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Research · Medication

Retatrutide

Grey marketNot approved for human use in the US, and sold anyway.

In the phase 3 TRIUMPH-1 trial, weekly retatrutide cut body weight 17.6 to 25.0% over 80 weeks, depending on dose, against 3.9% on placebo. In type 2 diabetes, weight fell 11.9 to 18.8% and HbA1c fell up to 1.12 points over placebo. Gastrointestinal events were most common, and hypotension and dysesthesia rose. It is not approved.

Add to Bio HackChecked 2026-11-09
Status
Investigational in the US. Not FDA-approved for any use. In phase 3 trials for obesity, type 2 diabetes and related conditions.
Also called
LY3437943, reta, triple agonist, GIP/GLP-1/glucagon receptor agonist, triple hormone receptor agonist
Taken for
weight loss, fat loss, blood sugar, sleep apnea, knee pain, liver fat

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help7

Reported risks5

What people take it for, and what was found

Shown to help7

Strong

Weight loss in obesity without diabetes

Shown to lower body weight by up to 25% at 80 weeks in adults with obesity without diabetes, against about 4% on placebo.

The numbers and sources
Effect
At 80 weeks, body weight changed by -17.6% on 4 mg, -23.7% on 9 mg and -25.0% on 12 mg, against -3.9% on placebo. Differences from placebo were -19.8 and -21.0 percentage points for 9 mg and 12 mg [1]. In the phase 2 trial, weight changed by -8.7% on 1 mg, -17.1% on 4 mg, -22.8% on 8 mg and -24.2% on 12 mg at 48 weeks, against -2.1% on placebo [2]. Pooling 3 RCTs, weight fell 14.33% more than on placebo [3]. A network meta-analysis found mean weight loss of 11.0 kg on retatrutide, equal to the dual agonists and more than the GLP-1 receptor agonists (9.0 kg). The odds of losing 15% or more were 54.6 on retatrutide [4].
Population
2,339 adults with obesity without diabetes in TRIUMPH-1 [1]; 338 adults with a BMI of 30 or more, or 27 or more with a weight-related condition, 51.8% men [2]; 3 RCTs with 878 adults with obesity, with or without diabetes [3]; 19 RCTs with 29,506 adults with a BMI of 25 or more, comparing six drugs and placebo [4].
Sources
[1], [2], [3], [4]
Caveats
Both trials were funded by Eli Lilly, the developer [1][2]. The sourced trials ran up to 80 weeks. The two meta-analyses searched before the phase 3 results were published, so they pooled phase 2 trials, including people with diabetes [3][4].
Moderate

Weight loss in type 2 diabetes

Shown to lower body weight by about 12% to 19% at 80 weeks in adults with type 2 diabetes, against about 5% on placebo.

The numbers and sources
Effect
At 80 weeks, body weight changed by -11.9% on 4 mg, -16.8% on 9 mg and -18.8% on 12 mg, against -5.1% on placebo, differences of -6.9, -11.8 and -13.8 points [5]. In a 40-week trial without other glucose-lowering drugs, weight changed by -11.5%, -13.9% and -15.3%, against -2.6% on placebo [6].
Population
1,152 adults with type 2 diabetes and a BMI of 27 or more, mean age 55.1, mean BMI 38.2 [5]; 537 adults with type 2 diabetes managed by diet and exercise, mean BMI 35.8 [6].
Sources
[5], [6]
Caveats
Weight loss in these trials was smaller than in TRIUMPH-1, which excluded people with diabetes [1]. Both trials were funded by Eli Lilly [5][6].
Moderate

Blood sugar in type 2 diabetes

Shown to lower HbA1c about 0.9 to 1.1 points more than placebo in adults with type 2 diabetes, with no severe low blood sugar reported.

The numbers and sources
Effect
At 40 weeks, HbA1c changed by -1.69% on 4 mg, -1.86% on 9 mg and -1.94% on 12 mg, against -0.81% on placebo. Differences from placebo were -0.88 (95% CI -1.18 to -0.59), -1.04 (95% CI -1.32 to -0.76) and -1.12 (95% CI -1.39 to -0.85) points. No severe hypoglycemia was reported [6]. A meta-analysis of 8 studies found HbA1c fell 1.04% (95% CI -1.42 to -0.67). Doses of 8 mg or less lowered it more (-1.39%) than doses of 12 mg or more (-0.65%) [7]. Pooling 3 RCTs in adults with obesity, with or without diabetes, HbA1c fell 0.91% more than on placebo [3].
Population
537 adults with type 2 diabetes, baseline HbA1c 7.9%, mean diabetes duration 2.5 years [6]; 8 studies in people with diabetes, obesity or both, framed around chronic kidney disease [7]; 3 RCTs with 878 adults [3].
Sources
[6], [7], [3]
Caveats
The 40-week trial tested retatrutide as a single drug rather than added to others [6]. The abstract of [7] does not say how many participants had kidney disease. [3] mixed people with and without diabetes.
Moderate

Obstructive sleep apnea

Shown to cut sleep apnea events by about 13 to 25 per hour more than placebo in adults with obesity, with smaller drops in those with type 2 diabetes.

The numbers and sources
Effect
At 80 weeks, in people without diabetes, the apnea-hypopnea index fell by 13.2 (4 mg), 24.7 (9 mg) and 22.5 (12 mg) events per hour more than placebo by intention to treat. In people with type 2 diabetes the differences were 8.8, 13.9 and 15.0 events per hour [8].
Population
243 adults without diabetes (baseline 58.6 events per hour) and 448 with type 2 diabetes (55.9 events per hour), with moderate to severe sleep apnea and BMI of 27 or more [8].
Sources
[8]
Caveats
Two trials nested inside the larger weight trials, both funded by Eli Lilly [8].
Limited

Body fat

One trial found fat mass fell up to 26% over 36 weeks in adults with type 2 diabetes, against about 5% on placebo.

The numbers and sources
Effect
At 36 weeks, total fat mass on DXA fell 4.9% on 0.5 mg, 15.2% on 4 mg, 26.1% on 8 mg and 23.2% on 12 mg, against 4.5% on placebo and 2.6% on dulaglutide. Differences from placebo were -0.4 (95% CI -4.0 to 3.2), -10.7 (95% CI -17.2 to -4.2), -21.6 (95% CI -27.1 to -16.1) and -18.7 (95% CI -25.1 to -12.3) points. The authors report the share of weight lost as lean mass was similar to other obesity treatments [9].
Population
189 adults with type 2 diabetes in a substudy of a phase 2 trial, 103 of them with scans at baseline and week 36 [9].
Sources
[9]
Caveats
A substudy of one phase 2 trial. The analysis used participants with scans before stopping the drug. Funded by Eli Lilly [9].
Limited

Knee osteoarthritis pain

One trial found knee pain scores fell about 1.5 points more than placebo in people with knee osteoarthritis. The placebo group also improved.

The numbers and sources
Effect
In people with knee osteoarthritis, the WOMAC pain score changed by -3.4, -3.9 and -4.1 on 4, 9 and 12 mg, against -2.5 on placebo by intention to treat, differences of -1.4 and -1.6 points for 9 mg and 12 mg [1].
Population
574 participants with knee osteoarthritis within TRIUMPH-1 [1].
Sources
[1]
Caveats
A subgroup of one trial. The placebo group also improved by 2.5 points.
Limited

Liver fat

One small trial found liver fat fell up to 82% over 24 weeks in adults with fatty liver disease. Liver scarring and outcomes were not measured.

The numbers and sources
Effect
At 24 weeks, liver fat changed by -42.9% on 1 mg, -57.0% on 4 mg, -81.4% on 8 mg and -82.4% on 12 mg, against +0.3% on placebo. Normal liver fat (under 5%) was reached by 86% on 12 mg and 0% on placebo [10].
Population
98 adults with metabolic dysfunction-associated steatotic liver disease and at least 10% liver fat, a substudy of the phase 2 trial [10].
Sources
[10]
Caveats
A small phase 2 substudy. It measured liver fat, not liver scarring or outcomes.

Risks

Reported risks4

ModerateVery common

Gastrointestinal effects

Shown to raise diarrhea and nausea, the most common side effects, more at higher doses. In diabetes, diarrhea reached 34% against 13% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Gastrointestinal events were the most common adverse events in every trial [1][2][5][6]. In people with diabetes, diarrhea occurred in 27%, 34% and 34% on 4, 9 and 12 mg against 13% on placebo, and nausea in 14%, 21% and 28% against 8% [5]. In phase 2 these events were dose-related and mostly mild to moderate [2].
Population
Trial participants in [1], [2], [5] and [6].
Sources
[1], [2], [5], [6]
Caveats
TRANSCEND-T2D-1 reports the events as subsiding over time [6].
LimitedCommon

Low blood pressure and skin sensation changes

One trial found low blood pressure in up to 6% and abnormal skin sensation in up to 7%, against 1% or less on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Hypotension occurred in 1%, 5% and 6% on 4, 9 and 12 mg against under 1% on placebo. Dysesthesia, an abnormal skin sensation, occurred in 4%, 6% and 7% against 1% [5].
Population
1,152 adults with obesity and type 2 diabetes [5].
Sources
[5]
Caveats
One trial reporting these counts.
Why limited
This rests on one trial, of 1,152 people. Strength counts independent studies that agree, so one trial is limited at any size.
ModerateHow often is not known

Stopping treatment because of adverse events

More people stopped for side effects at some doses: 4% to 12% against 5% on placebo in one trial, and 2% to 5% against 0% in another.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In TRIUMPH-2, permanent discontinuation for adverse events or death was 4% on 4 mg, 12% on 9 mg and 8% on 12 mg, against 5% on placebo. Six people died on retatrutide and one on placebo; investigators judged all deaths unrelated to the drug [5]. In TRANSCEND-T2D-1, discontinuation for adverse events was 2 to 5% on retatrutide and 0% on placebo [6].
Population
1,152 adults [5]; 537 adults [6].
Sources
[5], [6]
Caveats
Death counts are small, and causality was judged by the investigators.
LimitedHow often is not known

Heart rate

One trial found heart rate rose with dose, peaking at 24 weeks and declining after. The size of the rise was not reported.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Heart rate rose in a dose-dependent way, peaking at 24 weeks and declining after that [2].
Population
338 adults in the phase 2 trial [2].
Sources
[2]
Caveats
The abstract gives no size for the rise.

Mixed results1

ModerateHow often is not known

Adverse events overall

Mixed results: one review found adverse events no more common than on placebo, and another ranked retatrutide highest for adverse event risk among obesity drugs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Pooling 3 RCTs, adverse events overall did not differ from placebo (RR 1.11, P 0.24) [3]. In a network meta-analysis of GLP-1 receptor agonists, dual agonists and retatrutide, retatrutide had the highest adverse event risk [4].
Population
3 RCTs with 878 adults [3]; 19 RCTs with 29,506 adults [4].
Sources
[3], [4]
Caveats
The two reviews disagree. [3] compared retatrutide with placebo only. [4] ranked drugs against each other. Both pooled phase 2 trials.

Sources

  1. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. New England Journal of Medicine. 2026. https://doi.org/10.1056/nejmoa2604169
  2. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine. 2023. https://doi.org/10.1056/NEJMoa2301972
  3. Abdrabou Abouelmagd A, Abdelrehim AM, Bashir MN, et al. Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials. Proceedings (Baylor University Medical Center). 2025. https://doi.org/10.1080/08998280.2025.2456441
  4. Sinha B, Ghosal S. Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. Obesity. 2025. https://doi.org/10.1002/oby.24360
  5. Bellido V, le Roux CW, Ekinci EI, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. The Lancet. 2026. https://doi.org/10.1016/s0140-6736(26)01861-1
  6. Bajaj HS, Welch M, Shah P, et al. 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. The Lancet. 2026. https://doi.org/10.1016/s0140-6736(26)00967-0
  7. Pallavi K, Chandra A, Kumar K, et al. Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis. Maedica. 2025. https://doi.org/10.26574/maedica.2025.20.4.824
  8. Grunstein RR, Somers VK, Azarbarzin A, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. New England Journal of Medicine. 2026. https://doi.org/10.1056/nejmoa2611477
  9. Coskun T, Wu Q, Schloot NC, et al. 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. The Lancet Diabetes & Endocrinology. 2025. https://doi.org/10.1016/s2213-8587(25)00092-0
  10. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024. https://doi.org/10.1038/s41591-024-03018-2

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