Comparison
Low-Dose Naltrexone vs Metformin
Side-by-side of Low-Dose Naltrexone 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.
Low-Dose Naltrexone
Low dose naltrexone at 1.5 to 4.5 mg, one-tenth the 50 mg addiction dose. Compounded Rx. Small trials in fibromyalgia, Crohn's, Hashimoto's.
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
Low-Dose Naltrexone
- •Off-label use at 1.5 to 4.5 mg, roughly one-tenth the FDA-approved 50 mg addiction-treatment dose
- •Proposed mechanisms include brief opioid receptor blockade triggering rebound endogenous opioid release, plus TLR4 antagonism
- •Compounded prescription only; insurance rarely covers; cash prices 20 to 80 USD per month
- •Younger 2013 reported ~30% pain reduction in fibromyalgia at 4.5 mg in a small crossover trial
- •Smith 2011 reported endoscopic improvement in active Crohn's disease (n=40 placebo-controlled)
- •Vivid dreams affect 20 to 40% in first 2 weeks; manageable by switching to morning dosing
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 | Low-Dose Naltrexone | Metformin |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Glucophage, Fortamet, Glumetza, dimethylbiguanide |
| Half-life (hr) ↗ | 4 | 6 |
| Typical dose (mg) ↗ | 4.5 | 1500 |
| Dosing frequency | once daily, typically at bedtime | 1 to 3 times daily with meals; XR once daily |
| Routes | oral | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1.5 | 2.5 |
| Molecular weight | 341.4 | 129.16 |
| Molecular formula | C20H23NO4 | C4H11N5 |
| Mechanism | Brief mu-opioid receptor antagonism proposed to trigger compensatory upregulation of endogenous opioids; secondary TLR4 antagonism on microglia and immune cells contributes to anti-inflammatory effect. | Suppresses hepatic gluconeogenesis primarily via AMPK activation and complex I inhibition; modestly improves peripheral insulin sensitivity and shifts gut microbiome composition. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Prescription only (FDA approved for type 2 diabetes 1994) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not routinely recommended | Category B; used in gestational diabetes and PCOS per current guidance |
| CAS | 16590-41-3 | 657-24-9 |
| PubChem CID | 5360515 | 4091 |
| Wikidata | Q426444 | Q19484 |
Safety profile
Low-Dose Naltrexone
Common side effects
- vivid dreams
- sleep disruption
- headache
- mild GI upset
- fatigue (early)
Contraindications
- concurrent opioid use
- acute hepatitis or liver failure
- opioid dependence
- pregnancy (insufficient data)
Interactions
- opioid analgesics (oxycodone, morphine, codeine): blocks analgesic effect; precipitates withdrawal in dependent users(major)
- tramadol: blocks opioid component of analgesia(major)
- thyroid hormone replacement: may alter dose requirements after immune modulation; monitor TSH(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?
Low-Dose Naltrexone and Metformin 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 immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
- → If your priority is metabolic health and glucose control, pick Metformin.
- → If your priority is healthspan extension, pick Metformin.
Default choice: either is defensible. Low-Dose Naltrexone edges out on goal breadth + legal accessibility; Metformin 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 Low-Dose Naltrexone and Metformin?
Low-Dose Naltrexone and Metformin 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, Low-Dose Naltrexone or Metformin?
Low-Dose Naltrexone half-life is 4 hours; Metformin half-life is 6 hours.
Can you stack Low-Dose Naltrexone 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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