Semaglutide
Semaglutide (GLP-1 receptor agonist)
Also known as: Ozempic, Wegovy, Rybelsus
A long-acting GLP-1 receptor agonist approved for type 2 diabetes and chronic weight management, with proven cardiovascular risk reduction.
Overview
Semaglutide is a once-weekly GLP-1 receptor agonist. It lowers blood glucose through glucose-dependent insulin secretion, slows gastric emptying, and reduces appetite through central and peripheral GLP-1 signaling. It is one of the most extensively studied metabolic compounds of the last decade, with large randomized trials in both diabetes and obesity. Update, September 2026: an oral 25 mg Wegovy pill was approved in December 2025 (13.6% mean weight loss at 64 weeks in OASIS 4, 16.6% among participants who stayed on treatment), and a 7.2 mg injectable dose was approved in March 2026 (18.7% at 72 weeks in STEP UP, 20.7% among those who stayed on treatment, with skin dysesthesia in about 23%). The evoke and evoke+ Phase 3 trials in Alzheimer's disease (3,808 participants) failed their primary endpoint.
Mechanism of action
Activates the GLP-1 receptor, increasing insulin secretion when glucose is elevated, suppressing glucagon, slowing gastric emptying, and acting on hypothalamic appetite centers to reduce food intake.
Key studies & citations
- Human2023
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
17,604 adults with cardiovascular disease and BMI 27 or higher but no diabetes: semaglutide 2.4 mg cut major adverse cardiovascular events 20% (6.5% vs 8.0%; HR 0.80) over a mean 39.8 months.
New England Journal of Medicine - Human2021
Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
1,961 adults without diabetes: mean body weight change of -14.9% at 68 weeks with semaglutide 2.4 mg versus -2.4% with placebo; 86.4% lost 5% or more.
New England Journal of Medicine - Human2026
Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials
3,808 participants with amyloid-confirmed early Alzheimer's disease across 566 sites: oral semaglutide did not slow decline on the CDR-SB primary endpoint at week 104 and both trials were discontinued for negative clinical outcome.
The Lancet - Human2025
Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4)
307 adults randomized 2:1: oral semaglutide 25 mg produced -13.6% body weight at week 64 versus -2.2% with placebo (treatment-policy estimand); GI adverse events in 74.0% vs 42.2%.
New England Journal of Medicine - Human2025
Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial
1,407 adults: -18.7% body weight at 72 weeks on 7.2 mg versus -15.6% on 2.4 mg and -3.9% on placebo; dysaesthesia reported by 22.9% on 7.2 mg.
The Lancet Diabetes & Endocrinology
Frequently asked questions
Is semaglutide FDA-approved?
Yes. It is approved for type 2 diabetes (Ozempic, Rybelsus) and for chronic weight management (Wegovy) in adults meeting BMI criteria.
What is the evidence level for semaglutide?
Strong. It has been studied in multiple large randomized controlled trials for glycemic control, weight loss, and cardiovascular outcomes.