 500-2000mg daily [ 1 ]. Some longevity researchers take 500mg once or twice daily as an off-label use, though this practice remains experimental. If considering metformin for longevity, consultation with a healthcare provider is essential as it requires a prescription and has potential side effects including gastrointestinal issues, vitamin B12 deficiency, and rarely lactic acidosis [ 1 ]. The proposed anti-aging mechanisms include activation of AMPK (an energy-sensing enzyme), reduction of inflammation, improved insulin sensitivity, and mimicking some benefits of caloric restriction.
Key Considerations
- Metformin is contraindicated in patients with impaired kidney function, decreased tissue perfusion or hemodynamic instability, liver disease, alcohol abuse, heart failure, and any condition that might lead to lactic acidosis [ 1 ].
- Metformin may result in lower serum vitamin B12 concentration; therefore, periodic monitoring and supplementation is generally recommended if levels are deficient, particularly in those with anemia or neuropathy [ 1 ].
- Several ongoing clinical trials, including the TAME (Targeting Aging with Metformin) study, are investigating metformin's effects on longevity and age-related diseases.
- While animal studies have shown promising life-extension results, human evidence remains preliminary, making metformin an interesting but unproven intervention for extending healthy lifespan in humans without diabetes.
Important Factors
- The goal for HbA1c should be based on individualized assessment of risk for complications from diabetes, comorbidity, life expectancy, and patient preferences [ 1 ].
- Metformin is the drug of choice for patients with type 2 diabetes, in addition to lifestyle modification, due to its high efficacy, low cost, minimal hypoglycemia risk when used as monotherapy, and the potential for some weight loss [ 1 ].
From the Research
Effect of Metformin on Longevity
- Metformin has been reported to possibly prolong lifespan, besides improving glucose homeostasis, in some studies, but not all 2.
- A study found that metformin usage in advanced chronic kidney disease patients decreased the risk of all-cause mortality and incident end-stage renal disease 3.
- Metformin has been linked to many non-diabetes health benefits, including increasing healthy lifespan, but the mechanisms by which it exerts favorable effects on aging remain largely unknown 4.
- A comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls found that metformin patients had better survival than sulphonylurea patients, but metformin did not confer a benefit to longevity over matched controls when observed over a period of up to twenty years 5.
- Metformin use has been associated with a reduced risk of all-cause mortality, cardiovascular death, and cardiovascular events in patients with type 2 diabetes and chronic kidney disease 6.
Key Findings
- Metformin may have a beneficial effect on longevity in the short term, but this benefit may be outweighed by the effects of type 2 diabetes when patients are observed over a longer period 5.
- Metformin has been found to be safe and well-tolerated, and may be associated with cardioprotective and nephroprotective effects 2, 3, 6.
- Further research is needed to fully understand the effects of metformin on longevity and to determine whether it can be used as an anti-aging therapy 4, 5.