How is retatrutide different from semaglutide or tirzepatide?

Semaglutide is a single GLP-1 agonist and tirzepatide is a dual GLP-1/GIP agonist, while retatrutide adds a third action at the glucagon receptor. That glucagon component is thought to further raise energy expenditure and fat oxidation, contributing to larger weight loss in trials.

Is retatrutide FDA-approved?

As of the research framing here it is an investigational compound in late-stage clinical trials and not yet approved. All sourced material is for research purposes only.

Why might glucose rise at higher doses?

Glucagon receptor agonism can transiently increase hepatic glucose output, which is why glycemic parameters are monitored carefully during retatrutide dose escalation in studies.

← All peptides

Weight & Metabolic

Clinical

Retatrutide

Also known as: Retatrutide, LY3437943

Retatrutide is an investigational triple agonist that simultaneously activates the GLP-1, GIP, and glucagon receptors, studied for substantial weight loss and improved glycemic control. It is one of the most potent incretin-based agents in late-stage clinical development.

Mechanism of Action

Retatrutide is a synthetic peptide that acts as a balanced agonist at three receptors: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR). GLP-1R and GIPR agonism enhance glucose-dependent insulin secretion, slow gastric emptying, and reduce appetite via hypothalamic and brainstem circuits, while glucagon receptor agonism increases energy expenditure and hepatic lipid mobilization. The added glucagon component is thought to drive greater fat oxidation and metabolic rate compared with dual GLP-1/GIP agonists, producing larger reductions in body weight and hepatic fat in clinical trials.

Half-life: Approximately 6 days, supporting once-weekly dosing
Administration Routes: subcutaneous
Research Status: Clinical

Retatrutide

Also known as: Retatrutide, LY3437943