What are the considerations for prescribing Wegovy (semaglutide) for weight loss in adults with a body mass index (BMI) of 30 or higher, or those with a BMI of 27 or higher and at least one weight-related condition?

Wegovy (Semaglutide 2.4 mg) for Weight Management

Wegovy is highly effective for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with weight-related comorbidities, achieving 14.9-17.4% weight loss at 68 weeks, but requires lifelong use as discontinuation leads to significant weight regain. 1, 2

Patient Eligibility and FDA Approval

Wegovy is FDA-approved for adults with BMI ≥30 kg/m² without additional requirements, or BMI ≥27 kg/m² with at least one weight-related comorbidity including type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. 1

Additionally, Wegovy received FDA approval in 2024 to reduce cardiovascular death, myocardial infarction, and stroke in adults with established cardiovascular disease and BMI ≥27 kg/m², representing a 20% risk reduction. 3

Weight Loss Efficacy and Clinical Outcomes

Expected Weight Loss Results

In the pivotal STEP 1 trial, patients achieved mean weight loss of 14.9% at 68 weeks versus 2.4% with placebo (treatment difference 12.4 percentage points, 95% CI 11.5-13.4%). 1, 2

More granular outcomes show:

• 86.4% of patients achieved ≥5% weight loss (versus 31.5% placebo) 2
• 69.1% achieved ≥10% weight loss (versus 12.0% placebo) 2
• 50.5% achieved ≥15% weight loss (versus 4.9% placebo) 2

Real-world data from 8,177 patients using Wegovy with the WeGoTogether support program demonstrated even greater long-term results:

• Mean weight loss of 13.4% at 6 months 4
• 17.6% at 12 months 4
• 20.3% at 18 months 4
• 20.4% at 24 months 4

Cardiovascular Benefits Beyond Weight Loss

Semaglutide 2.4 mg reduces major adverse cardiovascular events by 20% (HR 0.80) in patients with obesity and established cardiovascular disease, including reductions in cardiovascular death, nonfatal MI, and nonfatal stroke. 3

The cardioprotective mechanisms include improved myocardial substrate utilization, anti-inflammatory and anti-atherosclerotic effects, reduced myocardial ischemia injury, lower systemic and pulmonary vascular resistance, and improved lipid profiles. 3

Dosing and Administration

Standard Titration Schedule

Wegovy requires gradual dose escalation over 16 weeks to minimize gastrointestinal side effects:

• Weeks 1-4: 0.25 mg weekly 3
• Weeks 5-8: 0.5 mg weekly 3
• Weeks 9-12: 1.0 mg weekly 3
• Weeks 13-16: 1.7 mg weekly 3
• Week 17 onward: 2.4 mg weekly (maintenance dose) 3

Wegovy is administered as a once-weekly subcutaneous injection in the abdomen, thigh, or upper arm, with similar bioavailability across all injection sites. 5

Missed Dose Management

If a dose is missed, administer as soon as possible if ≤4 days since the missed dose. If >4 days have passed, skip the dose and resume at the next scheduled time. 3

If 2 consecutive doses are missed, clinical judgment is required—resuming at the same dose can be considered if previously tolerated. If ≥3 consecutive doses are missed, consider restarting the titration schedule. 3

Safety Profile and Adverse Effects

Common Gastrointestinal Effects

Nausea, vomiting, and diarrhea are the most frequently reported adverse effects, occurring in a dose-dependent manner and typically being mild-to-moderate in severity. 1, 3

In clinical trials:

• Nausea occurred in 18-40% of patients 3
• Diarrhea in 12% 3
• Vomiting in 8-16% 3
• Constipation in 10-23% 3

These gastrointestinal effects are typically transient, subsiding with time and slow titration. 1, 2 Treatment discontinuation due to gastrointestinal events occurred in 4.5% of semaglutide patients versus 0.8% with placebo. 2

Serious Adverse Events

Serious adverse events occurred 38% more frequently with semaglutide versus placebo (95% CI 1.10-1.73), including pancreatitis, cholelithiasis, and cholecystitis. 3

Pancreatitis and gallbladder disease (cholelithiasis, cholecystitis) have been reported, though causality has not been definitively established. 1, 3 Patients should be monitored for persistent severe abdominal pain and discontinue if pancreatitis is suspected. 3

Absolute Contraindications

Wegovy is absolutely contraindicated in patients with:

• Personal or family history of medullary thyroid cancer 1, 3
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 3
• History of severe hypersensitivity reaction to semaglutide 3

This contraindication is based on animal studies showing thyroid C-cell tumors in rodents. 5

Wegovy is contraindicated in pregnancy and not recommended during breastfeeding. Women of reproductive potential should use reliable contraception. 1

Perioperative Considerations

For elective surgery requiring anesthesia, discontinue Wegovy at least 3 weeks (three half-lives) before the procedure due to delayed gastric emptying and aspiration risk. 3

Retained gastric contents are documented even after extended fasting periods, with 24.2% of semaglutide users showing increased residual gastric content versus 5.1% of controls, despite 10-14 day discontinuation and 12-hour fasting. 3

Critical Requirement: Lifelong Treatment

A critical limitation is that discontinuation leads to significant weight regain—patients regain one-half to two-thirds of lost weight within 1 year after stopping. 3, 6

In the STEP 1 extension study, participants who discontinued semaglutide after 68 weeks regained 11.6% of lost weight over the subsequent 52 weeks. 1 In STEP 4, participants transitioned to placebo after 20 weeks regained 6.9% of lost weight during 48 weeks of placebo administration. 1

This necessitates lifelong treatment for sustained benefits, which has significant cost implications at approximately $1,557-$1,619 per 30-day supply. 3

Mandatory Lifestyle Interventions

Wegovy must be used as an adjunct to lifestyle modifications—it is never prescribed as stand-alone treatment. 1

Required components include:

• Reduced-calorie diet with 500-kcal deficit below daily requirements 3
• Minimum 150 minutes per week of physical activity 1, 3
• Resistance training to preserve lean body mass 3
• Behavioral counseling and lifestyle modification support 1, 3

Monitoring and Follow-Up Schedule

Initial Titration Phase (First 16 Weeks)

Evaluate patients every 4 weeks during dose escalation to assess:

• Gastrointestinal tolerance and adverse effects 3
• Weight loss progress 3
• Blood pressure (may require antihypertensive adjustment) 3
• Signs of pancreatitis or gallbladder disease 3

Treatment Response Assessment

Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated therapeutic dose. 1, 3

If weight loss is <5% after 3 months at therapeutic dose, discontinue Wegovy and consider alternative approaches, as early non-responders are unlikely to benefit from continued therapy. 1

Conversely, patients achieving ≥5% weight loss after 3 months should continue long-term therapy, as further weight loss is likely with continued use. 1

Maintenance Phase Monitoring

After reaching maintenance dose, monitor at least every 3 months for:

• Weight stability and continued progress 3
• Cardiovascular risk factors 3
• Blood pressure 3
• Medication adherence 3
• Adverse effects 3

Special Populations and Considerations

Patients with Type 2 Diabetes

For patients with type 2 diabetes, Wegovy offers dual benefits of weight loss and improved glycemic control. 1, 3 However, weight loss appears lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%). 3

When initiating Wegovy in patients on insulin or sulfonylureas, reduce these medications to prevent hypoglycemia:

• Reduce basal insulin by 20% immediately 3
• Consider discontinuing or reducing sulfonylurea doses by 50% 3

Patients with Chronic Kidney Disease

No dose adjustment is required for any degree of renal impairment, including end-stage renal disease. 3, 5 Semaglutide reduces albuminuria and slows eGFR decline. 3

Patients with Cardiovascular Disease

Prioritize Wegovy for patients with established cardiovascular disease and obesity, as it provides proven cardiovascular benefit beyond weight loss. 3

"Ozempic Face" and Cosmetic Concerns

The term "Ozempic face" describes rapid facial volume loss creating a distorted appearance. 7 This is a natural consequence of rapid weight loss, not a novel adverse effect specific to semaglutide. 7

For patients considering cosmetic procedures while on Wegovy, discontinue at least 3 weeks before surgery requiring anesthesia, and consider gastric ultrasound pre-operatively to assess residual gastric contents. 3

Drug Interactions and Concomitant Medications

Semaglutide delays gastric emptying, which may affect absorption of oral medications. 5 However, clinical trials showed no clinically relevant interactions with metformin, oral contraceptives, warfarin, digoxin, or atorvastatin. 5

Do not use Wegovy with other GLP-1 receptor agonists or DPP-4 inhibitors. 3

Minimize medications that promote weight gain whenever possible, such as certain antidepressants, antipsychotics, antiepileptics, β-blockers, and corticosteroids. 1

Cost and Access Considerations

The average wholesale price is approximately $1,557-$1,619 per 30-day supply, requiring long-term financial planning for lifelong treatment. 3

Insurance authorization may be challenging, particularly for obesity management without diabetes. 3 The National Institute for Health and Care Excellence (UK) recommends semaglutide for weight management for a maximum treatment duration of 2 years. 6

Comparison with Alternative Medications

Tirzepatide (Mounjaro/Zepbound) demonstrates superior weight loss (20.9% at 72 weeks) compared to semaglutide 2.4 mg (14.9%), representing a 6% absolute advantage. 1, 3

However, semaglutide 2.4 mg has proven cardiovascular outcome benefits (26% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke, HR 0.74), making it the preferred choice for patients with established cardiovascular disease. 3

Liraglutide 3.0 mg daily achieves more modest weight loss of 5.24-6.1%, significantly less than semaglutide. 3

Common Pitfalls to Avoid

• Do not prescribe Wegovy without concurrent lifestyle interventions—medication alone without diet and exercise modifications yields suboptimal results. 1, 3
• Do not delay follow-up beyond 3 months during initial treatment—early non-responders should be identified and transitioned to alternative approaches. 1, 3
• Do not ignore perioperative aspiration risk—discontinue at least 3 weeks before elective surgery requiring anesthesia. 3
• Do not fail to counsel patients about lifelong treatment necessity—weight regain after discontinuation is substantial and predictable. 3, 6
• Do not overlook concomitant insulin or sulfonylurea dose reduction—hypoglycemia risk increases without appropriate medication adjustments. 3