# Retatrutide vs semaglutide

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

Semaglutide is an FDA-approved GLP-1 receptor agonist with a cardiovascular-outcomes trial behind it [1][2]; retatrutide is an investigational GIP, GLP-1 and glucagon receptor agonist. In their separate obesity trials, retatrutide produced −23.7% to −25.0% at 80 weeks [3] and semaglutide 2.4 mg −14.9% at 68 weeks [4]. No trial cited here compares them directly.

## Side by side
| | Retatrutide | Semaglutide |
|---|---|---|
| Receptors | GIP, GLP-1 and glucagon [3] | GLP-1 [5] |
| FDA status | Investigational | Approved: Ozempic, Wegovy, Rybelsus [6][7] |
| Pivotal obesity trial | TRIUMPH-1: −17.6% to −25.0% vs −3.9%, 80 wk [3] | STEP 1: −14.9% vs −2.4%, 68 wk [4] |
| Cardiovascular outcomes trial | None published | SELECT: MACE 6.5% vs 8.0% [2] |
| Half-life | Weekly dosing in trials [8] | About 7 days [9] |
| Oral form | No | Yes (type 2 diabetes) [10] |
| Evidence grade | B | A |

## How do they work differently?

Semaglutide is a fatty-acid-modified GLP-1 analog acting on the GLP-1 receptor [11][5]. Retatrutide adds agonism at GIP and glucagon receptors [8]. The glucagon component is associated in trials with large liver-fat reductions — 81–82% at the higher doses over 24 weeks [12] — and with a dose-dependent heart-rate rise [8].

## How do weight and metabolic outcomes compare?

Semaglutide 2.4 mg reduced weight by 14.9% versus 2.4% with placebo at 68 weeks in STEP 1 and by 15.2% versus 2.6% at 104 weeks in STEP 5 [4][13]. Retatrutide reduced weight by 17.6%, 23.7% and 25.0% versus 3.9% at 80 weeks in TRIUMPH-1 [3], and by 11.9–18.8% versus 5.1% in people with type 2 diabetes in TRIUMPH-2 [14].

These are separate trials, so the gap between them is not a measured treatment difference. The direct comparison that exists for semaglutide is against tirzepatide (see [semaglutide vs tirzepatide](https://residue.info/vs/semaglutide-vs-tirzepatide/)).

## What outcomes beyond weight have been measured?

Semaglutide's SELECT trial reduced the composite of cardiovascular death, heart attack or stroke from 8.0% to 6.5% in people with cardiovascular disease and obesity but no diabetes [2], and Ozempic is labeled for kidney outcomes in type 2 diabetes with chronic kidney disease [5]. Retatrutide's TRIUMPH-1 reported improvements in knee-osteoarthritis pain and sleep-apnea measures in nested sub-studies [3]; no cardiovascular-outcomes result is published.

## How do their safety records compare?

Both are mainly gastrointestinal in their adverse-event profiles [4][8]. Semaglutide discontinuation for adverse events was 16.6% versus 8.2% on placebo over SELECT's mean 39.8 months [2]. Retatrutide's trials additionally reported heart-rate increases [8] and, in TRIUMPH-2, more hypotension and dysesthesia than placebo [14].

## Are they FDA-approved?

Semaglutide is FDA-approved [6][7][15]. Retatrutide is investigational, with no Drugs@FDA application at our fetch.

## Frequently asked questions
**Does retatrutide cause more weight loss than semaglutide?**
Its own trials show larger placebo-adjusted reductions (TRIUMPH-1, −25.0% at 12 mg) [3] than semaglutide's STEP 1 (−14.9%) [4], but the trials were separate and of different lengths; no head-to-head result is cited here.

**Which has more evidence?**
Semaglutide, by a wide margin: it is approved in injectable and oral forms, has a 17,604-person cardiovascular outcomes trial [2] and two-year weight data [13]. Retatrutide has phase 2 and phase 3 trial reports [8][3].

**Can retatrutide be prescribed?**
Not as an approved drug: Drugs@FDA listed no retatrutide application at our fetch. Semaglutide's approved labels define its uses [5][1].

**Can you take retatrutide and semaglutide together?**
No published trial among the sources we cite tested that combination. Retatrutide is investigational; semaglutide labels describe monotherapy [5][1].

**What are the side effects of retatrutide vs semaglutide?**
Both programs report mostly gastrointestinal events. Retatrutide phase 2 and TRIUMPH reports also note dose-dependent heart-rate increases [8]; semaglutide's SELECT and STEP programs characterize GI events and gallbladder disorders under the approved labels [2][1].


## Sources
[1] WEGOVY prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2024-04-23. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5e548d0-cc79-4c34-a3f5-e20a5b8b6564
[2] Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff AM et al. N Engl J Med. 2023. https://pubmed.ncbi.nlm.nih.gov/37952131/
[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] Once-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding JPH et al. N Engl J Med. 2021. https://pubmed.ncbi.nlm.nih.gov/33567185/
[5] OZEMPIC prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-07-30. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42bdd912-2393-44c4-b7e0-47672ca28991
[6] Drugs@FDA: OZEMPIC (NDA209637). NOVO; original approval 2017-12-05; Prescription, Discontinued. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209637
[7] Drugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215256
[8] 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/
[9] Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Hall S et al. Clin Pharmacokinet. 2018. https://pubmed.ncbi.nlm.nih.gov/29915923/
[10] OZEMPIC, RYBELSUS prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-01-30. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98
[11] Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Jensen L et al. Eur J Pharm Sci. 2017. https://pubmed.ncbi.nlm.nih.gov/28323117/
[12] 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/
[13] Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Garvey WT et al. Nat Med. 2022. https://pubmed.ncbi.nlm.nih.gov/36216945/
[14] 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/
[15] Drugs@FDA: OZEMPIC, RYBELSUS (NDA213051). NOVO; original approval 2019-09-20; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213051

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