Semaglutide
A GLP-1 receptor agonist FDA-approved for type 2 diabetes (Ozempic) and chronic weight management (Wegovy).
In plain English
Semaglutide is a long-acting analog of GLP-1, a gut hormone released after eating. It lowers blood sugar, slows stomach emptying, and reduces appetite. In large randomized trials — including STEP and SUSTAIN — semaglutide produced average weight loss of roughly 12–15% of body weight over about 68 weeks in people with overweight or obesity, alongside meaningful improvements in HbA1c in people with type 2 diabetes. The SELECT trial also showed reduced major cardiovascular events in people with overweight and pre-existing cardiovascular disease. Semaglutide is FDA-approved as Ozempic and Wegovy and is one of the most-studied peptides ever brought to market.
What it is
Semaglutide is a 31-amino-acid acylated peptide that mimics human GLP-1 with modifications that extend its half-life so it can be dosed weekly.
Mechanism (summary)
Semaglutide activates the GLP-1 receptor in pancreatic islets (boosting glucose-dependent insulin release and suppressing glucagon), the gut (slowing gastric emptying), and the brain (reducing appetite and food reward).
Why people research it
- Type 2 diabetes glycemic control
- Chronic weight management
- Major adverse cardiovascular event reduction in people with overweight and CVD
- Investigational use in MASH (fatty liver) and addiction phenotypes
Human evidence
Tens of thousands of patients across the SUSTAIN, STEP, PIONEER, and SELECT trial programs. Average weight loss in STEP-1 was about 14.9% over 68 weeks in adults with obesity. SELECT showed a 20% relative reduction in major adverse cardiovascular events vs. placebo.
Animal / lab evidence
Rodent and primate studies of GLP-1 agonists support effects on insulin secretion, gastric emptying, and central appetite circuits. C-cell tumors observed in rats led to a boxed warning, though human relevance remains unclear.
Key studies
Each summary explains the design, what was found, and what it doesn't prove.
Adults with overweight or obesity lost an average of about 15% of their body weight on weekly semaglutide over 68 weeks, vs. about 2.4% on placebo.
In a large heart-disease trial, people on semaglutide had 20% fewer major cardiovascular events than people on placebo over about 3 years.
In a head-to-head trial, semaglutide lowered blood sugar and weight more than another GLP-1 drug, liraglutide.
History
Developed by Novo Nordisk. Ozempic was approved for type 2 diabetes in 2017; Wegovy was approved for chronic weight management in 2021; oral semaglutide (Rybelsus) was approved in 2019. SELECT cardiovascular indication added 2024.
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