Longevity
Metformin
Glucophage, dimethylbiguanide
Metformin is an oral biguanide and the first-line drug for type 2 diabetes worldwide. It is included here because it is widely used off-label as a longevity and metabolic-health compound, frequently alongside peptides.
Also known as: Glucophage, Glucophage XR, Fortamet, Riomet, dimethylbiguanide
- Status
- Metformin is approved by the U.S. FDA and has official prescribing information.
- Evidence
- Approved labeling. Official prescribing information exists, based on clinical trials in people.
- Half-life
- Approximately 5 hours for the immediate-release form.
- How it's taken
- Oral tablet, immediate or extended release
- Mechanism
- Metabolic (non-incretin)
- Pathways
- Insulin Signalling
How Metformin works
Metformin inhibits mitochondrial complex I, raising the cellular AMP to ATP ratio and activating AMP-activated protein kinase. The consequences are reduced hepatic gluconeogenesis, increased peripheral insulin sensitivity, and a shift toward catabolic metabolism. It also alters the gut microbiome and increases GLP-1 secretion, which appear to contribute meaningfully to its glycaemic effect.
What research has looked at
- Decades of clinical use, an extremely well-characterised safety profile, and low cost.
- The UKPDS trial reported a cardiovascular mortality benefit in overweight patients with type 2 diabetes, which is why it became first-line.
- It does not cause hypoglycaemia when used alone, because it does not stimulate insulin secretion.
- Observational data suggesting lower cancer and mortality rates in metformin users motivated the TAME trial, which is designed to test whether it affects ageing directly.
Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.
Reported side effects and risks
- The longevity claims remain unproven in humans. The observational data are subject to time-related biases, and the definitive trial has not reported.
- Evidence indicates metformin blunts the adaptations to aerobic exercise training, including mitochondrial and insulin-sensitivity improvements — a genuine tension for anyone taking it for healthspan while also training.
- Vitamin B12 deficiency develops with long-term use and should be monitored.
- Gastrointestinal intolerance — diarrhea, nausea, abdominal discomfort — is common and is the usual reason for discontinuation.
- Lactic acidosis is rare but serious, and it is contraindicated in significant renal impairment.
- It is a prescription medication.
Sources
- FDA approved-drug listing for metformin · U.S. Food & Drug Administration
- DailyMed prescribing information for metformin · NIH · DailyMed
- PubMed research on metformin AMPK exercise adaptation TAME longevity · NIH · National Library of Medicine
- DrugBank record for metformin · DrugBank
Track Metformin in Peptide Vault
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Related compounds
Metformin FAQ
What is Metformin?
Metformin is an oral biguanide and the first-line drug for type 2 diabetes worldwide. It is included here because it is widely used off-label as a longevity and metabolic-health compound, frequently alongside peptides.
How does Metformin work?
Metformin inhibits mitochondrial complex I, raising the cellular AMP to ATP ratio and activating AMP-activated protein kinase. The consequences are reduced hepatic gluconeogenesis, increased peripheral insulin sensitivity, and a shift toward catabolic metabolism. It also alters the gut microbiome and increases GLP-1 secretion, which appear to contribute meaningfully to its glycaemic effect.
Is Metformin FDA approved?
Yes. Metformin is approved by the U.S. FDA and has official prescribing information. Evidence level: approved labeling. Official prescribing information exists, based on clinical trials in people.
What is the half-life of Metformin?
Reported half-life: Approximately 5 hours for the immediate-release form.
How is Metformin taken?
Oral tablet, immediate or extended release.
What side effects have been reported with Metformin?
Reported in the sources: The longevity claims remain unproven in humans. The observational data are subject to time-related biases, and the definitive trial has not reported; Evidence indicates metformin blunts the adaptations to aerobic exercise training, including mitochondrial and insulin-sensitivity improvements — a genuine tension for anyone taking it for healthspan while also training; Vitamin B12 deficiency develops with long-term use and should be monitored; Gastrointestinal intolerance — diarrhea, nausea, abdominal discomfort — is common and is the usual reason for discontinuation; Lactic acidosis is rare but serious, and it is contraindicated in significant renal impairment; It is a prescription medication.
Educational summary compiled from the sources listed above. Not medical advice. Peptide Vault does not sell, source or recommend any compound. Talk to a qualified clinician before starting or changing anything.