OVIOPEPTIDES

Exclusive Offer

Free Bacteriostatic Water

Sign up and get a free bacteriostatic water added to your next order, automatically.

Research Use OnlyGet free bacteriostatic water added to your next order when you join the list.

Retatrutide vs Tirzepatide — Canada Research Comparison

By Dr. Elena Morozova, PhDReviewed by Dr. Elena Morozova, PhDPublished April 11, 2026Last reviewed April 11, 20262 min read
Quick answer

Retatrutide is an investigational GLP-1 / GIP / glucagon triple agonist in Phase 3, while tirzepatide is a Health Canada approved GLP-1 / GIP dual co-agonist marketed as Mounjaro and Zepbound.

At a glance

Retatrutide and tirzepatide are both engineered incretin-class peptides from Eli Lilly. They share a GLP-1 / GIP backbone but diverge on a single critical point: retatrutide adds glucagon receptor agonism, producing a balanced triple agonist, while tirzepatide stops at the dual receptor profile. That one change shifts retatrutide from an appetite-and-insulin compound to an appetite-and-energy-expenditure compound.

Key facts

FeatureRetatrutide (LY3437943)Tirzepatide (LY3298176)
ClassGLP-1 / GIP / glucagon triple agonistGLP-1 / GIP dual co-agonist
Receptors activatedGLP-1R, GIPR, GCGRGLP-1R, GIPR
DeveloperEli LillyEli Lilly
Approval (Canada)None — Phase 3Mounjaro (T2D), Zepbound (obesity)
Key trialPhase 2, Jastreboff NEJM 2023SURMOUNT-1, Jastreboff NEJM 2022
Reported weight loss~24.2% at 48w (12 mg)~20.9% at 72w (15 mg)
DosingOnce weekly SCOnce weekly SC
Current programmeTRIUMPH Phase 3SURPASS / SURMOUNT completed

Mechanism contrast

Tirzepatide is built from a GIP backbone with modifications that produce balanced GLP-1R / GIPR co-agonism. The GLP-1 arm drives glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and central appetite reduction. The GIP arm potentiates insulin release and modulates adipose fatty-acid handling.

Retatrutide preserves both of those arms and adds glucagon receptor activation. In preclinical and early human data, glucagon agonism is associated with increased hepatic fatty-acid oxidation and elevated resting energy expenditure — effects that oppose the weight-sparing side of pure glucagon, which normally raises blood glucose. Combining glucagon with GLP-1 appears to neutralise the hyperglycaemic risk while retaining the thermogenic and hepatic-lipid benefits.

Evidence quality

Tirzepatide has a complete Phase 3 dataset (SURPASS for type 2 diabetes, SURMOUNT for obesity) and Health Canada marketing authorisation. Retatrutide is supported by a single published Phase 2 trial in obesity (Jastreboff et al., NEJM 2023) plus interim Phase 2 data in type 2 diabetes and MASLD. The Phase 3 TRIUMPH programme is ongoing — readouts expected from 2025 onward. No cardiovascular outcomes trial has reported for retatrutide.

Regulatory status

Only tirzepatide is a Health Canada approved prescription drug. Research- grade retatrutide and tirzepatide sold as laboratory chemicals are separate, unapproved forms for non-clinical research use only.

Frequently asked questions

What is the core mechanistic difference between retatrutide and tirzepatide?
Tirzepatide is a dual agonist at the GLP-1 and GIP receptors. Retatrutide adds a third arm — glucagon receptor agonism — which is associated in preclinical models with increased energy expenditure and reduced hepatic lipid content. The glucagon arm is the defining feature that distinguishes retatrutide from every other incretin-class peptide currently in development.
Is retatrutide approved in Canada?
No. Retatrutide (LY3437943) is an Eli Lilly investigational compound currently in the Phase 3 TRIUMPH programme. It has no marketing authorisation from Health Canada, the U.S. FDA, or any other regulator. Tirzepatide, by contrast, is Health Canada approved as Mounjaro for type 2 diabetes and Zepbound for chronic weight management.
How do reported weight reductions compare?
In the Phase 2 trial by Jastreboff et al. (NEJM 2023), retatrutide 12 mg once weekly produced mean weight reduction of approximately 24.2% at 48 weeks in adults with obesity. In the SURMOUNT-1 Phase 3 trial, tirzepatide 15 mg once weekly produced mean weight reduction of approximately 20.9% at 72 weeks. Cross-trial comparisons should be interpreted cautiously because of differences in duration, dosing, and population.
Can Canadian researchers purchase either compound?
Both are sold in Canada by licensed research-chemical suppliers as laboratory reagents for non-clinical research use only. Neither research-grade material is a substitute for the approved prescription product, and neither is intended for human administration.

References

  1. [1]Jastreboff AM, Kaplan LM, Frías JP, et al.. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023. DOI: 10.1056/NEJMoa2301972
  2. [2]Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 2022. DOI: 10.1056/NEJMoa2206038
  3. [3]Frías JP, Davies MJ, Rosenstock J, et al.. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). New England Journal of Medicine, 2021. DOI: 10.1056/NEJMoa2107519
  4. [4]National Center for Biotechnology Information. PubChem CID 156588324 — Tirzepatide, 2024

Related research