Retatrutide

Triple hormone receptor agonist (GIP/GLP-1/glucagon) · Also known as LY3437943

What is retatrutide?

A next-generation triple agonist peptide that simultaneously activates GIP, GLP-1, and glucagon receptors. In Phase 3 trials, participants lost an average of 28.7% of their body weight at the highest dose, making it one of the most potent weight loss agents ever studied.

Developed by Eli Lilly, retatrutide is a 39-amino-acid peptide linked to a fatty acid chain that extends its half-life to roughly six days, enabling once-weekly dosing. Unlike dual agonists such as tirzepatide, retatrutide adds glucagon receptor activation, which increases energy expenditure and promotes fat burning on top of the appetite-suppressing effects of GLP-1 and GIP. Phase 3 results from the TRIUMPH program demonstrated average weight loss of 71.2 lbs (32.3 kg) at 68 weeks on the 12 mg dose. Retatrutide is not yet FDA-approved and is currently in late-stage clinical trials.

Key takeaway: Retatrutide achieved the highest weight loss of any obesity drug in clinical trials to date, with nearly 29% average body weight reduction at the 12 mg dose.

Benefits & evidence

Weight loss High confidence
Blood sugar control High confidence
Liver fat reduction High confidence
Appetite suppression High confidence
Improved metabolic markers Moderate confidence

How it works

Retatrutide activates three receptors at once. Its GLP-1 receptor activity suppresses appetite and slows gastric emptying, making you feel full longer. GIP receptor activation enhances insulin secretion in a glucose-dependent manner and plays a role in lipid metabolism, helping reduce fat storage.

The third component - glucagon receptor activation - is what sets retatrutide apart from dual agonists. Glucagon promotes hepatic glucose production, thermogenesis, and lipid mobilization, meaning your body actively burns more energy and breaks down stored fat. This three-pronged approach creates synergistic metabolic benefits that exceed what any single or dual agonist can achieve alone.

Dosing information

Typical dosing protocol
Starting dose

2 mg/week

Weeks 1-4
Maintenance dose

9-12 mg/week

After titration period

Dose is escalated in steps (2 mg → 4 mg → 6 mg → 9 mg → 12 mg) every 4 weeks. Not yet FDA-approved; dosing is based on clinical trial protocols.

Side effects

Most side effects tend to improve as your body adjusts.

Nausea Common
Diarrhea Common
Constipation Common
Vomiting Moderate
Dysesthesia (skin tingling) Uncommon
Pancreatitis Rare

Research (10 studies)

Retatrutide in type 2 diabetes mellitus and obesity: an overview. Expert review of clinical pharmacology · 2026