Ozempic Drug Class
Ozempic (semaglutide) is a GLP-1 receptor agonist (glucagon-like peptide-1 receptor agonist), a class of medications that selectively binds to and activates GLP-1 receptors to lower blood glucose and reduce body weight. 1
Mechanism of Action
Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1, functioning as a receptor agonist that targets the GLP-1 receptor 1. The medication works through multiple physiological mechanisms:
- Glucose-dependent insulin secretion: Stimulates both first- and second-phase insulin release when blood glucose is elevated 1
- Glucagon suppression: Lowers fasting and postprandial glucagon concentrations in a glucose-dependent manner, reducing hepatic glucose production 1
- Delayed gastric emptying: Slows gastric peristalsis while increasing pyloric tone in the early postprandial phase 1
- Appetite suppression: Acts centrally on hypothalamic receptors to reduce food intake 2
The principal mechanism of protraction resulting in semaglutide's long half-life of approximately 1 week is albumin binding, which decreases renal clearance and provides protection from metabolic degradation 1. Additionally, semaglutide is stabilized against degradation by the DPP-4 enzyme 1.
Clinical Classification and Formulations
Semaglutide belongs to the GLP-1 receptor agonist drug class and is available in two formulations 3:
- Subcutaneous injection: Ozempic is administered once weekly at doses of 0.5 mg or 1.0 mg for type 2 diabetes management 3
- Higher-dose subcutaneous: Wegovy (semaglutide 2.4 mg weekly) is approved specifically for chronic weight management 2
- Oral formulation: Rybelsus is the first FDA-approved oral GLP-1 receptor agonist, though it is less potent than injectable formulations 2
Pharmacodynamic Effects
Semaglutide demonstrates robust glucose-lowering effects in patients with type 2 diabetes 1:
- Reduces fasting glucose by 29 mg/dL (22% reduction) compared to placebo 1
- Decreases 2-hour postprandial glucose by 74 mg/dL (36% reduction) 1
- Lowers mean 24-hour glucose concentration by 30 mg/dL (22% reduction) 1
- Reduces fasting glucagon by 8% and postprandial glucagon response by 14-15% 1
Cardiovascular Benefits
Beyond glycemic control, semaglutide has demonstrated significant cardiovascular benefits in clinical trials 3:
- The SUSTAIN-6 trial showed a 26% reduction in the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.74,95% CI 0.58-0.95) 3
- Cardiovascular deaths were reduced by 22% in the semaglutide group compared to placebo (HR 0.78,95% CI 0.66-0.93) 3
- The SELECT trial demonstrated a 20% reduction in major adverse cardiovascular events in patients with obesity and established cardiovascular disease 2
Safety Profile
The most common adverse effects are gastrointestinal, including nausea, vomiting, and diarrhea, which are typically mild-to-moderate and transient 4. Semaglutide carries a contraindication for patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 based on animal studies 2, 1. The medication has been associated with increased risk of pancreatitis and gallbladder disease, though causality has not been definitively established 4.
Renal and Hepatic Considerations
No dose adjustment is required for patients with renal impairment, including end-stage renal disease, as no clinically relevant changes in semaglutide pharmacokinetics were observed 1. Similarly, no dose adjustment is needed for patients with hepatic impairment 1.