Retatrutide

Compound Details

Published Research

Peer-reviewed studies from PubMed.

• Retatrutide for Obesity and Knee Osteoarthritis — TRIUMPH-4 Phase 3 Trial

  2025Phase 3

  First Phase 3 result for retatrutide: TRIUMPH-4 demonstrated 28.7% mean body weight loss at the 12 mg dose over 68 weeks in adults with obesity and knee osteoarthritis, along with a 75.8% reduction in WOMAC pain scores — the largest weight loss reported for any anti-obesity agent in a Phase 3 trial.

  • 28.7% mean body weight loss (71.2 lbs) at 12 mg over 68 weeks
  • 75.8% reduction in WOMAC knee pain scores; 12% of patients pain-free
  • 58.6% of 12 mg group achieved ≥25% weight loss; 39.4% achieved ≥30%
  • 14.0 mmHg systolic blood pressure reduction at highest dose
• Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

  2023Obesity

  Phase 2 trial: retatrutide (GIP/GLP-1/glucagon triple agonist) once weekly for 48 weeks produced the largest weight reductions seen in any anti-obesity medication trial — up to 24.2% at the 12 mg dose.

  • 24.2% mean body weight reduction at 12 mg dose over 48 weeks
  • Dose-dependent weight loss across all treatment arms
  • 100% of participants on 12 mg achieved ≥5% weight loss
• Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes

  2023Metabolic

  Phase 2 trial in adults with type 2 diabetes: retatrutide showed clinically meaningful HbA1c improvements and robust, dose-dependent bodyweight reductions with a safety profile consistent with incretin-based therapies.

  • HbA1c reductions up to −2.02% at the highest dose
  • Bodyweight reductions up to 16.94% in participants with T2D
  • Glucagon receptor component adds energy expenditure not seen in dual agonists
• Glucagon receptor agonism enhances the metabolic benefits of GLP-1 receptor agonism

  2021Mechanism

  Preclinical evidence that adding glucagon receptor agonism to GLP-1 agonism increases energy expenditure, hepatic lipid oxidation, and weight loss beyond incretin effects alone — the mechanistic basis for triple agonists.

  • Glucagon receptor activation increases hepatic fatty acid oxidation
  • Combined GLP-1 + glucagon agonism increases energy expenditure 15–20%
  • Glucagon-driven thermogenesis enhances weight loss beyond appetite suppression alone
• Beyond dual satisf: the emerging landscape of triple hormone receptor agonists for metabolic diseases

  2023Review

  Review of the triple agonist landscape: rationale for combining GIP, GLP-1, and glucagon receptor activation, comparative analysis with dual agonists, and future directions for metabolic disease research.

  • Triple agonism addresses limitations of dual-agonist approaches
  • Glucagon receptor component specifically targets hepatic steatosis
  • Phase 2 data suggest potential best-in-class weight loss efficacy