Semaglutide vs Tirzepatide vs Retatrutide

Last updated July 2, 2026 · Medically reviewed by David Chen, MD, PhD

The three leading metabolic peptides differ mainly in how many gut- hormone receptors they engage — and that single design choice cascades into how much weight loss they produce, what side effects they carry, and whether they are approved or still investigational. The table below lays them out side by side.

SemaglutideTirzepatideRetatrutide
NicknameSemaTirzReta
Brand namesOzempic, Wegovy, RybelsusMounjaro, ZepboundNone (Investigational)
DeveloperNovo NordiskEli LillyEli Lilly
Receptors targetedGLP-1GLP-1 + GIPGLP-1 + GIP + glucagon
Headline weight-loss result~14.9% at 68 weeks~22.5% at 72 weeks at 15 mg~28.3% at 80 weeks at 12 mg
FDA status (U.S.)Approved for diabetes and obesityApproved for diabetes and obesityInvestigational, awaiting FDA filing
Most common side effectsGI: nausea, vomiting, diarrheaGI: nausea, vomiting, diarrheaGI effects plus skin tingling at higher doses

How to read the comparison

The pattern tracks receptor count. Semaglutide (GLP-1 only) anchors the low end at ~14.9%. Tirzepatide adds GIP and reaches ~22.5%. Retatrutide adds glucagon on top and leads at ~28.3% — but it is the only one of the three still investigational rather than FDA-approved. More effect and more receptors also tend to mean a slightly broader side-effect profile.

Dig into each on its own page — semaglutide, tirzepatide, and retatrutide — or model their projected results in the dosing calculator.

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