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Longevity Stack
Peptides/Metabolic

Retatrutide

Grade A

Phase II trial results showed ~24% mean weight loss at 48 weeks at the 12 mg dose — markedly exceeding semaglutide and tirzutide. Currently in Phase III; not yet FDA-approved but expected to be a landmark obesity and metabolic therapy.

Mechanism of Action

First-in-class triple agonist of GIP, GLP-1, and glucagon receptors. The GLP-1 and GIP arms drive glucose-dependent insulin secretion and satiety; the glucagon arm increases energy expenditure — producing the largest weight-loss effect of any incretin to date.

Typical Protocol

Dose
Titrated 2 mg → 4 mg → 8 mg → 12 mg
Frequency
Once weekly
Duration
Ongoing; weight regain occurs on cessation
Timing
Same day each week; any time of day
Route
Subcutaneous injection
Half-life
~6 days (supports once-weekly dosing)

Educational reference only — not medical advice.

Reported Benefits

  • ~24% mean weight loss at 48 weeks (Phase II)
  • Marked improvements in HbA1c, blood pressure, ApoB and liver fat
  • Convenient once-weekly dosing
  • Likely best-in-class cardiometabolic profile

Side Effects

  • Nausea, vomiting, diarrhea (especially during titration)
  • Injection site reactions
  • Reduced appetite to the point of inadequate protein intake — pair with resistance training and protein targeting
  • Theoretical pancreatitis and gallbladder risk (class effect)

Contraindications

  • Personal or family history of medullary thyroid carcinoma
  • Multiple Endocrine Neoplasia type 2
  • Pregnancy and lactation
  • Prior severe reaction to GLP-1 agonists

Known Interactions

Insulin and sulfonylureasRisk of hypoglycemia — dose reduction usually required.
Oral medicationsDelayed gastric emptying may alter absorption; separate timing for narrow-therapeutic-index drugs.

References

  1. [1]Triple-hormone-receptor agonist retatrutide for obesity — a Phase 2 trial — NEJM, 2023

Comparison vs Alternatives

All Peptides →
AttributeRetatrutideThis pageSemaglutideBPC-157
EvidenceGrade AGrade AGrade B
CategoryMetabolicMetabolicRegenerative
Best forTriple GIP/GLP-1/glucagon agonistGLP-1 receptor agonistTissue repair, gut integrity
Typical doseTitrated 2 mg → 4 mg → 8 mg → 12 mg0.25 → 2.4 mg250–500 mcg
FrequencyOnce weeklyWeekly1–2× daily
RouteSubcutaneous injectionSubcutaneous weekly (oral form available)Subcutaneous or oral (gut-localized)
Legal statusInvestigational; not yet FDA-approved. Currently available only via clinical trials.FDA-approved (Ozempic, Wegovy). Prescription required.Not approved by the FDA for human use. Sold as a research chemical in most jurisdictions.
ActionCurrent pageView →View →

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