Retatrutide vs Zepbound
Which Is Right for You? Complete Comparison (2026)
A look at the weight loss titans: Zepbound (Tirzepatide) vs the experimental Retatrutide. Which one burns more fat?
Retatrutide vs Zepbound: At a Glance
Retatrutide
- ✓Triple agonist: GIP + GLP-1 + glucagon receptors
- ✓Glucagon component increases energy expenditure and fat oxidation
- ✓~24% weight loss at 48 weeks in phase 2 (12 mg dose)
- ✓Phase 3 trials ongoing — not yet FDA-approved
- ✓Developed by Eli Lilly
Zepbound
- ✓Dual GIP + GLP-1 receptor agonist — first in class
- ✓GIP agonism enhances insulin sensitivity in adipose tissue
- ✓~21% mean weight loss at 72 weeks (SURMOUNT-1, 15 mg)
- ✓GIP may moderate GI side effects vs GLP-1-only drugs
- ✓Half-life ~5 days — once-weekly injection
Detailed Comparison
| Feature | Retatrutide | Zepbound |
|---|---|---|
| Mechanism | Triple GIP/GLP-1/glucagon receptor agonist | Dual GIP/GLP-1 receptor agonist |
| Dosing | 1-12 mg SC weekly (phase 2 doses) | 2.5-15 mg SC weekly |
| Administration | Subcutaneous injection weekly | Subcutaneous injection weekly |
| Half-life | ~6 days | ~5 days |
| FDA Status | Not FDA-approved — phase 3 clinical trials | FDA-approved: Mounjaro (T2D), Zepbound (obesity) |
| Key Trial | Jastreboff AM et al. NEJM 2023 — phase 2 obesity trial | Jastreboff AM et al. NEJM 2022 (SURMOUNT-1) — 20.9% weight loss |
| Side Effects | Nausea, diarrhea, vomiting, constipation (similar to other incretins) | Nausea (31%), vomiting, diarrhea, constipation |
Which Should You Choose?
Retatrutide (triple gip/glp-1/glucagon receptor agonist) and Tirzepatide (dual gip/glp-1 receptor agonist) serve different clinical roles despite both being in the Triple incretin agonist space. Retatrutide first triple incretin agonist targeting gip, glp-1, and glucagon receptors. Tirzepatide first-in-class dual gip and glp-1 receptor agonist that activates two incretin pathways for enhanced weight loss and glycemic control vs single agonists.
Whichever you choose, track your protocol in Shotlee to build clean data for dose optimization and outcomes comparison.
Track Both in Shotlee
Shotlee supports tracking any medication or peptide. Compare your results across different protocols with clean dose logs and outcome data.
Retatrutide vs Zepbound: Common Questions
Retatrutide is a triple gip/glp-1/glucagon receptor agonist while Tirzepatide is a dual gip/glp-1 receptor agonist. They differ in mechanism, dosing, and clinical evidence. Your choice should depend on your specific goals and medical history.
Switching should be done under medical supervision. Your prescriber can advise on transition protocols. Track both in Shotlee for comparison data.
Retatrutide works as a triple gip/glp-1/glucagon receptor agonist (1-12 mg SC weekly (phase 2 doses)), while Tirzepatide is a dual gip/glp-1 receptor agonist (2.5-15 mg SC weekly). They have different half-lives (~6 days vs ~5 days), side effect profiles, and levels of clinical evidence.
Yes. Shotlee supports tracking any medication or peptide. You can compare your results across different protocols.
References
- [1]Clinical TrialJastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526.
- [2]Clinical TrialJastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216.
- [3]FDAEli Lilly. Zepbound (tirzepatide) Prescribing Information. U.S. Food and Drug Administration.
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