Retatrutide

Retatrutide (LY3437943) is an investigational peptide developed by Eli Lilly that acts as a triple agonist at the GLP-1, GIP, and glucagon receptors. It is currently in Phase 3 clinical trials for obesity and related metabolic conditions.

Mechanism

• GLP-1 receptor agonism. Slows gastric emptying, reduces appetite, enhances glucose-dependent insulin secretion.
• GIP receptor agonism. Additional metabolic effects on insulin secretion and adipose tissue.
• Glucagon receptor agonism. The differentiating third arm — increases energy expenditure via hepatic glucagon signaling.

Common research protocols

Dosing information below reflects published research literature. It is not medical advice and is not a treatment plan.

• Clinical trial dosing. Weekly subcutaneous injection with dose titration over multiple weeks. Phase 2 tested doses from 1 mg up to 12 mg weekly.
• Status. Not yet FDA-approved. In active Phase 3 trials as of publication.

Evidence at a glance

• Human data. Phase 2 trial published in the New England Journal of Medicine (Jastreboff et al., 2023) reported mean weight reduction of approximately 24% at the 12 mg dose over 48 weeks.
• Known side effects. Similar to the GLP-1 class: nausea, diarrhea, vomiting, particularly during titration.
• Unknowns. Long-term safety, effects on non-metabolic outcomes, cardiovascular outcomes trials in progress.

Reconstitution & handling

Lyophilized peptides ship as freeze-dried powder. Reconstitute with bacteriostatic water; refrigerate the reconstituted vial. Use the reconstitution calculator to get syringe-unit readings for your target dose. General reconstitution and syringe guidance in the How It Works page.

Primary-literature list for this guide available on request via contact.