GLP-1 (glucagon-like peptide-1)

Glucagon-like peptide-1 is an incretin hormone secreted by cells in the intestine within minutes of a meal. It acts on the GLP-1 receptor in the pancreas to increase insulin release in a glucose-dependent way, suppresses glucagon, slows the emptying of the stomach, and acts on the brain to reduce appetite. Native GLP-1 is cleared in about two minutes by the enzyme DPP-4, which is why it is not useful as a drug in its natural form.

GLP-1 receptor agonists are engineered analogues that resist DPP-4 and bind albumin, extending the half-life from minutes to days. Semaglutide is the most studied single GLP-1 agonist and is approved in Canada under the brand names Ozempic and Wegovy. Tirzepatide combines GLP-1 activity with GIP, and retatrutide adds the glucagon receptor as well.

The class shares a side-effect profile driven by the slowing of gastric emptying: nausea, reduced appetite and gastrointestinal upset are the most common findings in trials, which is why every approved product is titrated up over weeks. The GLP-1 receptor agonists comparison covers the class and each profile covers its compound.