Wegovy (Semaglutide 2.4 mg) for Weight Loss and Diabetes Management
Primary Recommendation
Wegovy (semaglutide 2.4 mg weekly) is indicated for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity, and provides proven cardiovascular risk reduction in patients with established cardiovascular disease. 1
Patient Eligibility Criteria
BMI Requirements
- BMI ≥30 kg/m² (obesity) without additional requirements 2
- BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity including:
Absolute Contraindications
- Personal or family history of medullary thyroid cancer 1, 2, 3
- Multiple endocrine neoplasia syndrome type 2 1, 2, 3
- Pregnancy or breastfeeding 1
Pre-Treatment Evaluation
Required Screening
- Screen for personal/family history of medullary thyroid cancer or MEN2 syndrome 2, 4
- Comprehensive metabolic panel including renal function (eGFR) and liver enzymes 2
- Lipid panel (total cholesterol, LDL, HDL, triglycerides) 2
- Document history of pancreatitis (use with caution if present) 2
- Review all current medications to identify weight-promoting drugs and consider alternatives 2
Baseline Measurements
Dosing and Titration Schedule
Standard Titration Protocol
Follow this exact schedule to minimize gastrointestinal adverse effects: 2
- Weeks 1-4: 0.25 mg weekly 2
- Weeks 5-8: 0.5 mg weekly 2
- Weeks 9-12: 1.0 mg weekly 2
- Weeks 13-16: 1.7 mg weekly 2
- Week 17 onward: 2.4 mg weekly (maintenance dose) 2
Administration Details
- Subcutaneous injection once weekly 3
- Can be administered in abdomen, thigh, or upper arm 3
- No dose adjustment needed for renal or hepatic impairment 3
- Steady-state exposure achieved after 4-5 weeks 3
- Elimination half-life approximately 1 week 3
Missed Dose Management
- If 2 consecutive doses missed: resume at same dose if previously tolerated 2
- If 3+ consecutive doses missed: restart titration schedule 2
Expected Weight Loss Outcomes
Clinical Trial Data
- Mean weight loss at 68 weeks: 14.9% (vs 2.4% placebo) 1, 2
- Patients achieving ≥10% weight loss: 64.9% 2
- Patients achieving ≥20% weight loss: 13.1% at 6 months, 43.3% at 12 months, 50.5% at 24 months 5
Real-World Data
- 6 months: -13.4% mean weight loss 5
- 12 months: -17.6% mean weight loss 5
- 18 months: -20.3% mean weight loss 5
- 24 months: -20.4% mean weight loss 5
Cardiovascular Benefits
FDA-Approved Cardiovascular Indication
In 2024, Wegovy was FDA-approved to reduce cardiovascular death, heart attack, and stroke in adults with obesity or overweight and established CVD. 1
SELECT Trial Results (Most Recent High-Quality Evidence)
- Patient population: Over 17,600 participants age ≥45 years, BMI ≥27 kg/m², with prior MI, stroke, peripheral arterial disease, revascularization, or amputation 1
- Primary outcome: Major cardiovascular events occurred in 6.5% with Wegovy vs 8% with placebo 1
- Risk reduction: 20% reduction in cardiovascular death by semaglutide 1
- Composite outcome reduction: 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) 1, 2
Additional Cardiovascular Effects
- Reduces LDL cholesterol 1
- Lowers blood pressure 1
- Decreases inflammatory markers like C-reactive protein 1
Diabetes Management Benefits
Glycemic Control
- HbA1c reduction: Approximately 1.4-1.48% from baseline 2, 3
- Fasting glucose reduction: 29 mg/dL (22% reduction) 3
- 2-hour postprandial glucose reduction: 74 mg/dL (36% reduction) 3
- Mean 24-hour glucose reduction: 30 mg/dL (22% reduction) 3
Mechanism in Diabetes
- Stimulates glucose-dependent insulin secretion 3
- Lowers glucagon secretion in glucose-dependent manner 3
- Delays gastric emptying in early postprandial phase 3
- Minimal hypoglycemia risk when used as monotherapy 2
Type 2 Diabetes Risk Reduction
- 10-year T2D risk reduction: 61.1% at 68 weeks (vs 12.9% placebo) 6
- Maintained at 104 weeks: 60.0% reduction (vs 3.5% increase with placebo) 6
Required Lifestyle Interventions
Wegovy must be combined with the following lifestyle modifications: 2
- Dietary intervention: 500-kcal reduction below daily requirements 2
- Physical activity: Minimum 150 minutes per week 2
- Resistance training: To preserve lean body mass 2
- Behavioral counseling: Structured lifestyle management support 2
Monitoring Schedule
During Titration (Weeks 1-16)
- Every 4 weeks: 2
After Reaching Maintenance Dose
- Every 3 months minimum: 2
Efficacy Assessment
- Evaluate at 12-16 weeks on maximum tolerated dose: 2
Adverse Effects and Management
Most Common Side Effects
Gastrointestinal effects are dose-dependent and typically mild-to-moderate: 2
- Nausea: 17-44% of patients 2
- Diarrhea: 12-32% of patients 2
- Vomiting: 7-25% of patients 2
- Constipation: 10-23% of patients 2
Mitigation Strategies
- Slow titration following standard schedule 2
- Reduce meal size 2
- Limit alcohol and carbonated beverages 2
- Effects typically decrease over time 2
Serious Adverse Events (Rare)
- Pancreatitis: Monitor for persistent severe abdominal pain 1, 2
- Gallbladder disease: Cholelithiasis and cholecystitis 1, 2
- Serious adverse events: 38% higher rate vs placebo (95% CI 1.10-1.73) 2
Treatment Discontinuation
- Discontinuation rate: 34 more per 1000 patients vs placebo, primarily from GI effects 2
Special Considerations
Peri-Operative Management
Critical aspiration risk exists even with extended fasting: 2
- For non-diabetic patients: Discontinue semaglutide for at least 3 weeks (three half-lives) before surgery 2
- For diabetic patients: Consult endocrinology to weigh risks/benefits of holding medication 2
- Rationale: Retained gastric contents documented even after extended fasting periods; 24.2% of semaglutide users had increased residual gastric content vs 5.1% controls despite 10-14 day discontinuation and 12-hour fasting 2
- Consider gastric ultrasound pre-operatively to assess residual gastric contents 2
Medication Interactions
- Do not combine with: Other GLP-1 receptor agonists or DPP-4 inhibitors 2
- Use caution with: Insulin or insulin secretagogues due to hypoglycemia risk 1, 2
- Reduce sulfonylureas: Due to increased hypoglycemia risk 2
Renal and Hepatic Impairment
- No dose adjustment required for any degree of renal or hepatic impairment 3
- Safe in end-stage renal disease 3
Cardiovascular Disease Patients
Prioritize semaglutide 2.4 mg in patients with established CVD due to proven cardiovascular benefit. 2
Long-Term Treatment Considerations
Lifelong Treatment Necessity
Wegovy must be used lifelong to maintain weight loss benefits. 2
- Weight regain after discontinuation: 11.6% of lost weight regained after 52 weeks 2
- Sudden discontinuation: Results in regain of one-half to two-thirds of lost weight within 1 year 2
Maintenance Strategy After Achieving Weight Loss Goals
Continue full-dose therapy indefinitely: 2
- Maintain 2.4 mg weekly dose 2
- Monitor quarterly for weight stability, cardiovascular risk factors, and medication tolerance 2
- If weight regain occurs despite ongoing therapy: increase to maximum approved doses, add structured lifestyle programs, or consider metabolic surgery if BMI ≥30 kg/m² 2
Cost Considerations
- Average wholesale price: Approximately $1,557-$1,600 per 30-day supply 2
- Insurance coverage varies significantly and may be limited for obesity management without diabetes 2
- Lifelong treatment requires long-term financial planning 2
Treatment Intensification
If Inadequate Response
When patients fail to achieve goals after 3 months at maximum tolerated dose: 2
- Add structured lifestyle management programs 2
- Consider metabolic surgery if BMI ≥30 kg/m² 2
- Evaluate for additional pharmacologic agents 2
Comparison to Alternative Therapies
Tirzepatide (Superior Weight Loss)
- Tirzepatide achieves 20.9% weight loss vs semaglutide's 14.9% 2
- Consider tirzepatide when maximum weight loss is primary goal 2
When to Choose Semaglutide Over Tirzepatide
- Established cardiovascular disease: Semaglutide has proven cardiovascular outcome benefits 2
- Cost/insurance barriers: Tirzepatide faces more authorization barriers 2
Common Pitfalls to Avoid
- Do not skip the titration schedule - rapid dose escalation increases GI side effects 2
- Do not discontinue prematurely - weight loss continues to improve through 24 months 5
- Do not ignore peri-operative aspiration risk - hold medication appropriately before surgery 2
- Do not combine with other GLP-1 agonists - pharmacologically redundant and potentially harmful 2
- Do not expect sustained weight loss after discontinuation - lifelong treatment is necessary 2
- Do not overlook blood pressure monitoring - antihypertensive adjustments may be needed as weight decreases 2