Compound profile
Retatrutide
Also known as LY3437943
Last reviewed October 2026
Educational only. A summary of published research, not medical advice or a recommendation. No doses are listed.
Quick take
An investigational once-weekly “triple agonist” that acts on the GIP, GLP-1 and glucagon receptors.
- Class
- GLP-1 & weight-loss peptides
- Status
- Investigational
- Evidence
- Large human trials
- Half-life
- About 6 days (early trials)
Mechanism fingerprint
What it acts on, and how. Each chip links to that pathway on the map.
Adds glucagon-receptor activity to GIP and GLP-1 effects; glucagon activity is thought to raise energy use and reduce liver fat.
What makes it different
A “triple agonist”: adds glucagon-receptor activity to GIP and GLP-1 effects, aiming to raise energy use. Still in trials.
Compare side by side
Mechanism & pathways
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Agonist
GLP-1 receptor
Receptor for the gut hormone GLP-1, found on insulin-making cells in the pancreas, in the brain and in the gut. Activating it boosts insulin release when blood sugar is high, slows stomach emptying and reduces appetite.
Leads to Insulin receptor & insulin signaling
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Agonist
GIP receptor
Receptor for GIP, the other main “incretin” gut hormone released after meals. It also boosts insulin release when blood sugar is high, and is found in fat tissue and the brain.
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Agonist
Glucagon receptor
Receptor for glucagon, mainly in the liver. Glucagon raises blood sugar, but in weight-loss drugs its receptor is targeted to raise energy use and reduce liver fat, alongside GLP-1 effects.
Evidence overview
Overall: Large human trials
Human studies
Phase 3 trials in obesity (TRIUMPH-1), obesity with type 2 diabetes (TRIUMPH-2) and type 2 diabetes (TRANSCEND-T2D-1) reported large weight loss and lower HbA1c than placebo, after Phase 1 and 2 studies. A heart and kidney outcomes trial (TRIUMPH-Outcomes) is under way.
Animal studies
In obese mice it lowered body weight and improved blood sugar control. The glucagon-receptor activity added extra energy use on top of the lower food intake driven by its GIP and GLP-1 activity.
Cell & mechanistic studies
In cell assays it activates all three receptors, with balanced glucagon- and GLP-1-receptor activity and stronger GIP-receptor activity. In human liver cells it lowered release of ANGPTL3/8, a protein involved in blood lipids, through the glucagon receptor.
Phase 3 trials in thousands of adults with obesity, with or without type 2 diabetes, reported large weight loss and better blood sugar control, building on Phase 1 and 2 studies. A heart and kidney outcomes trial is still running.
Main areas studied
- Obesity
- Type 2 diabetes
- Knee osteoarthritis pain with obesity
- Obstructive sleep apnea with obesity
- Fatty liver disease (MASLD)
- Heart and kidney outcomes (trial under way)
Being developed for obesity and type 2 diabetes, and studied in related conditions such as knee osteoarthritis pain, sleep apnea and fatty liver disease.
Key research
Selected studies, with the main finding in plain language.
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Human
TRIUMPH-1: Phase 3 in adults with obesity
Average weight change over 80 weeks was −25.0% at the highest dose versus −3.9% on placebo. Knee osteoarthritis pain and sleep apnea events also fell in those subgroups.
Jastreboff AM et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med 2026.
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Human
TRIUMPH-2: Phase 3 in obesity with type 2 diabetes
Average weight change over 80 weeks was −18.8% at the highest dose versus −5.1% on placebo. Gastrointestinal side effects were most common; low blood pressure and dysesthesia were more frequent than with placebo.
Bellido V et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2). Lancet 2026.
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Human
TRANSCEND-T2D-1: Phase 3 in type 2 diabetes
Over 40 weeks HbA1c fell by 1.94 percentage points at the highest dose versus 0.81 on placebo, with weight change of −15.3% versus −2.6%.
Bajaj HS et al. Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1). Lancet 2026.
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Human
Phase 2 in obesity
Average weight change over 48 weeks was −24.2% at the highest dose versus −2.1% on placebo. Heart rate rose with dose, peaking at 24 weeks.
Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023.
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Human
Liver fat substudy (Phase 2)
In people with fatty liver disease, liver fat fell by about 81–82% at 24 weeks at the two highest doses, and 86% of those on the highest dose reached normal liver fat.
Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med 2024.
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Animal
Discovery and first studies
Showed the receptor activity profile in cells, weight loss and better blood sugar control in obese mice, and a Phase 1 profile supporting once-weekly use.
Coskun T et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab 2022.
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Cell / mechanistic
Glucagon receptor and blood lipids
In human liver cells, retatrutide and glucagon lowered ANGPTL3/8 release, which a glucagon-receptor blocker prevented; trial participants' ANGPTL3/8 fell alongside triglycerides and LDL cholesterol.
Wen Y et al. Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids. Diabetes Obes Metab 2025.
Side effects & risks
Reported side effects
- Nausea, vomiting, diarrhea and constipation, mostly during the step-up phase of treatment
- Higher heart rate at higher doses
- Dysesthesia (unusual skin sensations such as tingling or burning), more common than with placebo in Phase 3
- Low blood pressure, more common than with placebo in Phase 3
Risks and warnings
- Long-term safety is not yet established
- Products sold as “research use only” are not quality-controlled medicines; purity, sterility and labeled amount are not verified.
FAQ
Short answers taken from this profile.
What is Retatrutide?
An investigational once-weekly “triple agonist” that acts on the GIP, GLP-1 and glucagon receptors.
How does Retatrutide work?
Adds glucagon-receptor activity to GIP and GLP-1 effects; glucagon activity is thought to raise energy use and reduce liver fat.
What receptors or pathways does Retatrutide act on?
GLP-1 receptor (agonist), GIP receptor (agonist) and glucagon receptor (agonist). Downstream, that leads to insulin receptor & insulin signaling.
How is Retatrutide different from similar compounds?
A “triple agonist”: adds glucagon-receptor activity to GIP and GLP-1 effects, aiming to raise energy use. Still in trials.
What is the half-life of Retatrutide?
About 6 days (early trials).
Is Retatrutide approved?
Not approved. Phase 3 trials have reported results, and Eli Lilly has said it plans to apply for FDA approval in early 2027.
What has Retatrutide been studied for?
Obesity, Type 2 diabetes, Knee osteoarthritis pain with obesity, Obstructive sleep apnea with obesity, Fatty liver disease (MASLD) and Heart and kidney outcomes (trial under way). Being developed for obesity and type 2 diabetes, and studied in related conditions such as knee osteoarthritis pain, sleep apnea and fatty liver disease.
How strong is the evidence?
Large human trials. Phase 3 trials in thousands of adults with obesity, with or without type 2 diabetes, reported large weight loss and better blood sugar control, building on Phase 1 and 2 studies. A heart and kidney outcomes trial is still running.
What are the main risks?
Long-term safety is not yet established. Products sold as “research use only” are not quality-controlled medicines; purity, sterility and labeled amount are not verified.
Sources
- Jastreboff AM et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1). N Engl J Med 2026.
- Bellido V et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2). Lancet 2026.
- Bajaj HS et al. Retatrutide in type 2 diabetes (TRANSCEND-T2D-1). Lancet 2026.
- Jastreboff AM et al. Triple–hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023.
- Sanyal AJ et al. Retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med 2024.
- Coskun T et al. LY3437943 from discovery to clinical proof of concept. Cell Metab 2022.
- Wen Y et al. ANGPTL3/8 and serum lipids with retatrutide. Diabetes Obes Metab 2025.