How does Wegovy (semaglutide) work?

How Wegovy (Semaglutide) Works

Wegovy (semaglutide) works primarily as a GLP-1 receptor agonist that mimics the effects of the natural hormone GLP-1, acting on the hypothalamus to suppress appetite, delay gastric emptying, increase glucose-dependent insulin release, decrease glucagon secretion, and increase pancreatic β-cell growth. 1

Mechanism of Action

Semaglutide is a human GLP-1 receptor agonist with 94% sequence homology to human GLP-1. It selectively binds to and activates the GLP-1 receptor, which is the target for native GLP-1 hormone. 2

The key mechanisms through which Wegovy works include:

• Appetite suppression: Acts on the hypothalamus (brain's appetite control center) to reduce hunger and food cravings 1, 3
• Delayed gastric emptying: Slows the rate at which food leaves the stomach, promoting feelings of fullness 2
• Glucose regulation: Stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner 2

Molecular Structure and Pharmacokinetics

Wegovy's effectiveness is enhanced by several structural modifications:

• Albumin binding facilitated by modification at position 26 with a hydrophilic spacer and C18 fatty di-acid
• Stabilization against DPP-4 enzyme degradation through modification at position 8
• These modifications result in a long half-life of approximately 1 week 2

Effects on Weight Management

Wegovy's weight loss effects occur through multiple pathways:

1. Control of eating behaviors: Significantly improves craving control and reduces hunger 4
2. Reduced caloric intake: By suppressing appetite and delaying gastric emptying, patients naturally consume fewer calories 3
3. Improved satiety signals: Enhances feelings of fullness after meals 1

Clinical trials have demonstrated that Wegovy produces substantial weight loss:

• 14.9-16.0% weight loss at 68 weeks with 2.4 mg weekly dosing 1, 3
• Significantly greater weight loss compared to placebo and other anti-obesity medications 5, 6

Cardiovascular and Metabolic Benefits

Beyond weight loss, Wegovy offers additional health benefits:

• Cardiovascular protection: Reduces the risk of cardiovascular death, heart attacks, and strokes by 20% in adults with obesity or overweight and cardiovascular disease 1, 3
• Improved metabolic parameters: Decreases blood pressure and improves cholesterol profiles 1

Important Clinical Considerations

• Long-term therapy: Significant weight regain occurs after discontinuation, highlighting the need for continued treatment 1, 3
• Combination therapy: Most effective when used with lifestyle modifications (reduced-calorie diet and physical activity) 1
• Common side effects: Primarily gastrointestinal symptoms including nausea, vomiting, diarrhea, and constipation 3

Distinguishing Features

Wegovy differs from other GLP-1 receptor agonists like liraglutide by:

• Having a longer half-life (approximately 1 week)
• Requiring only once-weekly administration
• Producing greater weight loss (14.9-16.0% vs. 8.0% with liraglutide) 1, 3, 7

Wegovy represents a significant advancement in obesity pharmacotherapy by targeting multiple physiological pathways involved in weight regulation, with the primary mechanism being GLP-1 receptor activation in the brain's appetite control centers.