What is the treatment protocol for the Wegovy (semaglutide) medication for weight loss in adults with obesity?

Important Clarification: There is No Oral Wegovy Pill

Wegovy (semaglutide 2.4 mg) is only available as a once-weekly subcutaneous injection, not as an oral pill. 1, 2 You may be confusing this with Rybelsus (oral semaglutide), which is FDA-approved only for type 2 diabetes treatment at doses up to 14 mg daily—not for obesity management. 1

Wegovy Injectable Treatment Protocol

Patient Eligibility

• Adults with BMI ≥30 kg/m² qualify without additional requirements 1
• Adults with BMI ≥27 kg/m² qualify if they have at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, obstructive sleep apnea) 1

Absolute Contraindications

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

Standard Titration Schedule (16-Week Escalation)

The gradual dose escalation is critical to minimize gastrointestinal side effects: 1, 2

• Weeks 1-4: 0.25 mg 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, 2

Administration Details

• Inject subcutaneously once weekly in the abdomen, thigh, or upper arm 2
• Can be administered any day of the week, with or without meals 2
• If a dose is missed and the next scheduled dose is more than 2 days away, administer as soon as possible; if less than 2 days away, skip the missed dose 1
• If 2 consecutive doses are missed, resume at the same dose if previously tolerated well 1
• If 3 or more consecutive doses are missed, restart the titration schedule from 0.25 mg 1

Required Lifestyle Interventions

Wegovy must be combined with: 1, 3

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

Expected Weight Loss Outcomes

• Mean weight loss of 14.9-17.4% at 68 weeks in non-diabetic patients 1, 4, 3
• 64.9-79% of patients achieve ≥10% weight loss 1, 3
• 51-64% of patients achieve ≥15% weight loss 1, 3
• At 24 months, mean weight loss of approximately 20.4% has been observed in real-world settings 5

Treatment Response Assessment

• Evaluate efficacy at 12-16 weeks on maximum tolerated therapeutic dose 1
• If weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches 1
• Early responders (≥5% weight loss after 3 months) should continue long-term therapy 1

Common Side Effects

Gastrointestinal effects are most common (occur in 53% of patients): 2, 4, 3

• Nausea (most frequent) 2, 4
• Vomiting 2, 4
• Diarrhea 2, 4
• Constipation 2, 4
• Abdominal pain 2, 4

These are typically mild-to-moderate, transient, and decrease over time with continued exposure. 1, 4

Serious Adverse Events Requiring Monitoring

• Pancreatitis: Monitor for persistent severe abdominal pain; discontinue if suspected 1, 2
• Gallbladder disease: Cholelithiasis and cholecystitis reported 1, 2
• Acute kidney injury: Monitor renal function, especially with severe gastrointestinal symptoms causing dehydration 1
• Delayed gastric emptying: Creates aspiration risk during anesthesia—discontinue at least 3 weeks before elective surgery 1, 2

Concomitant Medication Adjustments

• Reduce insulin dose by 20% when initiating Wegovy to prevent hypoglycemia 1, 2
• Discontinue or reduce sulfonylurea doses by 50% 1, 2
• Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors 1

Long-Term Treatment Considerations

Wegovy typically requires lifelong use to maintain weight loss benefits: 1

• Sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 1
• After achieving weight loss goals, continue at maintenance dose with quarterly monitoring 1
• Cost is approximately $1,557-$1,619 per 30-day supply 1

Monitoring Schedule

During titration phase (first 16 weeks): 1

• Assess every 4 weeks for gastrointestinal tolerance, weight loss progress, and blood pressure 1

After reaching maintenance dose: 1

• Reassess at least every 3 months for continued weight loss progress, cardiovascular risk factors, medication adherence, and adverse effects 1

Special Populations

• No dose adjustment required for renal impairment, including end-stage renal disease 2
• No dose adjustment required for hepatic impairment 2
• Weight loss appears lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 1

Cardiovascular Benefits

For patients with established cardiovascular disease and BMI ≥27 kg/m²: 1

• 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) 1
• This makes Wegovy particularly valuable for patients with both obesity and cardiovascular disease 1