Metabolic & Fat Loss FDA Phase 3

Retatrutide

Also known as: LY3437943

Molecular Identifiers

Molecular Formula

C221H342N46O68

CAS Number

2381089-83-2

PubChem CID

171390338

UNII

0OAB1IN08F

Molecular Weight

4731.33 Da

Overview

Triple agonist of GLP-1, GIP, and Glucagon receptors, with a molecular weight of approximately 4,731 Da. Represents the next generation of metabolic peptides, acting on three incretin pathways simultaneously for weight and metabolism control.

In phase 3 clinical trials for the treatment of obesity and type 2 diabetes. Triple GIP/GLP-1/Glucagon agonist developed by Eli Lilly with promising results of up to 24% weight loss in phase 2.

Clinical interest in retatrutide centers on obesity and type 2 diabetes control through a novel route: simultaneous agonism of the GLP-1, GIP, and glucagon receptors. To GLP-1 and GIP — responsible for satiety, glucose-dependent insulin secretion, and incretin potentiation — is added glucagon agonism, which increases energy expenditure, hepatic lipolysis, and thermogenesis. In phase 2, it showed up to 24% weight loss over 48 weeks, surpassing semaglutide and tirzepatide.

It is currently in phase 3 clinical trials run by Eli Lilly for obesity and type 2 diabetes. It does not yet have regulatory approval from any agency. In some countries it circulates via research channels and compounding pharmacies as experimental off-label use, in a weekly subcutaneous protocol with mandatory escalation every 4 weeks to contain gastrointestinal effects.

It represents the third generation of incretin mimetics — after single agonists (semaglutide) and dual GLP-1/GIP agonists (tirzepatide) — and phase 3 data will determine whether adding the glucagon arm translates into sustained clinical benefit without unacceptable cardiovascular or hepatic cost.

In direct comparison with its peers, it offers the largest magnitude of weight loss observed in phase 2 among modern incretin mimetics, surpassing tirzepatide (dual GLP-1/GIP) and semaglutide (pure GLP-1). However, it still lacks the regulatory approval and the long-term cardiovascular and renal evidence base that have already consolidated semaglutide and, to a lesser extent, tirzepatide in clinical practice.

Extended notation: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-(α-Me-Leu)-(α-Me-Leu)-Asp-Lys(γGlu-AEEA-AEEA-C20diacid)-Ala-Gln-Aib-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser

Modified peptide — triple agonist with non-natural amino acids (Aib) and conjugated fatty acid

Half-life

~6 days

Administration Route

Subcutaneous

Category

Metabolic & Fat Loss

Mechanism of Action

  • GLP-1 receptor agonism (satiety, glucose-dependent insulin secretion)
  • GIP receptor agonism (potentiation of the incretin effect)
  • Glucagon receptor agonism (hepatic lipolysis, thermogenesis, energy expenditure)
  • Delayed gastric emptying
  • Reduction of hepatic steatosis via glucagon receptor activation

Dosage Protocol

Data compiled from the literature. This does not constitute medical advice.

Parameter Value
Dose 0.5-12 mg per week (subcutaneous)
Frequency Once per week
Timing Same day and time each week
Duration 24-48 weeks (with gradual dose escalation)

Reported Side Effects

Adverse effects described in the literature. Severity and frequency vary between individuals.

  • Nausea
  • Diarrhea
  • Vomiting
  • Decreased appetite
  • Constipation
  • Injection site reactions

Product Properties

Purity >98%
Appearance White lyophilized powder
Solubility Soluble in water and bacteriostatic water
Source Solid-phase peptide synthesis (SPPS) or recombinant expression
Storage Lyophilized: -20°C for up to 2 years, 2-8°C for up to 6 months. Reconstituted: 2-8°C for up to 4 weeks. Protect from light and moisture. Avoid repeated freeze-thaw cycles.

Presentations & Preparation

Vials of Retatrutide found in the research market:

5 mg10 mg15 mg20 mg30 mg40 mg60 mg

Reconstitution

  • Diluent: Bacteriostatic water
  • Volume: According to vial concentration
  • Inject the diluent slowly against the vial wall
  • Gently swirl until completely dissolved — never shake
  • Mandatory gradual escalation every 4 weeks

Storage

  • Lyophilized: Refrigerated 2-8°C
  • Reconstituted: Refrigerated 2-8°C (up to 30 days)
  • Protect from direct light
  • Do not freeze after reconstitution
Reconstitution Calculator

Scientific Studies

Published studies on Retatrutide.

2023 · N Engl J Med

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial

Jastreboff AM, Kaplan LM, Frias JP, Wu Q, Du Y, Gurbuz S, et al.
2023 · Lancet

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, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, et al.

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