Retatrutide (LY-3437943) — Canada Research Brief

Mechanism

Retatrutide is a 39-amino-acid synthetic peptide that simultaneously activates three receptors involved in glucose and energy homeostasis:

• GLP-1 receptor — enhances glucose-dependent insulin secretion, slows gastric emptying, and reduces appetite centrally.
• GIP receptor — potentiates insulin secretion in the presence of hyperglycaemia and contributes to adipose-tissue handling of fatty acids.
• Glucagon receptor — increases energy expenditure and hepatic thermogenesis, offsetting some of the fat-storage effects seen with incretin-only agonists.

Adding glucagon receptor activity to the familiar GLP-1 / GIP backbone is what distinguishes retatrutide from tirzepatide. In the phase-2 READY 1 trial (Jastreboff et al., NEJM 2023), retatrutide produced mean placebo- adjusted weight reductions of up to −22.1% at 48 weeks in the 12 mg cohort — the largest mean reduction reported for any peptide drug candidate at the time of publication.

Clinical trial status

As of publication, retatrutide is in phase-3 trials for obesity (TRIUMPH program) and type 2 diabetes, sponsored by Eli Lilly. None of these trials are complete. Retatrutide is not approved by Health Canada, the FDA, the EMA, or any other regulator. Its availability as a research peptide is based on its status as a synthesisable compound with a published structure, not on any approved clinical use.

How Canadian researchers source retatrutide

Canadian labs sourcing retatrutide should verify three things on any vendor: (1) per-batch HPLC purity ≥98%, (2) mass spectrometry confirming a molecular weight of 4,731.41 g/mol, and (3) domestic Canadian shipping to avoid CBSA holds on international incretin peptide shipments.

Comparisons

• Retatrutide vs tirzepatide — head-to-head on mechanism, potency, and clinical data.
• Retatrutide vs semaglutide — single-agonist versus triple-agonist trade-offs.

Regulatory framing in Canada

Retatrutide is not a Health Canada approved drug, not a prescription item, and not a natural health product. It is sold in Canada only as a research chemical under the non-clinical-use framing described in our peptides in Canada guide.