Retatrutide
An investigational triple GLP-1 / GIP / glucagon receptor agonist showing the largest weight-loss effects yet seen in mid-stage trials.
In plain English
Retatrutide is an investigational peptide from Eli Lilly that activates three receptors at once: GLP-1, GIP, and glucagon. In a Phase 2 trial published in 2023, adults with obesity lost an average of 24.2% of body weight on the highest dose over 48 weeks — the largest mean weight loss reported with any non-surgical drug at that timepoint. Retatrutide is not FDA-approved and is still in Phase 3 trials for obesity, type 2 diabetes, MASH (liver disease), and other indications. Cardiovascular outcome data are still being collected.
What it is
Retatrutide is a single synthetic peptide engineered to activate the GLP-1 receptor, the GIP receptor, and the glucagon receptor simultaneously — a 'triple agonist.'
Mechanism (summary)
Combined GLP-1 + GIP activity is similar to tirzepatide and drives appetite and glucose effects. The added glucagon receptor activity may increase basal energy expenditure and contribute to lipolysis in adipose and liver tissue.
Why people research it
- Chronic weight management in obesity
- Type 2 diabetes
- Metabolic dysfunction-associated steatohepatitis (MASH)
- Hypertension related to obesity
Human evidence
Phase 2 trial in adults with obesity (n=338) showed mean weight loss of 24.2% at 12 mg over 48 weeks vs. 2.1% on placebo. Phase 2 trial in T2D showed HbA1c reductions on par with or exceeding tirzepatide. Phase 3 trials are ongoing.
Animal / lab evidence
Rodent and primate work showed that adding glucagon receptor activity to GLP-1/GIP could produce additional weight loss and improvements in liver fat.
Key studies
Each summary explains the design, what was found, and what it doesn't prove.
In a mid-stage trial, adults with obesity lost roughly a quarter of their body weight on the highest dose of retatrutide over about a year.
In adults with type 2 diabetes, retatrutide produced large drops in HbA1c and substantial weight loss in a Phase 2 trial.
In people with fatty liver and obesity, retatrutide dramatically reduced fat in the liver as measured by MRI.
History
Developed by Eli Lilly. Phase 2 obesity results published in NEJM in 2023. Phase 3 TRIUMPH program initiated 2023–2024.
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