Reta

Reta/Retatrutide (LY3437943) is a first-in-class, single-molecule, triple hormone receptor agonist developed by Eli Lilly. It is a 39-amino acid synthetic peptide engineered to simultaneously activate the glucose-dependent insulinotropic polypeptide receptor (GIPR), the glucagon-like peptide-1 receptor (GLP-1R), and the glucagon receptor (GCGR). This triple-agonist design represents a novel therapeutic approach that builds upon the dual-agonist platform of tirzepatide (GIP/GLP-1) by incorporating glucagon receptor activation to enhance energy expenditure. The compound is currently in Phase 3 clinical trials for obesity, type 2 diabetes, and related comorbidities, with a New Drug Application (NDA) submission expected in late 2026 or early 2027.

Retatrutide exerts its effects through simultaneous activation of three key metabolic hormone receptors. GIPR agonism enhances glucose-dependent insulin secretion from pancreatic beta cells. GLP-1R agonism improves glycemic control by enhancing insulin secretion, suppressing glucagon secretion, slowing gastric emptying, and promoting satiety. GCGR agonism increases energy expenditure, contributing to greater body weight losses compared to GLP-1-based therapies.

• Obesity and Weight Management: Investigated for significant and sustained weight reduction. In a Phase 2 obesity trial, retatrutide demonstrated an average weight loss of 24.2% at 48 weeks in the 12 mg dose group. Phase 3 TRIUMPH-1 results have shown unprecedented weight loss approaching levels comparable to bariatric surgery.
• Type 2 Diabetes Mellitus: Studied for glycemic control with substantial improvements in HbA1c. In Phase 2 trials, retatrutide achieved an HbA1c reduction of 2.2%, with 82% of participants reaching glycemic targets. Phase 3 TRANSCEND-T2D-1 results were announced in 2026.
• Cardiometabolic Diseases: Investigated for cardiovascular and renal outcomes, metabolic dysfunction-associated steatotic liver disease (MASLD), and non-alcoholic fatty liver disease.
• Emerging Applications: Studied for knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea (OSA), and chronic low back pain.

CAS Number: 2381089-83-2
PubChem SID: 497620843
Molecular Formula: C₂₂₁H₃₄₂N₄₆O₆₈
Molecular Weight: 4,731.34 g/mol
Purity: ≥ 98% (batch-dependent; refer to Certificate of Analysis)
Sequence: Tyr-{Aib}-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{α-Me-Leu}-Leu-Asp-Lys-{diacid-C20-gamma-Glu-(AEEA)-Lys}-Ala-Gln-{Aib}-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂
Form: Lyophilized powder
Storage: Store at ≤ -20°C in a cool, dry place, protected from light and moisture
Solubility: Soluble in sterile water and DMSO; prepare working solutions per laboratory protocol