# Retatrutide vs tirzepatide

- Canonical: https://residue.info/vs/retatrutide-vs-tirzepatide/
- Compounds: Retatrutide (https://residue.info/c/retatrutide/), Tirzepatide (https://residue.info/c/tirzepatide/)
- Updated: 2026-10-19 · Reviewed by: Residue Editorial Team

Tirzepatide activates GIP and GLP-1 receptors and is FDA-approved [1][2]; retatrutide adds the glucagon receptor and is still investigational. In separate placebo-controlled trials, retatrutide produced −23.7% to −25.0% at 80 weeks [3] and tirzepatide −15.0% to −20.9% at 72 weeks [4]. No trial cited here compares them directly.

## Side by side
| | Retatrutide | Tirzepatide |
|---|---|---|
| Receptors | GIP, GLP-1 and glucagon [3] | GIP and GLP-1 [1] |
| FDA status | Investigational; no Drugs@FDA application | Approved: Mounjaro, Zepbound [5][6] |
| Pivotal obesity trial | TRIUMPH-1: −17.6% to −25.0% vs −3.9%, 80 wk [3] | SURMOUNT-1: −15.0% to −20.9% vs −3.1%, 72 wk [4] |
| Obesity with type 2 diabetes | TRIUMPH-2: −11.9% to −18.8% vs −5.1%, 80 wk [7] | SURPASS-2: weight −1.9 to −5.5 kg more than semaglutide 1 mg [8] |
| Liver fat | −81% to −82% at 24 wk (MRI sub-study) [9] | Not a labeled use |
| Common adverse events | Gastrointestinal, dose-related; heart rate rise [10] | Nausea 12–24%, diarrhea 12–22% across SURPASS [11] |
| Evidence grade | B | A |

## How do they work differently?

Tirzepatide is a single peptide with agonist activity at the GIP and GLP-1 receptors, as stated in both its labels [1][2]. Retatrutide (LY3437943) extends the idea to a third receptor, glucagon [10]. In retatrutide's MRI sub-study, liver fat fell by 81–82% at the 8 and 12 mg doses, and 79–86% of participants reached normal liver fat below 5% [9].

## How much weight was lost in their own trials?

**Retatrutide.** In the 48-week phase 2 trial of 338 adults with obesity, weight changed by −24.2% at 12 mg and −22.8% at 8 mg versus −2.1% on placebo [10]. In phase 3 TRIUMPH-1 (2,339 adults with obesity, no diabetes), 80-week weight change was −17.6%, −23.7% and −25.0% at 4, 9 and 12 mg versus −3.9% [3]. TRIUMPH-2, in 1,152 adults with obesity and type 2 diabetes, found −11.9%, −16.8% and −18.8% versus −5.1% [7].

**Tirzepatide.** SURMOUNT-1 found −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg versus −3.1% at 72 weeks, with 57% of the 15 mg group losing 20% or more [4]. In the only head-to-head obesity trial against semaglutide, tirzepatide reached −20.2% versus −13.7% [12].

Cross-trial comparison is unreliable: the trials ran for different lengths, used different escalation schedules and enrolled different people. Our [methodology](https://residue.info/methodology/) does not grade one drug against another on cross-trial numbers.

## How do their safety records compare?

Gastrointestinal adverse events dominate both programs. Across SURPASS-1 to -5, tirzepatide produced nausea in 12–24%, diarrhea in 12–22% and vomiting in 2–13%, mostly transient and mild to moderate [11]. Retatrutide's adverse events were mostly gastrointestinal and dose-related, and heart rate rose in a dose-dependent way, peaking at 24 weeks [10]; in TRIUMPH-2, hypotension and dysesthesia were also more frequent than with placebo [7].

## Are they FDA-approved?

Tirzepatide is approved for type 2 diabetes, chronic weight management and obstructive sleep apnea with obesity [1][2]. Retatrutide had no Drugs@FDA application at our fetch and remains investigational.

## Can you take retatrutide and tirzepatide together?

No published trial among the sources we cite tested them together. Retatrutide remains investigational; tirzepatide is labeled for use as a single agent [5][2].

## Frequently asked questions
**Is retatrutide better than tirzepatide?**
There is no head-to-head result among the trials we cite. Placebo-adjusted weight loss was larger in retatrutide's TRIUMPH-1 [3] than in tirzepatide's SURMOUNT-1 [4], but the trials differed in duration (80 vs 72 weeks), population and dose schedules.

**Is retatrutide FDA-approved?**
No. Drugs@FDA listed no retatrutide application at our fetch; tirzepatide is approved as Mounjaro and Zepbound [5][6].

**What does the glucagon receptor add?**
Retatrutide is designed to activate glucagon receptors as well as GIP and GLP-1. In trials it reduced liver fat by more than 80% at the higher doses [9]; it also raised heart rate in a dose-dependent way, peaking at 24 weeks [10].

**Do they have the same side effects?**
Both are mostly gastrointestinal [10][11]. In TRIUMPH-2, hypotension and dysesthesia were also more frequent with retatrutide than placebo [7].

**Can you take retatrutide and tirzepatide together?**
No published trial among the sources we cite tested them together. Retatrutide is still investigational; tirzepatide is labeled for use as a single agent [5][2].

**Is retatrutide better than tirzepatide for weight loss?**
There is no head-to-head result among the trials we cite. Placebo-controlled weight loss was larger in retatrutide TRIUMPH-1 (−23.7% to −25.0% at 80 weeks) [3] than in tirzepatide SURMOUNT-1 (−15.0% to −20.9% at 72 weeks) [4], but populations and schedules differed.


## Sources
[1] MOUNJARO, MOUNJARO KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-27. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0
[2] ZEPBOUND, ZEPBOUND KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-28. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
[3] Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. Jastreboff AM et al. N Engl J Med. 2026. https://pubmed.ncbi.nlm.nih.gov/42814954/
[4] Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff AM et al. N Engl J Med. 2022. https://pubmed.ncbi.nlm.nih.gov/35658024/
[5] Drugs@FDA: MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR) (NDA215866). ELI LILLY AND CO; original approval 2022-05-13; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215866
[6] Drugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217806
[7] Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Bellido V et al. Lancet. 2026. https://pubmed.ncbi.nlm.nih.gov/42810372/
[8] Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Frías JP et al. N Engl J Med. 2021. https://pubmed.ncbi.nlm.nih.gov/34170647/
[9] Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Sanyal AJ et al. Nat Med. 2024. https://pubmed.ncbi.nlm.nih.gov/38858523/
[10] Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff AM et al. N Engl J Med. 2023. https://pubmed.ncbi.nlm.nih.gov/37366315/
[11] Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials. Patel H et al. Diabetes Obes Metab. 2024. https://pubmed.ncbi.nlm.nih.gov/37853960/
[12] Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ et al. N Engl J Med. 2025. https://pubmed.ncbi.nlm.nih.gov/40353578/

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