How they work
- Tirzepatide is a dual agonist. It activates GLP-1 and GIP receptors, gut hormone pathways that lower appetite, slow stomach emptying and help insulin release when blood sugar is high.
- Retatrutide is a triple agonist. It targets GIP, GLP-1 and glucagon receptors. It's a once-weekly injection in trials.
Both are made by Eli Lilly. Tirzepatide is sold as Zepbound for weight and obstructive sleep apnea and as Mounjaro for type 2 diabetes. Retatrutide is available only to people enrolled in Lilly's clinical trials. For the basics on tirzepatide's class, see is tirzepatide a GLP-1.
What the trials found
| Retatrutide (TRIUMPH-1) | Tirzepatide (Zepbound Study 1) | |
|---|---|---|
| Who | Adults with obesity or overweight | Adults with obesity, or overweight with a weight-related condition, without type 2 diabetes |
| Length | 80 weeks | 72 weeks |
| Average weight change, highest dose | 28.3% | 20.9% |
| Average weight change, placebo | 2.2% | 3.1% |
| Stopped due to side effects, highest dose vs placebo | 11.3% vs 4.9% | 6.7% vs 3.4% (pooled weight trials) |
Other retatrutide Phase 3 results, July 2026: in TRIUMPH-2 (adults with type 2 diabetes), weight fell up to 20.8% at 80 weeks versus 4.0% on placebo. In TRIUMPH-3 (severe obesity with heart disease), up to 22.6% versus 3.2%.
The direct comparison is TRIUMPH-5, a Phase 3, double-blind trial of retatrutide versus tirzepatide in about 800 adults with obesity. ClinicalTrials.gov lists its estimated primary completion as November 2026. Until those results are out, no one can say how the two compare in the same people.
Side effects
| Side effect | Retatrutide (TRIUMPH-1, by dose) | Zepbound (by dose) |
|---|---|---|
| Nausea | 28.6% to 42.4% (placebo 14.8%) | 25% to 29% (placebo 8%) |
| Diarrhea | 25.2% to 34.1% (placebo 13.5%) | 19% to 23% (placebo 8%) |
| Vomiting | 10.6% to 25.3% (placebo 4.8%) | 8% to 13% (placebo 2%) |
| Constipation | 23.8% to 26.1% (placebo 10.9%) | 11% to 17% (placebo 5%) |
| Dysesthesia (unusual skin sensations) | 5.1% to 12.5% (placebo 0.9%) | 0.2% to 0.4% (placebo 0.1%) |
Both cause mostly stomach-related side effects. Lilly reported that retatrutide's skin-sensation and urinary tract infection events were mostly mild to moderate and resolved during treatment. Retatrutide's full safety profile won't be known until the FDA reviews it. Tirzepatide's label lists its serious warnings; see tirzepatide side effects.
Is retatrutide FDA-approved? Can I get it?
No. As of October 2026, retatrutide is not FDA-approved for any use. Lilly's July 2026 release said it plans to submit retatrutide for U.S. approval in the first quarter of 2027. That is a plan, not an approval, and FDA review takes time after a submission.
Don't buy retatrutide online. The FDA has warned companies selling retatrutide labeled "for research purposes" or "not for human consumption." These products are unapproved and of unknown quality, and federal law doesn't allow retatrutide to be used in compounding.
The legal way to take retatrutide today is through a clinical trial. You can search open studies on ClinicalTrials.gov and ask your clinician whether one fits.
What to do now
If you want a weight medicine today, the choice is among approved options like tirzepatide and semaglutide. Waiting for retatrutide means waiting at least until FDA review is complete, with no set date. A clinician can help weigh your options now.
Through Gabriel, a licensed clinician reviews every prescription request and decides whether tirzepatide or semaglutide is appropriate. See how much tirzepatide costs and tirzepatide vs semaglutide.
Common questions
Is retatrutide better than tirzepatide?
Retatrutide produced more average weight loss in its own trials, but there are no head-to-head results yet. TRIUMPH-5, which compares them directly, has an estimated primary completion of November 2026.
Is retatrutide FDA-approved?
No. As of October 2026 it is investigational. Lilly plans to submit it for U.S. approval in the first quarter of 2027.
When will retatrutide be available?
Not before the FDA approves it. Lilly plans to file in early 2027, and review takes months after that. No approval date has been set.
What is the difference between tirzepatide and retatrutide?
Tirzepatide activates GIP and GLP-1 receptors. Retatrutide also activates the glucagon receptor. Tirzepatide is approved; retatrutide isn't.
Is it safe to buy retatrutide online?
No. Any retatrutide sold to the public is unapproved, and the FDA has warned sellers of products labeled "for research" that are of unknown quality.
Sources
- Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (May 21, 2026) Eli Lilly (PR Newswire)
- Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (July 23, 2026) Eli Lilly (PR Newswire)
- Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea (June 6, 2026) Eli Lilly (PR Newswire)
- A Study of Retatrutide Compared to Tirzepatide in Adults Who Have Obesity (TRIUMPH-5, NCT06662383) ClinicalTrials.gov
- Zepbound (tirzepatide) prescribing information, revised 08/2026 Eli Lilly
- FDA's concerns with unapproved GLP-1 drugs used for weight loss U.S. Food and Drug Administration
This guide is general information, not medical advice. It does not replace a visit with a licensed clinician. Gabriel membership is not health insurance.