Retatrutide
An investigational triple agonist (GIP/GLP-1/glucagon) that produced 24% weight loss in Phase II trials, potentially the most effective obesity drug.
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What is Retatrutide?
Retatrutide is an investigational triple hormone receptor agonist targeting GIP, GLP-1, and glucagon receptors simultaneously. In Phase II trials, it produced up to 24.2% weight loss at 48 weeks — the highest ever recorded for an anti-obesity medication. It is being developed by Eli Lilly with Phase III trials underway.
Why People Talk About It
Record-setting weight loss potential (24%+)
EmergingTriple receptor mechanism (first-in-class)
EmergingPotential NASH/MASH treatment
EmergingHow It Works
Retatrutide activates three hormone receptors at once: GLP-1 and GIP reduce appetite, while glucagon tells your body to burn more energy and fat. This three-pronged approach produces the most weight loss ever seen in a clinical trial.
Common Questions
Safety Information
Common Side Effects
Cautions
- • Not yet FDA-approved
- • Phase III data still being collected
- • Glucagon component may affect blood sugar differently
- • Long-term safety unknown
What We Don't Know
Phase III cardiovascular outcomes, long-term safety, and optimal dosing are still being determined.
Published Research
30 studiesComparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled Trials
Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials
Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA
Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis
Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis
Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis
Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials
Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis
Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis
Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis
Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials
Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials
Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials
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
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
Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study
LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial
Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
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
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice
The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities
Retatrutide in type 2 diabetes mellitus and obesity: an overview
Retatrutide-A Game Changer in Obesity Pharmacotherapy
Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis
The power of three: Retatrutide's role in modern obesity and diabetes therapy
A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity
Retatrutide showing promise in obesity (and type 2 diabetes)
Always consult a qualified clinician
This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician
Research Insights
Related Peptides
Tirzepatide
StrongBeginnerA dual GIP/GLP-1 receptor agonist FDA-approved for diabetes and weight management, producing the largest weight loss seen in clinical trials.
Semaglutide
StrongBeginnerA GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management, one of the most widely prescribed peptide drugs.
Glucagon
StrongBeginnerA naturally occurring peptide hormone that raises blood sugar, FDA-approved as emergency treatment for severe hypoglycemia.
Quick Facts
- Class
- Triple GIP/GLP-1/Glucagon Receptor Agonist
- Evidence
- Emerging
- Safety
- Moderate Data
- Updated
- Mar 2026
- Citations
- 30PubMed
Also known as
Tags
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.
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