Compound comparison
Retatrutide and tirzepatide are Eli Lilly incretin-based drugs with different receptor targets and regulatory status. Tirzepatide is a dual GIP and GLP-1 receptor agonist with FDA-approved indications. Retatrutide activates GIP, GLP-1, and glucagon receptors and remains investigational. Its Phase 2 12 mg group had a mean body-weight change of -17.5% at week 24 and -24.2% at week 48. Lilly reported positive TRIUMPH-1 Phase 3 obesity results in 2026, but no approval decision had occurred by the July 12 review cutoff. Results from separate trials are not head-to-head evidence.
Scope: Receptor pharmacology, FDA status, evidence stage, and reported obesity-trial outcomes.
Data cutoff: 2026-07-12
Cross-trial warning: Results from separate trials do not establish a head-to-head difference.
Limits: Most outcome figures come from separate trials with different populations, durations, doses, estimands, and review status. They cannot establish comparative superiority.
| Attribute | Retatrutide | Tirzepatide |
|---|---|---|
| Mechanism | Triple receptor agonist: GLP-1, GIP, and glucagon receptor agonism; current clinical trials do not isolate the contribution of each receptor | Dual receptor agonist: GIP and GLP-1 receptor agonism; does not target glucagon receptors |
| Receptor targets | GLP-1, GIP, and glucagon receptors (three simultaneous targets) | GLP-1 and GIP receptors (two simultaneous targets) |
| Developer | Eli Lilly | Eli Lilly |
| FDA approval status | Not FDA-approved for any indication; investigational only | FDA-approved as Mounjaro for Type 2 diabetes and as Zepbound for chronic weight management and moderate-to-severe obstructive sleep apnea in adults with obesity |
| Clinical trial stage | Phase 3 program; TRIUMPH-1 is NCT05929066; Phase 2 published in NEJM in 2023 | Post-approval; multiple Phase 3 trials completed, and SURPASS-CVOT reported cardiovascular outcomes in 2025 |
| Key weight loss evidence | Phase 2 12 mg group: -17.5% at week 24 and -24.2% at week 48; Lilly reported positive Phase 3 obesity results in 2026 | SURMOUNT-1 Phase 3 trial: 22.5% mean weight loss at 72 weeks at the highest dose (Jastreboff et al., NEJM 2022) |
| Approved indications | None (investigational) | Type 2 diabetes (Mounjaro), chronic weight management (Zepbound), and moderate-to-severe obstructive sleep apnea in adults with obesity (Zepbound) |
| Regulatory availability | Investigational; access is limited to authorized clinical research | Available by prescription for FDA-approved indications |
| Additional metabolic effects | Includes glucagon receptor agonism, but current clinical trials do not isolate how much each receptor contributes to the observed outcomes | No glucagon receptor activity; metabolic effects are mediated through GLP-1 and GIP pathways |
Retatrutide (LY3437943) is an investigational triple receptor agonist developed by Eli Lilly that targets GLP-1, GIP, and glucagon receptors. The glucagon component distinguishes it from tirzepatide, but the contribution of each receptor to clinical outcomes cannot be isolated from the current trials.
The Phase 2 trial published in NEJM reported mean body-weight change of -17.5% at week 24 and -24.2% at week 48 in the 12 mg group. Lilly later reported positive TRIUMPH-1 Phase 3 obesity results, which were sponsor-reported at this review cutoff.
Retatrutide is not FDA-approved for any indication. ClinicalTrials.gov identifies TRIUMPH-1 as NCT05929066. FDA states that retatrutide cannot be used in compounding under federal law.
Tirzepatide is a dual GIP and GLP-1 receptor agonist developed by Eli Lilly. It was FDA-approved as Mounjaro in May 2022 for Type 2 diabetes and as Zepbound in November 2023 for chronic weight management.
The SURMOUNT-1 Phase 3 trial, published in NEJM (Jastreboff et al., 2022), demonstrated a mean weight loss of 22.5% at 72 weeks at the highest dose. The SURPASS-2 trial showed superior A1C reduction versus semaglutide in Type 2 diabetes patients.
Tirzepatide is available by prescription for its FDA-approved indications. FDA added moderate-to-severe obstructive sleep apnea in adults with obesity to the Zepbound indication in December 2024. SURPASS-CVOT later found tirzepatide noninferior to dulaglutide for major adverse cardiovascular events in adults with Type 2 diabetes and established atherosclerotic cardiovascular disease.
Tirzepatide has FDA-approved indications. Retatrutide remained investigational at the July 12, 2026 review cutoff. Retatrutide's Phase 2 result at 12 mg was -17.5% at week 24 and -24.2% at week 48, and Lilly later reported positive Phase 3 obesity results. These figures come from different studies, populations, durations, and analysis plans, so they do not establish that one drug is better than the other. This page documents evidence stage and regulatory status without providing treatment guidance.
Related compounds: Retatrutide · Tirzepatide
Source records are stored in the repo and linked from this comparison.
Retatrutide phase 2 obesity trial (NEJM 2023): at 12 mg, mean body weight fell 17.5% at week 24 and 24.2% at week 48; GI adverse events were most common.
nejm-retatrutide-phase2-2023Completed Phase 3 master protocol NCT05929066. The registry identifies TRIUMPH-1 as a randomized, double-blind, placebo-controlled study in adults without type 2 diabetes who have obesity or overweight.
clinicaltrials-retatrutide-triumph1Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. News release, 2026-05-21.
research-reta-04Phase 3 trial of tirzepatide for obesity showing mean weight loss of 22.5% at 72 weeks at the highest dose.
nejm-tirzepatide-surmount1-2022ClinicalTrials.gov registry for the SURMOUNT-1 Phase 3 trial of tirzepatide for obesity, sponsored by Eli Lilly.
clinicaltrials-gov-surmount1FDA approval of Mounjaro (tirzepatide) injection for Type 2 diabetes, NDA 215866.
fda-mounjaro-approval-2022FDA approved Zepbound (tirzepatide) in November 2023 for chronic weight management in adults with obesity, used with diet and exercise. NDA 217806.
fda-zepbound-approval-2023FDA approval announcement adding moderate-to-severe obstructive sleep apnea in adults with obesity to Zepbound's indications.
fda-zepbound-osa-approval-2024SURPASS-CVOT publication reporting that tirzepatide was noninferior to dulaglutide for major adverse cardiovascular events in adults with Type 2 diabetes and established atherosclerotic cardiovascular disease.
pubmed-surpass-cvot-2025FDA warning letter discussing peptide products marketed online and the limits of research-use-only positioning.
fda-gram-peptides-warning-2026Huberman Lab discussion on GLP-1 mechanism. Tracked as expert media signal for public understanding.
youtube-huberman-glp1-2025