Retatrutide

Retatrutide (LY3437943) is a novel triple-agonist peptide developed by Eli Lilly that simultaneously targets glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. This multi-receptor approach distinguishes it from single-agonist compounds like semaglutide (GLP-1 only) and dual-agonists like tirzepatide (GIP/GLP-1).

Mechanism of Action

The compound's triple-receptor mechanism produces complementary effects: GLP-1 receptor activation slows gastric emptying and enhances satiety signaling; GIP receptor activation appears to improve insulin sensitivity and lipid metabolism; glucagon receptor activation increases hepatic glucose production acutely while enhancing energy expenditure through thermogenesis and promoting hepatic lipid oxidation (Finan et al., 2015).

Clinical Research

Phase 2 clinical data published in The New England Journal of Medicine demonstrated dose-dependent effects across multiple metabolic parameters at doses ranging from 1mg to 12mg weekly over 48 weeks in 338 participants. The study observed improvements in glycemic parameters, triglyceride levels, and blood pressure measurements (Jastreboff et al., 2023). Phase 3 trials are currently evaluating retatrutide across multiple indications.

Pharmacokinetics

Retatrutide demonstrates a half-life of approximately 6 days, enabling once-weekly subcutaneous administration. Steady-state plasma concentrations are typically achieved by weeks 4-5 of repeated dosing. The extended half-life results from structural modifications including fatty acid acylation, similar to other long-acting incretin analogs.

Safety Profile

Clinical trial data indicates gastrointestinal effects (nausea, diarrhea, vomiting) as the most commonly reported adverse events, consistent with the incretin class mechanism. Dose escalation protocols are typically employed to improve tolerability (Rosenstock et al., 2023).

Research Applications

Retatrutide is of significant interest to researchers studying multi-receptor pharmacology, metabolic pathway interactions, energy homeostasis, and adipose tissue physiology. The compound remains investigational and has not received regulatory approval.

References

1. Jastreboff AM, et al. N Engl J Med. 2023;389(6):514-526.
2. Rosenstock J, et al. Lancet. 2023;402(10401):529-544.
3. Finan B, et al. Nat Med. 2015;21(1):27-36.

This product is supplied exclusively for in vitro research and laboratory investigation. Not intended for human or animal use.