Semaglutide : données probantes, mécanisme et limites

Semaglutide is a synthetic peptide that mimics the gut hormone GLP-1. It is modified to bind albumin in the blood and resist breakdown, which gives it a long half-life. It is made by Novo Nordisk.

Semaglutide is sold under three brand names in the United States. The brands differ in form and approved uses, so the label of each product is the reference for what it is approved for.

Semaglutide activates the GLP-1 receptor. In human pharmacology this increases insulin release when blood sugar is high, lowers glucagon, slows stomach emptying and reduces appetite through the brain. These effects are well characterized in people, not only in animals.

The evidence base is large. The STEP 1 randomized trial showed substantial, sustained weight loss compared with placebo in adults with overweight or obesity without type 2 diabetes. The SELECT trial tested cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes. The FLOW trial tested kidney outcomes in people with type 2 diabetes and chronic kidney disease. Novo Nordisk, which makes semaglutide, funded all three trials.

Each finding applies to the population the trial studied, and improvement in one population does not transfer automatically to another. Head-to-head trials against tirzepatide, in type 2 diabetes and in obesity, favored tirzepatide for weight reduction; both were funded by tirzepatide's maker.

All three labels carry a boxed warning: semaglutide caused thyroid C-cell tumors in rodents, and it is unknown whether it causes these tumors, including medullary thyroid carcinoma, in humans. Semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2.

The most common adverse reactions on the Ozempic label are nausea, vomiting, diarrhea, abdominal pain and constipation. The Wegovy label also lists dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, belching, flatulence, gastroenteritis, reflux, hair loss and, in type 2 diabetes, low blood sugar.

The labels' warnings include acute pancreatitis, gallbladder disease, acute kidney injury from fluid loss, severe gastrointestinal reactions, serious allergic reactions, diabetic retinopathy complications, low blood sugar when combined with insulin or insulin secretagogues, and pulmonary aspiration during anesthesia or deep sedation. The Wegovy label adds heart rate increase.

FDA declared the semaglutide injection shortage resolved on February 21, 2025, and the grace periods for compounders have ended. In an update dated April 1, 2026, FDA said semaglutide is on neither its drug shortage list nor the 503B bulks list. FDA also warns that some compounders use salt forms, such as semaglutide sodium or acetate, which are different active ingredients from the approved drug, and it has received reports of counterfeit Ozempic.

Semaglutide is not on the WADA Prohibited List. WADA monitors it in and out of competition under its 2026 Monitoring Program.