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Glucagon-like peptide-1 (GLP-1) receptor agonist

Semaglutide

Approvedaka Ozempic, Wegovy, Rybelsus

Semaglutide is an approved once-weekly injectable (and once-daily oral) GLP-1 therapy for type 2 diabetes and, at higher doses, for chronic weight management. Randomized trials demonstrate meaningful reductions in HbA1c and body weight, and the SELECT trial showed reduced cardiovascular events in people with overweight or obesity and established cardiovascular disease. It is a prescription medicine used under medical supervision.

Mechanism

In plain terms, semaglutide copies a natural gut hormone that signals fullness and helps control blood sugar. Technically, it is a GLP-1 analogue with high homology to human GLP-1 that agonizes the GLP-1 receptor, stimulating glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and acting on appetite-regulating centers to reduce energy intake. Structural modifications extend its half-life to allow once-weekly (injectable) dosing.

Regulatory Status by Region

  • United States (FDA)Approved. Ozempic for type 2 diabetes (2017, cardiovascular risk reduction added 2020); Rybelsus oral for type 2 diabetes (2019); Wegovy for chronic weight management (2021) and cardiovascular risk reduction (2024); oral Wegovy for weight management approved in 2025.
  • Australia (TGA)Registered on the ARTG - Ozempic for type 2 diabetes and Wegovy for weight management, available on prescription.
  • European Union (EMA)Authorized - Ozempic and Rybelsus for type 2 diabetes and Wegovy for weight management.
  • WADANot prohibited. On the WADA Monitoring Program (introduced 2024, continued into 2026); it is tracked but not a banned substance.

Key Studies

  • Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1; Wilding et al.) (N Engl J Med 2021;384:989-1002; DOI 10.1056/NEJMoa2032183; PMID 33567185)
  • Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT; Lincoff et al.) (N Engl J Med 2023;389:2221-2232; DOI 10.1056/NEJMoa2307563; PMID 37952131)
  • Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6; Marso et al.) (N Engl J Med 2016;375:1834-1844; DOI 10.1056/NEJMoa1607141; PMID 27633186)

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