Comparison
Fisetin vs Metformin
Side-by-side of Fisetin and Metformin. 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.
Fisetin
Fisetin is a flavonoid found in strawberries with senolytic activity in mouse models. Hickson 2019 confirmed senescent-cell clearance in human adipose tissue.
Metformin
Metformin for longevity: biguanide mechanism of action, TAME trial status, anti-aging dosage, weight loss data, life extension evidence in non-diabetics.
Effects at a glance
Fisetin
- •Flavonoid found in strawberries; most potent natural senolytic in screening assays (Yousefzadeh 2018)
- •Hickson 2019 confirmed reduced senescent-cell burden in human adipose tissue at 20 mg/kg pulsed for 2 days
- •Pulsed Mayo protocol (20 mg/kg/day x 2 days monthly) is the only dose with human biomarker evidence
- •Daily low-dose (100-500 mg) is mechanistically weaker but commonly used
- •Low oral bioavailability; with-fat dosing modestly improves absorption
- •Active cancer is a relative contraindication pending clearer polyphenol-treatment data
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
Side-by-side
| Attribute | Fisetin | Metformin |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | Glucophage, Fortamet, Glumetza, dimethylbiguanide |
| Half-life (hr) ↗ | 2 | 6 |
| Typical dose (mg) ↗ | 500 | 1500 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | 1 to 3 times daily with meals; XR once daily |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 2.5 |
| Molecular weight | 286.24 | 129.16 |
| Molecular formula | C15H10O6 | C4H11N5 |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | Suppresses hepatic gluconeogenesis primarily via AMPK activation and complex I inhibition; modestly improves peripheral insulin sensitivity and shifts gut microbiome composition. |
| Legal status | OTC dietary supplement | Prescription only (FDA approved for type 2 diabetes 1994) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data | Category B; used in gestational diabetes and PCOS per current guidance |
| CAS | 528-48-3 | 657-24-9 |
| PubChem CID | 5281614 | 4091 |
| Wikidata | Q230614 | Q19484 |
Safety profile
Fisetin
Common side effects
- mild GI upset
- headache (rare)
Contraindications
- active cancer (theoretical, polyphenol interactions)
- pregnancy and lactation (insufficient data)
- concurrent CYP3A4-sensitive medications
Interactions
- statins (CYP3A4 substrates): theoretical reduction in statin clearance at high fisetin doses(minor)
- warfarin: theoretical CYP-mediated interaction; monitor INR if combining(moderate)
- other senolytics (rapamycin, dasatinib + quercetin): additive senolytic effect; pairing is investigational(minor)
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)
Which Should You Take?
Fisetin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Metformin is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick Fisetin.
- → If your priority is metabolic health and glucose control, pick Metformin.
- → If your priority is healthspan extension, pick Fisetin.
Edge case: If you want to avoid prescription-only, Fisetin is the more accessible choice.
Default choice: Fisetin. Lower friction to source, and broader goal coverage. Reach for Metformin only if your priority sits squarely in the goals it owns 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 Fisetin and Metformin?
Fisetin and Metformin differ in category (supplement vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Metformin?
Fisetin half-life is 2 hours; Metformin half-life is 6 hours.
Can you stack Fisetin with Metformin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper