Comparison
Melatonin vs Metformin
Side-by-side of Melatonin 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.
Melatonin
Melatonin as a sleep supplement: 0.3-1 mg matches physiological output, 3-10 mg is pharmacological. Shifts circadian phase, shortens sleep latency.
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
Melatonin
- •Shortens sleep onset latency by ~7 to 12 minutes at physiological 0.3 to 1 mg doses
- •Advances circadian phase when taken 30 to 60 minutes before target bedtime, useful for jet lag and shift work
- •Does not meaningfully increase total sleep time in healthy adults without circadian misalignment
- •Endogenous nighttime production is not suppressed by short-term exogenous supplementation
- •Higher doses (3 to 10 mg) raise plasma levels above physiological range and often increase morning grogginess
- •Effective for delayed sleep-wake phase disorder and reducing jet-lag severity in eastward travel
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 | Melatonin | Metformin |
|---|---|---|
| Category | supplement | pharmaceutical |
| Also known as | N-acetyl-5-methoxytryptamine | Glucophage, Fortamet, Glumetza, dimethylbiguanide |
| Half-life (hr) ↗ | 0.75 | 6 |
| Typical dose (mg) ↗ | 0.5 | 1500 |
| Dosing frequency | daily, 30 to 60 minutes before target sleep time | 1 to 3 times daily with meals; XR once daily |
| Routes | oral, sublingual | oral |
| Onset (hr) | 0.5 | 1 |
| Peak (hr) | 1 | 2.5 |
| Molecular weight | 232.28 | 129.16 |
| Molecular formula | C13H16N2O2 | C4H11N5 |
| Mechanism | Agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, signaling biological night and promoting sleep-onset gating plus circadian phase shifts. | Suppresses hepatic gluconeogenesis primarily via AMPK activation and complex I inhibition; modestly improves peripheral insulin sensitivity and shifts gut microbiome composition. |
| Legal status | OTC in US; prescription in UK, EU, Japan | Prescription only (FDA approved for type 2 diabetes 1994) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement in US; Rx in UK, EU, Japan, Australia | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not routinely recommended | Category B; used in gestational diabetes and PCOS per current guidance |
| CAS | 73-31-4 | 657-24-9 |
| PubChem CID | 896 | 4091 |
| Wikidata | Q179243 | Q19484 |
Safety profile
Melatonin
Common side effects
- vivid dreams
- morning grogginess (higher doses)
- headache
- dizziness
Contraindications
- autoimmune disease (theoretical)
- concurrent anticoagulant therapy without monitoring
Interactions
- fluvoxamine: CYP1A2 inhibition raises melatonin levels substantially(major)
- warfarin: possible increased bleeding risk(moderate)
- benzodiazepines and alcohol: additive sedation(moderate)
- antihypertensives: may alter blood pressure response(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?
Melatonin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC, oral dosing, with a Tier-A outcome catalogued. Metformin is the right call when one of the conditionals below applies.
- → If your priority is sleep onset or sleep quality, pick Melatonin.
- → If your priority is circadian regulation, pick Melatonin.
- → If your priority is metabolic health and glucose control, pick Metformin.
- → If your priority is healthspan extension, pick Metformin.
Edge case: If you want to avoid prescription-only, Melatonin is the more accessible choice.
Default choice: Melatonin. Wider use case, a Tier-A evidence outcome catalogued, 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 Melatonin and Metformin?
Melatonin 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, Melatonin or Metformin?
Melatonin half-life is 0.75 hours; Metformin half-life is 6 hours.
Can you stack Melatonin with Metformin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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