Wegovy (Semaglutide 2.4 mg) for Obesity Management
Primary Indication and Eligibility
Wegovy is FDA-approved for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, or dyslipidemia), and must be used as adjunct to reduced-calorie diet and increased physical activity. 1, 2
- Adults with BMI ≥30 kg/m² qualify without additional requirements 1
- Adults with BMI ≥27 kg/m² require at least one weight-related condition such as dyslipidemia, hypertension, or type 2 diabetes 1, 3
- Treatment must be combined with a 500-kcal daily deficit and minimum 150 minutes per week of physical activity 1, 2
Dosing Schedule and Administration
Semaglutide requires slow titration over 16-20 weeks to minimize gastrointestinal adverse effects, which occur in over 50% of patients without gradual dose escalation. 1, 2
Standard Titration Protocol:
- Weeks 1-4: 0.25 mg subcutaneously once weekly 1
- Weeks 5-8: 0.5 mg once weekly 1
- Weeks 9-12: 1.0 mg once weekly 1
- Weeks 13-16: 1.7 mg once weekly 1
- Week 17 onward: 2.4 mg once weekly (maintenance dose) 1
Missed Dose Management:
- If ≤4 days since missed dose: administer as soon as possible 1
- If >4 days since missed dose: skip and resume at next scheduled dose 1
- If ≥3 consecutive doses missed: consider restarting the titration schedule 1
Expected Weight Loss Outcomes
Semaglutide 2.4 mg achieves mean weight loss of 14.9-17.6% at 68 weeks, with 64.9% of patients achieving ≥10% total body weight loss. 1, 2, 4
- At 6 months: mean weight loss of 13.4% 4
- At 12 months: mean weight loss of 17.6%, with 43.3% achieving ≥20% weight loss 4
- At 18-24 months: mean weight loss of 20.3-20.4%, with approximately 50% achieving ≥20% weight loss 4, 5
- Weight loss is typically lower in patients with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 1, 2
Absolute Contraindications
Semaglutide is absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) based on animal studies showing thyroid C-cell tumor formation. 1, 2
- Personal or family history of medullary thyroid cancer 1, 2
- Multiple endocrine neoplasia syndrome type 2 1, 2
- Pregnancy or breastfeeding 1
- History of severe hypersensitivity reaction to semaglutide 1
Common Adverse Effects and Management
Gastrointestinal effects are the most common adverse events, occurring in 53-82% of patients, but are typically mild-to-moderate and transient, decreasing over time with continued exposure. 1, 2
Gastrointestinal Effects:
- Nausea (18-44% of patients) 1, 2
- Diarrhea (12-32%) 1
- Vomiting (8-25%) 1, 2
- Constipation (10-23%) 1
- Abdominal pain 1, 2
Mitigation Strategies:
- Slow titration over 16-20 weeks 1, 2
- Reduce meal size and eat slowly 1
- Limit alcohol and carbonated beverages 1
- Most symptoms resolve within 4-8 weeks 1
Serious Adverse Events:
- Pancreatitis: Monitor for persistent severe abdominal pain; discontinue if suspected 1, 2
- Gallbladder disease: 38% higher risk of cholelithiasis and cholecystitis versus placebo; avoid in patients with symptomatic gallstones 1, 2
- Delayed gastric emptying: Creates aspiration risk during anesthesia; discontinue at least 3 weeks before elective surgery 1
Monitoring Recommendations
Patients should be assessed every 4 weeks during dose titration, then every 3 months after reaching maintenance dose to evaluate weight loss progress, cardiovascular risk factors, and adverse effects. 1
During Titration (Weeks 0-16):
- Assess every 4 weeks for gastrointestinal tolerance 1
- Monitor weight loss progress 1
- Check blood pressure (may decrease with weight loss, requiring antihypertensive adjustment) 1
- Evaluate for signs of pancreatitis or gallbladder disease 1
After Reaching Maintenance Dose:
- Assess at least every 3 months for weight stability, cardiovascular risk factors, and medication adherence 1
- Evaluate treatment response at 12-16 weeks on maximum tolerated dose 1
- Discontinue if <5% weight loss after 3 months at therapeutic dose 1, 2
Special Monitoring:
- Blood pressure monitoring (may require antihypertensive adjustment) 1
- Signs of pancreatitis (persistent severe abdominal pain) 1
- Signs of gallbladder disease (right upper quadrant pain) 1
- Nutritional status 1
Cardiovascular Benefits
Semaglutide 2.4 mg provides a 20% reduction in cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with established cardiovascular disease and BMI ≥27, even without diabetes. 1, 2
- Proven cardiovascular benefit in the SELECT trial (HR 0.80,95% CI 0.72-0.90) 1
- Reduces blood pressure, lipid profiles, and inflammatory markers 1
- Improves heart failure symptoms in patients with HFpEF (13.7-point improvement in Kansas City Cardiomyopathy Questionnaire versus 6.4 points with placebo) 1
- Prioritize semaglutide 2.4 mg for patients with established cardiovascular disease requiring proven cardiovascular benefit 1
Renal Considerations
No dose adjustment is required for semaglutide across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m², making it a preferred option in advanced CKD. 1
- Reduces albuminuria by 20.6% at 68 weeks 1
- Slows eGFR decline 1
- Monitor for dehydration secondary to gastrointestinal side effects in patients with renal impairment 1
Concomitant Medication Adjustments
When initiating semaglutide in patients on insulin or sulfonylureas, reduce insulin by 20% and discontinue or reduce sulfonylurea doses by 50% to prevent hypoglycemia. 1
- Reduce basal insulin by approximately 20% 1
- Discontinue or reduce sulfonylurea doses by 50% 1
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 1
- Semaglutide has minimal intrinsic hypoglycemia risk when used as monotherapy 1
Long-Term Use and Weight Maintenance
Semaglutide must be used lifelong for sustained weight loss, as discontinuation results in regain of one-half to two-thirds of lost weight within 1 year. 1, 2, 6
- After cessation, significant weight regain occurs (6.9-11.6% of lost weight regained after 52 weeks) 1, 2
- Continued treatment with semaglutide resulted in additional 7.9% weight loss versus 6.9% weight regain with placebo over 48 weeks 6
- Patients should be counseled that lifelong treatment is typically necessary to maintain weight loss and metabolic benefits 1
Alternative Pharmacologic Options
Tirzepatide 15 mg weekly demonstrates superior weight loss (20.9% at 72 weeks) compared to semaglutide 2.4 mg (14.9%), but semaglutide remains the preferred choice for patients with established cardiovascular disease due to proven cardiovascular outcome benefits. 1
Tirzepatide (Zepbound/Mounjaro):
- Superior weight loss: 20.9% at 72 weeks versus 14.9% with semaglutide 1
- Dual GIP/GLP-1 receptor agonist 1
- Greater waist circumference reduction and superior triglyceride reduction 1
- FDA-approved starting dose: 5 mg weekly, titrated to maximum 15 mg weekly 1
- Cost: approximately $1,272 per 30-day supply 1
Liraglutide 3.0 mg (Saxenda):
- Mean weight loss of 5.24-6.1% 1
- Daily subcutaneous injection 1
- Consider when weekly injections are not tolerated or refused 1
- Cost: approximately $1,619 per 30-day supply 1
Oral Semaglutide (Rybelsus):
- Less potent than injectable formulations for weight management 1
- FDA-approved only for type 2 diabetes treatment, not obesity management 1
- HbA1c reductions of approximately 1.4% from baseline 1
- Consider when patient strongly prefers to avoid injections and glycemic control is the primary goal 1
Cost Considerations
Semaglutide 2.4 mg costs approximately $1,557-$1,619 per 30-day supply, requiring long-term financial planning and insurance authorization. 1
- Average wholesale price: $1,557-$1,619 per 30-day supply 1
- Insurance authorization may be challenging, particularly for obesity management without diabetes 1
- Payors should cover evidence-based obesity treatments to reduce barriers to treatment access 1
Common Pitfalls to Avoid
- Do not initiate at maintenance dose (2.4 mg): Markedly raises gastrointestinal adverse events and discontinuation rates; slow titration over 16-20 weeks is essential 1
- Do not delay follow-up beyond 3 months: May miss treatment failure or adverse effects 1
- Do not continue treatment if <5% weight loss after 3 months: Early non-responders are unlikely to benefit from continued therapy 1
- Do not ignore peri-operative aspiration risk: Discontinue at least 3 weeks before elective surgery due to delayed gastric emptying 1
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors: Pharmacologically redundant and potentially harmful 1
- Do not prescribe to patients with personal or family history of medullary thyroid cancer or MEN 2: Absolute contraindications 1, 2