Medical Glossary

Semaglutide

weight-loss

Quick Definition

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy). It is administered as a once-weekly subcutaneous injection or as a daily oral tablet, and acts by slowing gastric emptying, increasing satiety signaling, and improving glucose-dependent insulin secretion.

In Depth

Semaglutide was first FDA-approved in 2017 for type 2 diabetes under the brand name Ozempic. The same molecule received approval at higher doses in 2021 for chronic weight management as Wegovy. The oral tablet form, Rybelsus, was approved for type 2 diabetes in 2019.

The molecule binds to and activates the GLP-1 receptor — a receptor normally activated by the body's own GLP-1 hormone after meals. Activation slows gastric emptying (food stays in the stomach longer, producing prolonged fullness), enhances glucose-dependent insulin release (raising insulin only when blood glucose is elevated), and modulates appetite signaling at the hypothalamus.

Semaglutide is engineered for an extended half-life through structural modifications to the native GLP-1 backbone, including a fatty acid chain that allows reversible albumin binding. The result is a half-life of approximately 7 days, supporting once-weekly subcutaneous dosing.

The pivotal weight loss evidence comes from the STEP trial program, which demonstrated approximately 15% mean body weight reduction over 68 weeks in adults with obesity. The diabetes evidence comes from the SUSTAIN trials, which showed both glycemic control and cardiovascular benefit in patients with type 2 diabetes.

Common side effects are concentrated during the dose-titration period and include nausea, diarrhea, vomiting, and constipation. Rare but serious risks include pancreatitis, gallbladder disease, and a labeled warning regarding rodent thyroid C-cell tumors (with contraindication in personal or family history of medullary thyroid carcinoma or MEN2).

Semaglutide is also available through 503A compounding pharmacies in some clinical contexts. The compounded preparations use the same active molecule but are not FDA-approved as finished drug products. The regulatory landscape for compounded semaglutide changed substantially in 2025 following the FDA's resolution of the semaglutide shortage.

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