GLP-3 (Retatrutide)

What Is Retatrutide (GLP-3)?

Retatrutide is a novel triple receptor agonist developed by Eli Lilly that simultaneously targets three distinct metabolic pathways: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GcgR). This triple mechanism represents a significant advancement over earlier dual agonists and has generated substantial interest in metabolic research circles.

Unlike semaglutide (GLP-1 monoagonist) or tirzepatide (GLP-1/GIP dual agonist), retatrutide's additional glucagon receptor activity contributes to increased energy expenditure and hepatic lipid mobilization in preclinical and early clinical research models. It remains investigational at the time of this writing and is not FDA-approved for any clinical indication.

Retatrutide is designed as a long-acting peptide with fatty-acid side chains that bind serum albumin, extending its plasma half-life and enabling once-weekly administration in published research protocols.

Research & Published Studies

• Jastreboff et al. (NEJM, 2023): Phase 2 trial in adults with obesity. At 48 weeks, the 12mg dose group achieved a mean body-weight reduction of approximately 24.2% from baseline — the largest weight reduction reported in any obesity pharmacotherapy trial at the time.
• Triple receptor synergy: Preclinical research indicates that glucagon receptor agonism adds energy expenditure benefits beyond what GLP-1 and GIP dual agonism achieves, particularly in hepatic lipid clearance and basal metabolic rate modulation.
• Glycemic research: Phase 2 data in subjects with type 2 diabetes showed HbA1c reductions of approximately 2.0% at higher doses, comparable to tirzepatide, with fasting glucose improvements across all dose cohorts.
• Safety profile: GI adverse events (nausea, diarrhea, vomiting) were the most common findings, consistent with the incretin receptor agonist class. Heart rate increases of 4–7 bpm were observed, slightly higher than dual agonists.

Research Use Cases

• Metabolic pathway research investigating triple incretin receptor agonism
• Comparative studies of GLP-1, dual (GIP/GLP-1), and triple agonist mechanisms
• Energy expenditure and hepatic lipid mobilization models
• Obesity and insulin resistance research protocols
• Body composition research in controlled laboratory settings

Specifications

Related Research Compounds