Metformin vs Rapamycin
FDA Approved vs FDA Approved
synergistic Metformin and rapamycin target complementary longevity pathways. Metformin activates AMPK while rapamycin directly inhibits mTOR. Preclinical studies in mice show the combination extends lifespan more than either compound alone. Some longevity-focused clinicians prescribe both concurrently, though human clinical trial data for the combination is limited.
Molecular Data
Metformin Rapamycin
Weight 129.16 Da 914.17 Da
Half-life ~5 hours ~62 hours
Type Biguanide (C4H11N5) Macrolide lactone (C51H79NO13)
Key Benefits
Metformin
01 Improved insulin sensitivity and glucose regulation
02 Activation of AMPK, the master metabolic energy sensor
03 Potential lifespan extension and delay of age-related diseases (under investigation in TAME trial)
04 Reduced hepatic glucose output (gluconeogenesis suppression)
05 Modest weight loss or weight neutrality compared to other diabetes medications
06 Anti-inflammatory effects through NF-kB pathway suppression
07 Potential anti-cancer properties via mTOR inhibition and AMPK activation
08 Improved lipid profile with modest reductions in LDL cholesterol and triglycerides
Rapamycin
01 Lifespan extension demonstrated in every model organism tested (yeast, worms, flies, mice)
02 Upregulation of autophagy and cellular quality control mechanisms
03 Reduction of senescent cell burden and associated inflammatory secretome
04 Improved immune function at low pulsed doses (paradoxical immune enhancement)
05 Reduced age-related inflammation (inflammaging) via mTORC1 inhibition
06 Enhanced mitochondrial function and biogenesis
07 Potential reduction in age-related cancer risk through growth pathway suppression
08 Improved vaccine response in elderly populations at low intermittent doses
Side Effects
Metformin
Gastrointestinal distress (nausea, diarrhea, bloating, abdominal cramping) - most frequent complaint, affects up to 25% of users
Metallic taste in mouth
Decreased appetite
Flatulence and abdominal distension
Loose stools, particularly when initiating therapy or increasing dose
Rapamycin
Mouth sores / aphthous ulcers (most common, usually dose-dependent and self-limiting)
Mild lipid changes (elevated LDL cholesterol and triglycerides)
Temporary glucose elevation or mildly impaired fasting glucose
Mild gastrointestinal discomfort (nausea, loose stools)
Skin changes (mild acne, slower wound healing at injection/cut sites)
Contraindications
Severe renal impairment (eGFR below 30 mL/min/1.73m2)
Acute or chronic metabolic acidosis, including diabetic ketoacidosis
Known hypersensitivity to metformin
Acute conditions with potential for tissue hypoxia (decompensated heart failure, respiratory failure, recent MI, sepsis)
Severe hepatic impairment
Excessive alcohol intake (increases risk of lactic acidosis)
Active serious infection or immunocompromised state
Hypersensitivity to rapamycin/sirolimus or any macrolide compound
Severe hepatic impairment (rapamycin is extensively hepatically metabolized)
Planned major surgery within 2-4 weeks (impaired wound healing)
Pregnancy or breastfeeding
Concurrent use of strong CYP3A4 inhibitors without dose adjustment (ketoconazole, itraconazole, clarithromycin, grapefruit juice)
Research Evidence
Metformin Rapamycin
Status FDA Approved FDA Approved
References 5 studies 5 studies
Latest 2023 March 2023
FDA Approved Yes Yes
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This comparison is for educational and research purposes only. Consult a healthcare professional before use.