Role of Semaglutide (Wegovy) in Weight Management
Semaglutide 2.4 mg weekly is highly effective for weight management in overweight and obese individuals, providing substantial weight loss of 14.9-17.4% at 68 weeks and significant cardiovascular risk reduction of 20% in patients with pre-existing cardiovascular disease. 1
Efficacy for Weight Loss
Semaglutide offers remarkable weight loss benefits compared to other weight management medications:
- Mean weight reduction of 14.9-17.4% in non-diabetic overweight/obese patients at 68 weeks 1
- Lower but still significant weight loss (9.6%) in patients with type 2 diabetes 2
- Long-term effectiveness maintained at 24 months with approximately 20.4% weight loss in real-world settings 3
- 69-79% of patients achieve ≥10% weight loss and 51-64% achieve ≥15% weight loss 2
Cardiovascular Benefits
Beyond weight loss, semaglutide provides significant cardiovascular protection:
- Reduces primary cardiovascular endpoints (cardiovascular death, non-fatal myocardial infarction, or stroke) by 20% in patients with pre-existing cardiovascular disease and BMI ≥27 1
- Provides multiple cardioprotective mechanisms including:
- Anti-inflammatory and anti-atherosclerotic effects
- Improved myocardial substrate utilization
- Reduced myocardial ischemia injury
- Lower systemic and pulmonary vascular resistance
- Improved lipid profiles 1
Mechanism of Action
Semaglutide works through several complementary mechanisms:
- Acts as a GLP-1 receptor agonist with 94% sequence homology to human GLP-1 4
- Stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner 4
- Delays gastric emptying, reducing postprandial glucose appearance 4
- Binds extensively to albumin (>99%), providing a long half-life of approximately 1 week 4
Dosing and Administration
The recommended dosing schedule for semaglutide in weight management:
- Starting dose: 0.25 mg subcutaneously once weekly for weeks 1-4 1
- Titration: 0.5 mg weekly for weeks 5-8 1
- Maintenance dose: 2.4 mg weekly 1
- No dosage adjustments required for patients with renal or hepatic impairment 1, 4
Safety Profile and Adverse Effects
Common adverse effects include:
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 1, 5
- Potential cardiac arrhythmias/tachycardia 1
- Gallbladder disorders 1
Management strategies for adverse effects:
- Start at low dose and titrate slowly
- Reduce meal size
- Limit alcohol and carbonated drinks
- Avoid high-fat diet
- Monitor for gallbladder symptoms 1
Contraindications
Important contraindications to consider:
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2
- Pregnancy
- History of pancreatitis or gallbladder disease (use with caution) 1
Patient Selection
Semaglutide 2.4 mg is indicated for:
- Adults with BMI ≥30 kg/m² 5
- Adults with BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia) 5
- Patients with type 2 diabetes, particularly those with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD 1
- Patients with chronic coronary syndrome who have overweight or obesity 1
Comparison with Other Medications
While semaglutide provides substantial weight loss, tirzepatide may offer better value:
- Tirzepatide provides greater weight loss at higher doses (15 mg: 20.9% at 72 weeks) 1
- Cost needed to treat per 1% of body weight reduction: $985 for tirzepatide vs. $1845 for semaglutide 1
Clinical Considerations
- Semaglutide should be used as an adjunct to reduced-calorie diet and increased physical activity 5
- The WeGoTogether patient support program may enhance real-world effectiveness 3
- Insurance coverage may limit clinical utilization 6
- Long-term use (up to 2 years) has been confirmed as safe and effective 5, 3