Semaglutide

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)