Retatrutide vs Cotadutide
Side-by-Side Comparison
| Attribute | Retatrutide | Cotadutide |
|---|---|---|
| Category | Metabolic / Triple Agonist | Metabolic / Dual GLP-1/Glucagon Agonist |
| Mechanism | Retatrutide simultaneously activates three receptors: GLP-1 (reduces appetite, slows gastric emptying, improves insulin secretion), GIP (enhances insulin sensitivity, glucose control), and glucagon... | Cotadutide is a synthetic peptide that activates both the GLP-1 receptor and the glucagon receptor in a balanced ratio. |
| Evidence Rating | B — Phase III / NDA Filed | C — Phase I–II Clinical Trials |
| Clinical Status | Phase 3 clinical trials (Eli Lilly TRIUMPH program) | Phase II completed for T2D, obesity, and NASH/MASH. Development status uncertain; AstraZeneca has not advanced to Phase III. |
| Safety Profile | GI side effects (dose-related, 13-63% across dose groups): nausea, vomiting, diarrhea, constipation; mostly mild to moderate; GI events partially mitigated with lower starting dose (2 mg vs 4 mg initial dose) | Common: nausea, vomiting, diarrhea, decreased appetite (GLP-1 class effects); GI adverse events are dose-dependent; titration helps manage tolerability |
| Route | Subcutaneous (clinical trial formulation only) | Subcutaneous |
| Dose Range | Phase 2 tested 1, 4, 8, 12 mg weekly SC; optimal dose being determined in Phase 3 | 100–300 mcg SC once daily (Phase 2 tested up to 300 mcg) |
| Frequency | Once weekly | Once daily |
| Molecular Weight | N/A | N/A |
| Half-Life | ~6 days (allows once-weekly dosing) | ~12-13 hours (once-daily dosing) |
Overview
Retatrutide and Cotadutide are both research peptides studied across multiple applications. This comparison examines their mechanisms, evidence base, dosing protocols, and safety profiles to help researchers understand the key differences and overlaps.
Retatrutide — Mechanism & Evidence
Retatrutide is a first-in-class investigational triple hormone receptor agonist (GIP, GLP-1, and glucagon) developed by Eli Lilly. In the Phase 2 trial (Jastreboff et al., NEJM 2023, n=338), the 12 mg dose achieved 24.2% mean body weight reduction at 48 weeks, with 100% of participants achieving at least 5% weight loss. Multiple Phase 3 TRIUMPH trials are ongoing, with TRIUMPH-4 (Dec 2025) reporting average loss up to 71.2 lbs with osteoarthritis pain relief. Expected FDA approval is 2027-2028.
Key claims: Unprecedented weight loss in Phase 2; Phase 3 confirms efficacy with osteoarthritis benefit; Improves glycemic control in type 2 diabetes.
Cotadutide — Mechanism & Evidence
Cotadutide (MEDI0382) is a dual GLP-1/glucagon receptor agonist developed by AstraZeneca (originally MedImmune). It is a once-daily injectable peptide designed to combine GLP-1 receptor-mediated glucose lowering and appetite suppression with glucagon receptor-mediated hepatic fat oxidation and energy expenditure. Phase II trials have been completed in type 2 diabetes, obesity, and NASH/MASH. Development status is uncertain after mixed Phase II results and AstraZeneca portfolio prioritization.
Key claims: Reduces liver fat in NASH/MASH; Improves glycemic control in T2D; Produces weight loss.
Shared Research Applications
Both peptides are studied for: Weight Management, Metabolic Health.
Retatrutide is also researched for: no additional unique applications.
Cotadutide is also researched for: no additional unique applications.
Safety Considerations
Retatrutide: GI side effects (dose-related, 13-63% across dose groups): nausea, vomiting, diarrhea, constipation; mostly mild to moderate GI events partially mitigated with lower starting dose (2 mg vs 4 mg initial dose) Dose-dependent heart rate increases peaking at 24 weeks, declining thereafter
Cotadutide: Common: nausea, vomiting, diarrhea, decreased appetite (GLP-1 class effects) GI adverse events are dose-dependent; titration helps manage tolerability Once-daily dosing may produce more GI side effects than weekly formulations due to peak-trough fluctuations
Related Products
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Related Research News
Retatrutide Clinical Trial Results: Phase III TRIUMPH Data Shows Significant Weight Loss
Early reports from the Phase III TRIUMPH-1 trial suggest retatrutide, a novel triple agonist, has delivered substantial weight loss outcomes. These retatrutide clinical trial results indicate a potential shift in obesity treatment research, though full data analysis is pending.
Retatrutide Phase III TRIUMPH-1 Results: Unprecedented Weight Loss Reported at ADA26
Early reports from the American Diabetes Association 2026 meeting suggest retatrutide delivered unprecedented weight loss in the Phase III TRIUMPH-1 trial. Researchers and industry professionals are closely watching these retatrutide clinical trial results for implications in obesity and metabolic disease treatment.
Retatrutide Monthly Research Cost in Australia Breakdown
Researching Retatrutide (LY3437943), the most advanced triple GLP-1/GIP/glucagon receptor agonist, involves costs that vary by vial size, dose, and frequency. In Australia, a 10mg vial costs $129.99 AUD ($13.00/mg), while a 20mg vial is $199.99 AUD ($10.00/mg). Supplies like bacteriostatic water and needles add to monthly expenses, with planning around a 4-week reconstituted stability window essential to minimize waste.