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Metabolic

Retatrutide

Also known as Reta, LY3437943, LY-3437943, Triple G

Retatrutide (LY3437943) is an investigational once-weekly injectable triple agonist of the GIP, GLP-1, and glucagon receptors studied for obesity and metabolic disease, producing the largest weight reductions reported among incretin-class agents in Phase 2 trials.

Molecular weight4731.33 g/mol
Half-life~6 days (approximately 144-165 hours), supporting once-weekly dosing
CategoryMetabolic

Typical use cases

✓ Investigational treatment of obesity / weight reduction✓ Type 2 diabetes glycemic control (HbA1c reduction)✓ Metabolic dysfunction-associated steatotic liver disease (MASLD / liver fat reduction)✓ Improvement of cardiometabolic markers (blood pressure, triglycerides, waist circumference)✓ Increased energy expenditure via glucagon-receptor activation✓ Appetite and satiety modulation

Dosing guidelines

StartingTrials and community protocols commonly report a low starting dose of about 1-2 mg subcutaneously once weekly during the initial escalation phase.
MaintenanceMaintenance doses commonly reported in research/community protocols range from about 4-8 mg subcutaneously once weekly.
Max (studied)The highest dose studied in Phase 2 trials was 12 mg subcutaneously once weekly.

Titration

In published trials the dose was escalated gradually (e.g., starting around 1-2 mg weekly and stepping up roughly every 4 weeks toward target doses of 4, 8, or 12 mg), an approach commonly described as helping minimize gastrointestinal effects during escalation.

Reconstitution

Research-grade lyophilized powder is typically reconstituted with bacteriostatic water; the volume is chosen to give a convenient concentration for the intended dose. Swirl gently rather than shaking; do not use if cloudy or discolored.

Injection sites

Subcutaneous injection, typically rotated among the abdomen, thigh, and upper arm.

Storage & handling

Lyophilized powder is commonly stored refrigerated (2-8 C) and protected from light; after reconstitution it is kept refrigerated and used within a limited window. Avoid freezing reconstituted solution.

Side effects

  • Nausea Mild · Common
  • Vomiting Moderate · Common
  • Diarrhea Mild · Common
  • Constipation Mild · Common
  • Increased heart rate (dose-dependent) Moderate · Uncommon
  • Gallbladder events (e.g., cholecystitis) Severe · Rare

Research summary

Retatrutide is a 39-amino-acid lipidated synthetic peptide developed by Eli Lilly that simultaneously activates the GIP, GLP-1, and glucagon receptors, the latter adding an energy-expenditure component on top of the appetite and glycemic effects of dual incretin agonists. Human evidence comes primarily from a published Phase 2 program: a 48-week obesity trial (NEJM 2023, n=338) reported dose-dependent least-squares mean weight reductions up to about 24% at the 12 mg dose, a Phase 2 type 2 diabetes trial (Lancet 2023, n=281) showed HbA1c reductions of roughly 1.3-2.0 percentage points with weight loss up to ~17% at 12 mg, and a Phase 2a MASLD trial (Nature Medicine 2024, n=98) reported large reductions in liver fat (about 80% relative reduction at the 8-12 mg doses). Reported benefits also include improvements in blood pressure, triglycerides, and waist circumference. The dominant adverse events are gastrointestinal (nausea, vomiting, diarrhea, constipation), generally mild-to-moderate and concentrated during dose escalation, with dose-dependent heart-rate increases and isolated gallbladder events noted. Important limitations: retatrutide remains investigational and is not approved by any regulator, long-term cardiovascular outcome and safety data are not yet published, and the Phase 2 trials were of modest size and limited duration while the larger Phase 3 TRIUMPH program is still maturing. This entry is educational only and not medical advice.

Key references

  • https://en.wikipedia.org/wiki/Retatrutide
  • https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
  • https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01053-X/abstract
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC11271400/
  • https://pubchem.ncbi.nlm.nih.gov/compound/171390338
  • https://investor.lilly.com/news-releases/news-release-details/lillys-phase-2-retatrutide-results-published-new-england-journal

Related compounds

Tirzepatide → Semaglutide → Survodutide Mazdutide Cagrilintide

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Educational reference only — not medical advice. Dosing figures are commonly-cited ranges, not prescriptions. Consult a qualified clinician.

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