Comparison
Tirzepatide vs Retatrutide: FDA status and research
Tirzepatide vs retatrutide: one is FDA approved, one is experimental. Receptor targets, trial results, half-life, compounding and WADA status.
| Tirzepatide | Retatrutide | |
|---|---|---|
| FDA status | FDA approved. First U.S. approval 2022. Sold as Mounjaro and Zepbound [1, 2] | Not FDA approved. FDA says it has not been found safe and effective for any condition [9] |
| Studied for | Labeled for type 2 diabetes, heart risk in type 2 diabetes, weight reduction and sleep apnea with obesity [1, 2] | Studied for obesity, type 2 diabetes, knee osteoarthritis pain and sleep apnea in phase 2 and 3 trials [3, 6, 7] |
| Route | Under the skin once weekly [1] | Under the skin once weekly in studies [6] |
| Key trials | SURMOUNT-1 (weight), SURPASS-2 (diabetes, vs semaglutide), SURMOUNT-5 [8, 10, 11] | Phase 2 obesity trial, TRIUMPH-1, TRIUMPH-2 [3, 6, 7] |
| Receptors | GIP and GLP-1 receptors [1] | GIP, GLP-1 and glucagon receptors [3] |
| Half-life | About 5 days (label) [1] | About 6 days (phase 1b study) [5] |
| Compounding | Shortage resolved in 2024. Pharmacies may not regularly copy an approved drug [12] | FDA says it cannot be used in compounding under federal law [9] |
| WADA | Not prohibited. Monitored in the 2026 Monitoring Program [14, 15] | Not named. The S0 class bans substances with no approval for human use, so status is unclear [15] |
Tirzepatide and retatrutide come from the same drug family, but their legal status is very different. Tirzepatide is FDA approved as Mounjaro and Zepbound [1, 2]. Retatrutide is experimental. FDA says it is not part of any approved drug and cannot be used in compounding under federal law [9].
One more receptor
Tirzepatide acts on two gut hormone receptors, GIP and GLP-1 [1]. Retatrutide acts on those two plus a third, the glucagon receptor [3]. In lab tests, retatrutide showed balanced activity at the glucagon and GLP-1 receptors and more activity at the GIP receptor [4]. In obese mice, the glucagon part added a rise in energy use on top of lower food intake [4].
Both are given once a week as a shot under the skin. The Mounjaro label gives tirzepatide a half-life of about 5 days [1]. A phase 1b study found a half-life of about 6 days for retatrutide [5].
What the trials tested
Tirzepatide has been through many phase 3 trials and has an FDA label. In SURMOUNT-1, adults with obesity lost 15.0% to 20.9% of body weight over 72 weeks vs 3.1% with placebo [8]. In SURMOUNT-5, it lowered weight more than semaglutide, by 20.2% vs 13.7% [11]. See the tirzepatide page for more trials.
Retatrutide was studied for weight loss in phase 3 TRIUMPH trials, with 4, 9 or 12 mg once weekly for 80 weeks. In TRIUMPH-1, 2,339 adults with obesity without diabetes took part. Weight fell 17.6% to 25.0% with retatrutide vs 3.9% with placebo [6]. In TRIUMPH-2, 1,152 adults with obesity or overweight and type 2 diabetes took part. Weight fell 11.9% to 18.8% vs 5.1% with placebo [7]. TRIUMPH-1 also tested knee pain and sleep apnea in subgroups [6].
No published trial has compared the two drugs directly. The retatrutide phase 3 trials used placebo, not an approved drug, as the comparison [6, 7]. Results from separate trials with different people and lengths should not be compared as if they were head to head [6, 8]. See the retatrutide page for study details.
Safety
Tirzepatide has a boxed warning for thyroid C-cell tumors seen in rats [1]. Its most common side effects are stomach related, such as nausea, diarrhea and vomiting [1].
Retatrutide has no FDA label. In trials, stomach side effects were the most common [3, 7]. In TRIUMPH-2, diarrhea occurred in 27% to 34% of retatrutide groups vs 13% on placebo [7]. In the phase 2 obesity trial, heart rate rose with dose and peaked at 24 weeks [3].
Legal status
FDA declared the tirzepatide shortage resolved in 2024, which ended most compounding of copies [12]. In 2026, FDA also proposed keeping tirzepatide off the 503B bulks list [13].
FDA calls products sold as retatrutide unapproved drugs and has sent warning letters to companies marketing them [9]. Retatrutide does not appear on FDA's 503A nomination list [16]. Check the FDA Peptide Status Tracker for updates.
Frequently asked questions
Is retatrutide FDA approved?
No. FDA says retatrutide is not a component of any FDA-approved drug and has not been found safe and effective for any condition [9].
What is the difference between tirzepatide and retatrutide?
Tirzepatide acts on GIP and GLP-1 receptors [1]. Retatrutide also acts on the glucagon receptor [3].
Has retatrutide been compared directly with tirzepatide?
Not in the published phase 3 trials. TRIUMPH-1 and TRIUMPH-2 compared retatrutide with placebo [6, 7].
Can retatrutide be compounded?
No. FDA says retatrutide cannot be used in compounding under federal law [9].
How much weight loss was seen with retatrutide?
In TRIUMPH-1, weight fell 17.6% to 25.0% over 80 weeks vs 3.9% with placebo [6].
Are tirzepatide and retatrutide banned in sports?
Tirzepatide is not prohibited and is monitored [14, 15]. WADA does not name retatrutide, but its S0 class bans substances with no approval for human use [15].
Sources
- DailyMed: Mounjaro (tirzepatide) injection label
- DailyMed: Zepbound (tirzepatide) injection label
- Jastreboff et al. 2023, NEJM: Retatrutide phase 2 obesity trial (PubMed)
- Coskun et al. 2022, Cell Metab: LY3437943 from discovery to clinical proof of concept (PubMed)
- Urva et al. 2022, Lancet: LY3437943 phase 1b in type 2 diabetes (PubMed)
- Jastreboff et al. 2026, NEJM: TRIUMPH-1 (PubMed)
- Bellido et al. 2026, Lancet: TRIUMPH-2 (PubMed)
- Jastreboff et al. 2022, NEJM: SURMOUNT-1 (PubMed)
- FDA: Concerns with unapproved GLP-1 drugs used for weight loss
- Frías et al. 2021, NEJM: SURPASS-2 (PubMed)
- Aronne et al. 2025, NEJM: SURMOUNT-5 (PubMed)
- FDA: FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize
- FDA: FDA proposes to exclude semaglutide, tirzepatide and liraglutide on 503B bulks list (Apr 30, 2026)
- WADA: 2026 Monitoring Program
- WADA: 2026 Prohibited List
- FDA: Bulk drug substances nominated for use in compounding under section 503A (updated May 14, 2026)