Retatrutide

Effects for which retatrutide has been studied. None of the following constitute an approved use.

• Body-weight reduction in adults with obesity (2023 Phase 2 published; Phase 3 ongoing)
• HbA1c reduction in adults with type 2 diabetes (2023 Phase 2 published; Phase 3 ongoing)
• Reductions in waist circumference and estimated visceral fat in the 2023 Phase 2 secondary endpoints
• Signal of improvements in liver-associated markers in participants with steatotic liver disease — exploratory

• First-in-class triple GIP / GLP-1 / glucagon receptor agonist
• Investigational; no marketing authorisation in any jurisdiction
• Weight-loss signal in the 2023 Phase 2 obesity trial at 48 weeks in the mid-twenties percentage range at the highest studied dose
• Glucagon-receptor activity distinguishes it from tirzepatide and semaglutide and contributes to its energy-expenditure profile in preclinical models

• 2023 Phase 2 obesity trial

  Adults with obesity, no diabetes. Mean body-weight reduction ~24% at 48 weeks at the 12 mg weekly dose vs. ~2% with placebo (Jastreboff et al., NEJM 2023).

• 2023 Phase 2 type 2 diabetes trial

  Adults with type 2 diabetes. Dose-dependent HbA1c and body-weight reductions across 36 weeks; magnitude at higher doses comparable to or larger than published tirzepatide Phase 3 results (Rosenstock et al., Lancet 2023).

Reported in the two published 2023 Phase 2 trials in obesity and in type 2 diabetes. Frequency was dose-dependent; higher doses produced more gastrointestinal effects.

• Nausea — Most common; typically transient; peak during titration
• Vomiting
• Diarrhoea
• Constipation
• Reduced appetite
• Injection-site reactions — Mild, localised
• Transient increase in heart rate — Dose-related; reported in the 2023 Phase 2 trials — typically small in absolute magnitude but consistent
• Changes in liver-associated markers — Small and reversible changes reported in some participants; not consistently signal-positive

Retatrutide is investigational. It is NOT FDA-approved, has NO approved indication, NO approved commercial formulation, and NO standardized public reconstitution instructions. Authentic trial drug is administered only under clinical-trial controls. Products sold online under the retatrutide name are unapproved third-party material — their identity, purity, mass, sterility, and formulation are not verified and may not match trial material. Use outside a controlled clinical trial is not supported by regulatory review. The items below are precautionary — they reflect what would ordinarily be flagged for compounds in this class and for an investigational agent with limited long-term human data.

• Investigational — no regulatory clearance in any jurisdiction
• No FDA-approved indication
• No approved commercial formulation
• No standardized public reconstitution instructions
• Authentic trial drug is administered only under clinical-trial controls
• Personal or family history of medullary thyroid carcinoma or MEN 2 — precautionary, given class-wide labelling of related incretin drugs
• History of pancreatitis — precautionary, given class-wide signals
• Pregnancy — no human safety data; effective contraception recommended if the compound is being studied in individuals of reproductive potential
• Breastfeeding — no human data
• Severe pre-existing gastrointestinal disease, including gastroparesis — precautionary, given the class effect on gastric emptying

Monitoring

• Body weight and body composition
• HbA1c and fasting glucose (where relevant)
• Heart rate (given the transient increase reported in the 2023 Phase 2 trials)
• Liver-associated markers
• Renal function during acute illness or dehydration
• Signs and symptoms of pancreatitis (severe abdominal pain radiating to the back)

• Is retatrutide available by prescription anywhere?

  No. Retatrutide is investigational and has not been approved by any regulator. It is not available on a legitimate prescription anywhere in the world. Any product marketed under the retatrutide name outside a clinical trial is unregulated and its identity, purity, and dose cannot be verified.

• How does retatrutide differ mechanistically from tirzepatide?

  Both compounds activate GIP and GLP-1 receptors. Retatrutide additionally activates the glucagon receptor, which in preclinical work contributes to increased energy expenditure and hepatic lipid handling. The clinical consequence of that third receptor is one of the questions Eli Lilly's TRIUMPH Phase 3 clinical development program is designed to answer.

• How much weight loss was seen in Phase 2?

  In the 2023 Phase 2 obesity trial (Jastreboff et al., NEJM 2023) at 48 weeks, mean body-weight reduction was in the mid-twenties percentage range at the highest studied dose (12 mg weekly), vs. ~2% with placebo. Individual outcomes vary substantially. Phase 3 will refine those numbers in larger, more diverse populations.

• What are the most common side effects?

  Dose-dependent gastrointestinal effects — nausea, vomiting, diarrhoea — as with every incretin-based drug in this class. Titration reduces intensity. A small dose-related transient increase in heart rate was also reported in the 2023 Phase 2 trials.

1. [1]

   Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial — Jastreboff AM, Kaplan LM, Frías JP, et al., New England Journal of Medicine (2023)

   https://doi.org/10.1056/NEJMoa2301972

2. [2]

   Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial — Rosenstock J, Frías JP, Jastreboff AM, et al., The Lancet (2023)

   https://doi.org/10.1016/S0140-6736(23)01053-X

3. [3]

   Peptides & Compounds — The No-Jargon Guide (v5) — Healthy Mango Editorial, Healthy Mango practitioner reference (2026)