# Retatrutide

- Canonical: https://residue.info/c/retatrutide/
- Also called: LY3437943, Reta, triple G
- Evidence grade: B (Randomized human trials). Randomized phase 2 and phase 3 trials are published in NEJM and The Lancet; no FDA-approved application exists, so the grade stays at B.
- Status: Investigational — not FDA-approved
- PubChem CID: 171390338
- Updated: 2026-10-19 · Reviewed by: Residue Editorial Team

Retatrutide (LY3437943) is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. In the phase 3 TRIUMPH-1 trial, adults with obesity lost a mean 23.7% (9 mg) and 25.0% (12 mg) of body weight at 80 weeks versus 3.9% on placebo [1]. The most common side effects were gastrointestinal [2]. Drugs@FDA lists no approved application for it.

## Key findings
- In the 48-week phase 2 obesity trial (338 adults), mean weight change was −24.2% with 12 mg and −22.8% with 8 mg, versus −2.1% with placebo [3]. (anchor: https://residue.info/c/retatrutide/#kf-pmid-37366315)
- In phase 3 TRIUMPH-1 (2,339 adults with obesity, no diabetes), weight fell 17.6%, 23.7% and 25.0% at the 4, 9 and 12 mg doses versus 3.9% with placebo over 80 weeks; knee-osteoarthritis pain and sleep-apnea events also improved in the nested sub-studies [1]. (anchor: https://residue.info/c/retatrutide/#kf-pmid-42814954)
- In TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes), 80-week weight change was −11.9%, −16.8% and −18.8% versus −5.1% with placebo [2]. (anchor: https://residue.info/c/retatrutide/#kf-pmid-42810372)
- In a 24-week MRI sub-study of people with fatty liver disease, liver fat fell by 81–82% at the 8 and 12 mg doses, and 79–86% reached normal liver fat (<5%) [4]. (anchor: https://residue.info/c/retatrutide/#kf-pmid-38858523)
- Adverse events were mostly gastrointestinal and dose-related; heart rate rose in a dose-dependent way, peaking at 24 weeks [3]. In TRIUMPH-2, hypotension and dysesthesia were also more frequent than with placebo [2]. (anchor: https://residue.info/c/retatrutide/#kf-pmid-37366315-2)

## Effects by system
- Body weight (grade B): Dose-dependent weight reduction of up to −25.0% at 80 weeks in phase 3 [1]. (anchor: https://residue.info/c/retatrutide/#effect-body-weight)
- Glycemic control (grade B): HbA1c fell by 1.69–1.94 percentage points versus 0.81 with placebo at 40 weeks as monotherapy in type 2 diabetes [5]. (anchor: https://residue.info/c/retatrutide/#effect-glycemic-control)
- Liver (grade B): Relative liver-fat reduction of −81.4% (8 mg) and −82.4% (12 mg) at 24 weeks versus +0.3% placebo [4]. (anchor: https://residue.info/c/retatrutide/#effect-liver)
- Musculoskeletal (grade B): Knee-osteoarthritis WOMAC pain improved more than placebo in the TRIUMPH-1 sub-study [1]. (anchor: https://residue.info/c/retatrutide/#effect-musculoskeletal)
- Respiratory / sleep (grade B): Apnea–hypopnea index fell more than placebo in participants with obstructive sleep apnea [1]. (anchor: https://residue.info/c/retatrutide/#effect-respiratory-sleep)
- Cardiovascular (grade B): Dose-dependent heart-rate increase, peaking at 24 weeks [3]; hypotension more frequent than placebo in TRIUMPH-2 [2]. (anchor: https://residue.info/c/retatrutide/#effect-cardiovascular)

## How does Retatrutide work?

Retatrutide is described by its developers' trial reports as a single peptide with agonist activity at three receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor [6]. The first two are the targets of tirzepatide; glucagon-receptor agonism is the addition. Glucagon signaling is studied for its effects on energy expenditure and hepatic fat handling, which is one reason the program includes a dedicated liver-fat sub-study [4].

In the phase 2 liver sub-study, reductions in liver fat tracked changes in body weight, abdominal fat and markers of insulin sensitivity and lipid metabolism [4]. Whether the glucagon component adds benefit beyond weight loss itself has not been isolated in a published trial.

## How long does it last, and how was it scheduled in trials?

Trials administer retatrutide once weekly by subcutaneous injection [1]. Phase 2 work found that gastrointestinal side effects were partially mitigated by starting at 2 mg rather than 4 mg, which is why later protocols escalate the dose stepwise [3]. We have not found a peer-reviewed human half-life value in the records we fetched, so none is given here.

## What did the clinical trials find?

**Obesity without diabetes.** The phase 2 trial randomized 338 adults to 1–12 mg or placebo for 48 weeks. At 24 weeks, the 12 mg group's mean weight change was −17.5% versus −1.6% with placebo; at 48 weeks, it was −24.2% versus −2.1%. At 48 weeks, 83% of the 12 mg group had lost at least 15% of body weight, compared with 2% on placebo [3]. The phase 3 TRIUMPH-1 trial then enrolled 2,339 adults and reported −23.7% (9 mg) and −25.0% (12 mg) at 80 weeks against −3.9% with placebo [1].

**Type 2 diabetes.** In the phase 2 diabetes trial (281 participants across 42 US centers), HbA1c fell by up to 2.02 percentage points at 24 weeks with the 12 mg escalation arm, versus −1.41 with the active comparator dulaglutide 1.5 mg [6]. Phase 3 TRANSCEND-T2D-1 (537 participants) reported HbA1c reductions of 1.69–1.94 points against 0.81 with placebo at 40 weeks, with body-weight reductions of 11.5–15.3% [5]. TRIUMPH-2, in 1,152 people with both obesity and type 2 diabetes, reported up to −18.8% weight change at 80 weeks [2].

**Body composition.** A DXA sub-study of the phase 2 diabetes trial measured total fat mass by DXA at 36 weeks: it fell 26.1% with the pooled 8 mg groups and 23.2% with 12 mg, versus 4.5% with placebo and 2.6% with dulaglutide. The investigators reported that the proportion of lean mass lost relative to total weight lost was similar to other obesity treatments [7].

**The design of the phase 3 program.** TRIUMPH uses a "basket" design: obstructive sleep apnea and knee-osteoarthritis protocols are nested inside the weight-management trials, with a separate cardiovascular-disease population (TRIUMPH-3) and a stand-alone osteoarthritis trial (TRIUMPH-4), totaling more than 5,800 participants [8].

## What adverse events were reported in trials?

Across trials the dominant adverse events were gastrointestinal. In TRIUMPH-2, diarrhea occurred in 27–34% of retatrutide participants versus 13% on placebo, and nausea in 14–28% versus 8% [2]. The same trial reported hypotension in up to 6% and dysesthesia (abnormal skin sensation) in up to 7% of retatrutide participants, versus under 1% and 1% on placebo. Permanent discontinuation due to adverse events or death was 12% at 9 mg and 8% at 12 mg, compared with 5% on placebo; the investigators judged all deaths unrelated to the study drug [2].

In TRANSCEND-T2D-1, discontinuation due to adverse events was 2–5% with retatrutide and 0% with placebo, and no severe hypoglycemia was reported [5]. A dose-dependent rise in heart rate that peaked at 24 weeks and declined thereafter was reported in the phase 2 obesity trial [3].

Retatrutide is not an FDA-approved drug and is not one of the bulk substances FDA lists in its compounding categories. Products sold online as "retatrutide" are outside any approved supply chain; nothing on this page should be read as a description of those products.

## What is still unknown?

- **Long-term outcomes.** Published phase 3 trials run 40–80 weeks; cardiovascular outcomes are being studied in a separate population [8].
- **Heart rate and blood pressure.** The heart-rate rise and the hypotension signal deserve longer follow-up [3][2].
- **Head-to-head data.** No published trial compares retatrutide directly with tirzepatide or semaglutide.

## Frequently asked questions
**Is retatrutide FDA-approved?**
No. At our last data fetch, the openFDA Drugs@FDA database returned no application for retatrutide. It remains investigational, with several phase 3 trials still active on ClinicalTrials.gov [9].

**How much weight did people lose on retatrutide in trials?**
In phase 3 TRIUMPH-1, mean weight change at 80 weeks was −17.6% (4 mg), −23.7% (9 mg) and −25.0% (12 mg) versus −3.9% with placebo in adults with obesity without diabetes [1]. People with type 2 diabetes lost less: up to −18.8% in TRIUMPH-2 [2].

**What are the side effects of retatrutide?**
Trials reported mainly gastrointestinal effects — diarrhea and nausea were the most frequent — that were dose-related and mostly mild to moderate [3][2]. Heart rate increased with dose [3], and hypotension and dysesthesia were more common than with placebo in TRIUMPH-2 [2].

**How is retatrutide different from tirzepatide?**
Tirzepatide activates two receptors (GIP and GLP-1); retatrutide adds a third, the glucagon receptor [3]. No published trial has compared them head to head, so differences in effect size come from separate trials with different populations. See our retatrutide vs tirzepatide comparison.

**What doses of retatrutide were used in trials?**
Phase 3 trials randomized participants to once-weekly 4 mg, 9 mg or 12 mg [1][2]; the phase 2 obesity trial tested 1 to 12 mg [3]. These are trial protocol doses, not recommendations.

**What is retatrutide?**
Retatrutide (LY3437943) is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. It is not FDA-approved; phase 3 TRIUMPH-1 reported mean weight loss of 23.7–25.0% at 80 weeks [1].


## Sources
[1] 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/
[2] 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/
[3] 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/
[4] 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/
[5] Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Bajaj HS et al. Lancet. 2026. https://pubmed.ncbi.nlm.nih.gov/42250575/
[6] Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Rosenstock J et al. Lancet. 2023. https://pubmed.ncbi.nlm.nih.gov/37385280/
[7] Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Coskun T et al. Lancet Diabetes Endocrinol. 2025. https://pubmed.ncbi.nlm.nih.gov/40609566/
[8] Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Giblin K et al. Diabetes Obes Metab. 2026. https://pubmed.ncbi.nlm.nih.gov/41090431/
[9] ClinicalTrials.gov registry search: retatrutide OR LY3437943. 34 registered studies at fetch. https://clinicaltrials.gov/search?intr=retatrutide%20OR%20LY3437943

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