Comparison
Metformin vs Rapamycin
Side-by-side of Metformin and Rapamycin. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Metformin
Metformin for longevity: biguanide mechanism of action, TAME trial status, anti-aging dosage, weight loss data, life extension evidence in non-diabetics.
Rapamycin
Rapamycin for longevity: sirolimus, an mTOR inhibitor with ITP mouse lifespan data. Off-label geroprotective dosing remains investigational.
Effects at a glance
Metformin
- •Reduces HbA1c by ~1.0 to 1.5 percentage points in type 2 diabetes; first-line agent in major guidelines
- •DPP trial: 31% reduction in T2DM incidence in adults with prediabetes over 2.8 years
- •Suppresses hepatic gluconeogenesis via AMPK activation and complex I inhibition
- •Long-term use depletes B12; annual monitoring recommended after year 2
- •Lifespan extension in non-diabetic humans is not established; TAME trial pending
- •MASTERS trial reported blunted resistance-training hypertrophy in older adults
Rapamycin
- •Inhibits mTORC1 signaling by binding FKBP12, reducing protein synthesis and relieving autophagy suppression
- •ITP mouse program reproduced lifespan extension of ~10 to 25% across multiple genetic backgrounds and sexes
- •Mannick trials showed improved influenza vaccine response in elderly adults using analogs of rapamycin
- •PEARL human trial reported acceptable safety at 5 to 10 mg weekly with some functional and lean-mass signals
- •Common dose-limiting adverse effects include stomatitis, acne-like rash, and mildly elevated lipid markers
- •CYP3A4 substrate: grapefruit, ketoconazole, and clarithromycin substantially raise rapamycin exposure
Side-by-side
| Attribute | Metformin | Rapamycin |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | Glucophage, Fortamet, Glumetza, dimethylbiguanide | Sirolimus, Rapamune |
| Half-life (hr) ↗ | 6 | 62 |
| Typical dose (mg) ↗ | 1500 | 6 |
| Dosing frequency | 1 to 3 times daily with meals; XR once daily | weekly (longevity protocols); daily for transplant indication |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 2.5 | 2 |
| Molecular weight | 129.16 | 914.17 |
| Molecular formula | C4H11N5 | C51H79NO13 |
| Mechanism | Suppresses hepatic gluconeogenesis primarily via AMPK activation and complex I inhibition; modestly improves peripheral insulin sensitivity and shifts gut microbiome composition. | Binds FKBP12, and the resulting complex inhibits mTORC1, reducing protein synthesis and autophagy suppression downstream of nutrient and growth-factor signaling. |
| Legal status | Prescription only (FDA approved for type 2 diabetes 1994) | Prescription only (off-label for longevity) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Category B; used in gestational diabetes and PCOS per current guidance | Not recommended |
| CAS | 657-24-9 | 53123-88-9 |
| PubChem CID | 4091 | 5284616 |
| Wikidata | Q19484 | Q410174 |
Safety profile
Metformin
Common side effects
- nausea
- diarrhea
- abdominal discomfort
- metallic taste
- decreased appetite
- B12 depletion (long-term)
Contraindications
- eGFR below 30 mL/min/1.73m2
- acute or chronic metabolic acidosis
- severe hepatic impairment
- acute heart failure
- iodinated contrast within 48 hours
Interactions
- iodinated contrast media: renal injury risk; hold 48 hours peri-imaging(major)
- alcohol (heavy use): elevated lactic acidosis risk(major)
- cimetidine: raises metformin plasma levels via OCT2 inhibition(moderate)
- insulin and sulfonylureas: additive hypoglycemia risk in combination(moderate)
- dolutegravir: raises metformin exposure via OCT2(moderate)
Rapamycin
Common side effects
- mouth ulcers (stomatitis)
- acne-like rash
- GI upset
- altered lipid panel
- delayed wound healing
Contraindications
- active infection
- severe hepatic impairment
- planned surgery (delayed wound healing)
- pregnancy
- live vaccines within dosing window
Interactions
- strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit): substantially raises rapamycin levels, toxicity risk(major)
- strong CYP3A4 inducers (rifampin, St John's wort): lowers rapamycin levels, reduced effect(major)
- ACE inhibitors: increased risk of angioedema(moderate)
- live vaccines: reduced vaccine efficacy due to immunosuppression(major)
Which Should You Take?
Metformin and Rapamycin score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is metabolic health and glucose control, pick Metformin.
- → If your priority is immune support, pick Rapamycin.
- → If your priority is healthspan extension, pick Metformin.
Edge case: Half-lives differ materially (Metformin ~6 hr vs Rapamycin ~62 hr). Rapamycin reaches steady state faster; Metformin is easier to dial in if tolerability is uncertain.
Default choice: either is defensible. Metformin edges out on goal breadth + legal accessibility; Rapamycin is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Metformin and Rapamycin?
Metformin and Rapamycin differ in category (pharmaceutical vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Metformin or Rapamycin?
Metformin half-life is 6 hours; Rapamycin half-life is 62 hours.
Can you stack Metformin with Rapamycin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper