Overview
Semaglutide selectively activates the GLP-1 receptor: glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying, reduced caloric intake. Half-life ~7 days.
Questions readers ask
What does semaglutide actually do in the body?
Semaglutide activates the GLP-1 receptor, which triggers glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces caloric intake. Together these effects lower blood sugar and appetite.
How is oral semaglutide absorbed if it is a peptide?
Oral semaglutide (Rybelsus) uses an absorption enhancer called SNAC, which allows daily dosing by mouth. That is why it must be taken on an empty stomach with only a small amount of water.
How is semaglutide’s mechanism different from tirzepatide’s?
Semaglutide acts only on the GLP-1 receptor, while tirzepatide is a dual GLP-1/GIP receptor agonist. In SURPASS-2, tirzepatide 15 mg produced −11.2 kg versus −5.7 kg on semaglutide 1 mg at 40 weeks in type 2 diabetes.
Primary sources
- FDA: Concerns with unapproved GLP-1 drugs used for weight loss (current as of October 1, 2026)
- FDA: Policies for compounders as GLP-1 supply stabilizes (updated April 1, 2026)
- FDA: Compounding and the FDA — questions and answers
- FDA: Registered outsourcing facilities (503B)
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med 2021
- Wegovy (semaglutide) prescribing information, Novo Nordisk