Semaglutide vs retatrutide
Semaglutide is an approved GLP-1 drug with years of outcome data. Retatrutide is an investigational triple-receptor drug whose trials show larger weight losses. No head-to-head results have been published.
- Semaglutide
- Approved drugOnce weekly
- Retatrutide
- Human studiesOnce weekly
- Head-to-head trials
- None published
The short answer
Semaglutide (Wegovy, Ozempic) activates one receptor, GLP-1. Retatrutide activates three: GIP, GLP-1 and glucagon. Both are once-weekly injections stepped up over about 16 weeks.
In separate trials, semaglutide 2.4 mg lowered weight 14.9% at 68 weeks (STEP 1) and retatrutide 12 mg 25.0% at 80 weeks (TRIUMPH-1), counting everyone who started. The trials differ in length and population, so the gap isn’t a measured difference. Semaglutide has outcome trials showing fewer heart attacks, strokes and kidney events; retatrutide isn’t approved yet.
At a glance
| Field | SemaglutideActive ingredient in Ozempic and Wegovy | RetatrutideLY3437943 |
|---|---|---|
| Evidence | Approved drug | Human studies |
| Class | GLP-1 receptor agonist | GIP / GLP-1 / glucagon triple agonist |
| Approval | Approved in the US as Wegovy (weight management, heart risk, MASH) and as Ozempic and Rybelsus (type 2 diabetes), as weekly injections and daily tablets. | Not approved anywhere; in Phase 3 trials. Lilly said in July 2026 it plans to file with FDA in the first quarter of 2027. |
| Sport (WADA 2026) | Not banned in sport | Likely banned in sport |
| Common dose | 0.25 → 2.4 mg weekly | 2 → 12 mg weekly |
| Frequency | Once weekly | Once weekly |
| Cycle | Continuous | Continuous |
| Route | Subcutaneous injection | Subcutaneous injection |
| Half-life | about 1 week Label | about 6 days Trial |
| Typical draw | 5 units10 mg with 2 mL, 0.25 mg | 10 units40 mg with 2 mL, 2 mg |
| Vial sizes or form | 10, 20 mg | 5, 10, 20, 30, 40, 50, 60 mg |
| Human studies | 5 listedLargest: 17,604 people (2023) | 5 listedLargest: 2,339 people (2026) |
| Main cautions |
|
|
| Open Semaglutide | Open Retatrutide |
Doses shown are what labels, trials or community reports reference, not recommendations. Each compound’s page has the full detail and sources.
Key differences
How they work
Semaglutide: GLP-1 receptor. Retatrutide: GIP, GLP-1 and glucagon receptors.
Track record
TrialSemaglutide was first approved in 2017. Its outcome trials found fewer heart attacks, strokes and cardiovascular deaths (SELECT, SUSTAIN-6) and fewer major kidney events (FLOW). Retatrutide’s first Phase 3 results came in December 2025, and Lilly plans to file with FDA in early 2027.
Weight loss in trials
TrialSemaglutide 2.4 mg: 14.9% at 68 weeks (STEP 1); 7.2 mg: 18.7% at 72 weeks (STEP UP). Retatrutide 4, 9 and 12 mg: 17.6%, 23.7% and 25.0% at 80 weeks (TRIUMPH-1).
Doses
Semaglutide steps up from 0.25 mg to 2.4 mg over 16 weeks (Wegovy label). Retatrutide’s Phase 3 trials stepped up from 2 mg every 4 weeks to 4, 9 or 12 mg.
Side effects
Both cause dose-related nausea, diarrhea, vomiting and constipation, and both raise heart rate. Skin sensitivity (dysesthesia) shows up at high doses of both: 22% on semaglutide 7.2 mg (label) and about 12% on retatrutide 9–12 mg (TRIUMPH-1).
In sport
Semaglutide isn’t banned; WADA tracks it in its Monitoring Program. Retatrutide is likely banned at all times under WADA’s S0 rule.
Head-to-head studies
Taking them together
Semaglutide and retatrutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist.
Source: Wegovy and Zepbound prescribing information, section 1
Open them in the stack check for sport status and one combined tracking checklist.
Questions
What is the difference between semaglutide and retatrutide?
Semaglutide (Wegovy, Ozempic) activates one receptor, GLP-1. Retatrutide activates three: GIP, GLP-1 and glucagon. Both are once-weekly injections stepped up over about 16 weeks.
Is retatrutide better than semaglutide?
Retatrutide’s trials report larger weight losses than semaglutide’s, but no published trial has compared them directly, and retatrutide isn’t approved. Semaglutide has the longer safety record and outcome trials showing fewer heart and kidney events.
Can semaglutide and retatrutide be taken together?
The stack check flags two GLP-1 drugs. Semaglutide and retatrutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist. No published study has tested them together.
Which has more evidence in people, semaglutide or retatrutide?
Semaglutide is approved in the US; its page lists 5 key human studies. Retatrutide is in clinical trials and not approved; its page lists 5 key human studies. They haven’t been compared directly in a published trial.
Are semaglutide and retatrutide banned in sport?
Retatrutide is likely banned under WADA’s S0 rule for unapproved drugs. Semaglutide isn’t banned. This follows the WADA 2026 Prohibited List; athletes should confirm with their anti-doping organization.
Sources
- TRANSCEND-T2D-2, retatrutide compared with semaglutide in type 2 diabetes: ClinicalTrials.gov registry entry NCT06260722
- Wilding et al., semaglutide for obesity, STEP 1 (NEJM 2021) PMID 33567185
- Jastreboff et al., retatrutide for obesity, TRIUMPH-1 (NEJM 2026) PMID 42814954
- Lincoff et al., semaglutide and cardiovascular outcomes, SELECT (NEJM 2023) PMID 37952131
- Wegovy prescribing information, rev. 06/2026 (Novo Nordisk)
Each compound’s page lists its full sources: Semaglutide, Retatrutide.