Biologic
RCSB PDB 7KI0
Semaglutide
Ozempic / Wegovy / Rybelsus
- Mechanism of action
- GLP-1 receptor agonist (peptide analog)
- In plain language
- A lab-made copy of a gut hormone that attaches to its natural receptor, prompting the pancreas to release insulin, slowing digestion, and signaling the brain to reduce hunger and food intake.
- How it works
- Semaglutide is a synthetic analog of human GLP-1 with 94% sequence homology to the native hormone, chemically modified with a fatty-diacid side chain that promotes albumin binding and extends its plasma half-life to roughly one week. It selectively binds to and activates the GLP-1 receptor, stimulating glucose-dependent insulin secretion from pancreatic beta cells while suppressing glucagon release, which lowers blood glucose with a low risk of hypoglycemia. It also acts on GLP-1 receptors in brain regions that regulate appetite and produces a minor delay in gastric emptying, both of which increase satiety and reduce caloric intake. This combination of glucose-dependent glycemic effects and central appetite suppression underlies its efficacy in both diabetes management and weight reduction. As Rybelsus, the same molecule is delivered as an oral tablet co-formulated with the absorption enhancer SNAC (salcaprozate sodium), which locally raises gastric pH around the dissolving tablet to protect the peptide from degradation while transiently increasing gastric epithelial permeability — letting a small fraction of intact semaglutide cross into circulation before a peptide, which would otherwise be destroyed by stomach acid and enzymes, is broken down.
- Therapeutic applications
- As Ozempic, semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, to reduce the risk of major adverse cardiovascular events (CV death, non-fatal MI, non-fatal stroke) in adults with type 2 diabetes and established cardiovascular disease, and to reduce the risk of sustained eGFR decline, kidney failure, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. As Wegovy, the same molecule at a higher maintenance dose is indicated, together with a reduced-calorie diet and increased physical activity, for chronic weight management in adults and adolescents (12+) with obesity, or in overweight adults with at least one weight-related comorbid condition, and for reducing cardiovascular risk in adults with established cardiovascular disease and obesity or overweight. As Rybelsus — the oral tablet, marketed under that name outside the US and increasingly as "Ozempic tablets" within the US since 2026 — it carries the same glycemic-control and cardiovascular-risk-reduction indications as injectable Ozempic, but no weight-management indication; because its absorption depends on an intact local pH effect at the tablet surface, it must be taken on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before food, drink, or other oral medications. A separate 25 mg oral tablet marketed as Wegovy was approved in December 2025 specifically for chronic weight management and cardiovascular risk reduction in adults with obesity or overweight.
- Class
- Peptide analog
- Therapeutic area
- Metabolic / Diabetes / Weight Management
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