GLP-1 Receptor Agonists

A diabetes drug that mimics a gut hormone, slows gastric emptying, and suppresses appetite — but the GI side effects can derail treatment if the patient isn't prepared.

GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, exenatide) mimic the incretin hormone GLP-1, which is normally released from the gut after eating. They stimulate glucose-dependent insulin secretion — meaning they boost insulin only when blood glucose is elevated, so hypoglycemia risk as monotherapy is low. Simultaneously, they suppress glucagon release, slow gastric emptying, and act on hypothalamic satiety centers to reduce appetite. This combination lowers A1C by 1.0–1.8% and promotes meaningful weight loss, making them preferred add-on therapy for type 2 diabetes when metformin alone is insufficient, especially in patients with obesity or established cardiovascular disease. All GLP-1 agonists carry an FDA boxed warning for thyroid C-cell tumors — they are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome. Most formulations are subcutaneous injections given weekly (semaglutide, dulaglutide) or daily (liraglutide); oral semaglutide exists but must be taken on an empty stomach with ≤4 oz plain water, then nothing for 30 minutes. Doses are titrated slowly upward to minimize GI intolerance. Hypoglycemia risk increases when combined with insulin or sulfonylureas.

Key Distinctions

Don't confuse GLP-1 agonists with DPP-4 inhibitors — both work through the incretin system, but GLP-1 agonists are injectable (mostly), cause more weight loss, and have greater A1C reduction. Students often assume these cause hypoglycemia like sulfonylureas; they do not when used alone because insulin release is glucose-dependent. The pancreatitis risk is real — teach the patient to report sudden severe abdominal pain radiating to the back.

Clinical Pearl

Think 'gut mimic': GLP-1 agonists copy what the gut does after a meal — release insulin, quiet glucagon, slow the stomach, and signal fullness. The gut-like side effects (nausea, vomiting) make sense.