What is the recommended dosing regimen for Wegovy (semaglutide) in chronic weight management?

Wegovy (Semaglutide 2.4 mg) Dosing for Chronic Weight Management

For chronic weight management, initiate Wegovy at 0.25 mg subcutaneously once weekly, then escalate the dose every 4 weeks through 0.5 mg, 1.0 mg, 1.7 mg, to the maintenance dose of 2.4 mg once weekly. 1

Dose Escalation Schedule

The FDA-approved titration regimen follows a structured 5-step escalation protocol 2:

• Week 1-4: 0.25 mg once weekly
• Week 5-8: 0.5 mg once weekly
• Week 9-12: 1.0 mg once weekly
• Week 13-16: 1.7 mg once weekly
• Week 17 onward: 2.4 mg once weekly (maintenance dose) 1, 2

This gradual titration is critical—it significantly reduces gastrointestinal adverse events, particularly nausea (44%) and vomiting (25%) that occur at maximum doses. 3 If gastrointestinal symptoms are severe at any dose level, maintain the current dose for an additional 4 weeks before advancing to minimize side effects. 3

Administration Details

• Route: Subcutaneous injection once weekly at any time of day 1, 2
• Injection sites: Abdomen, thigh, or upper arm (similar bioavailability across all sites) 2
• Timing: Can be administered without regard to meals 2
• Steady state: Achieved after 4-5 weeks of once-weekly administration 2

Expected Weight Loss Outcomes

The 2.4 mg maintenance dose produces substantial weight reduction 4, 5:

• 6 months: Mean weight loss of 13.4% 5
• 12 months: Mean weight loss of 17.6% (vs. 2.4% with placebo) 4, 5
• 18 months: Mean weight loss of 20.3% 5
• 24 months: Mean weight loss of 20.4% 5

At 12 months, 69-79% of patients achieve ≥10% weight loss and 51-64% achieve ≥15% weight loss with semaglutide 2.4 mg, compared to only 12-27% and 5-13% respectively with placebo. 4

Mandatory Concomitant Interventions

Semaglutide must be combined with lifestyle modifications—this is not optional. 1, 3 The American Gastroenterological Association requires 3:

• Caloric deficit: Minimum 500 kcal/day below total energy requirements 3
• Physical activity: Minimum 150 minutes weekly of structured exercise 3
• Behavioral counseling: Ongoing support for dietary and behavioral changes 3

Treatment Duration and Discontinuation

Semaglutide should be considered lifelong therapy to maintain weight loss. 1, 3 Weight management pharmacotherapy indicated for chronic use must be continued beyond reaching weight loss goals to maintain health benefits, as sudden discontinuation results in significant weight regain and worsening of cardiometabolic risk factors. 1, 3

Renal Dosing Considerations

No dose adjustments are required for renal impairment, including end-stage renal disease. 1 This was demonstrated in studies across all degrees of renal function (mild, moderate, severe, ESRD) showing no clinically relevant impact on semaglutide pharmacokinetics. 2

Monitoring Requirements

Monitor the following parameters 3:

• Body weight: Every 4 weeks during dose titration 3
• Gastrointestinal symptoms: Assess at each visit; if severe, delay dose escalation 3
• Glucose monitoring: More frequent if patient has concomitant type 2 diabetes 3
• Nutritional status: Screen for malnutrition in patients with significant weight loss 1

Treatment Response Evaluation

If patients fail to achieve adequate weight loss, intensify treatment rather than discontinue. 1 The American Diabetes Association recommends reevaluating and adding additional approaches (metabolic surgery, additional pharmacologic agents, structured lifestyle programs) for those not reaching goals. 1

Common Pitfalls to Avoid

• Rapid dose escalation: This dramatically increases gastrointestinal side effects; always follow the 4-week intervals 3, 2
• Premature discontinuation: Stopping therapy leads to weight regain; continue indefinitely for sustained benefit 1, 3
• Inadequate lifestyle support: Pharmacotherapy alone is insufficient; structured dietary and exercise programs are mandatory 3
• Ignoring concomitant medications: Review and minimize weight-promoting medications (antipsychotics, certain antidepressants, glucocorticoids, beta-blockers) whenever possible 1

Additional Cardiometabolic Benefits

Beyond weight loss, semaglutide 2.4 mg provides weight-independent benefits including improvements in blood pressure, atherogenic lipids, inflammation, obstructive sleep apnea, and metabolic dysfunction-associated steatotic liver disease. 1 Notably, semaglutide 2.4 mg reduces major adverse cardiovascular events in patients with obesity and established cardiovascular disease. 1