What is the recommended dosing regimen for semaglutide (glucagon-like peptide-1 receptor agonist) for weight loss in an adult patient with obesity or overweight and at least one weight-related condition?

Semaglutide Dosing for Weight Loss

For weight loss in adults with obesity (BMI ≥30) or overweight (BMI ≥27 with weight-related conditions), semaglutide should be initiated at 0.25 mg subcutaneously once weekly and titrated to a maintenance dose of 2.4 mg weekly over 16 weeks. 1, 2

Standard Titration Schedule

The dose escalation follows a specific 16-week protocol 2, 3:

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

This gradual titration is critical for minimizing gastrointestinal side effects, which occur in the majority of patients but are typically mild-to-moderate and transient. 2, 3

Administration Details

• Administer subcutaneously in the abdomen, thigh, or upper arm at any time of day, with or without meals 4
• If a dose is missed, administer within 5 days; if more than 5 days have passed, skip the missed dose and resume the regular schedule 4
• If 2 consecutive doses are missed: Resume at the same dose if previously well-tolerated 2
• If 3 or more consecutive doses are missed: Consider restarting the titration schedule from 0.25 mg 2

Expected Weight Loss Outcomes

The 2.4 mg maintenance dose produces substantial weight reduction 1, 5, 6:

• Mean weight loss: 14.9-17.4% at 68 weeks in patients without diabetes 5, 6
• Mean weight loss: 6.34% in patients with type 2 diabetes 7
• ≥10% weight loss achieved by: 69-79% of patients without diabetes 6
• ≥15% weight loss achieved by: 51-64% of patients without diabetes 6

Weight loss is consistently greater in individuals without diabetes compared to those with diabetes, likely due to differences in insulin resistance and compensatory metabolic mechanisms. 2, 7

Mandatory Lifestyle Interventions

Semaglutide must be combined with lifestyle modifications 1, 2, 3:

• Caloric deficit: Minimum 500 kcal/day reduction below daily requirements
• Physical activity: Minimum 150 minutes weekly of structured exercise
• Resistance training: Essential to preserve lean body mass during weight loss
• Behavioral counseling: Ongoing support for dietary and behavioral changes

Monitoring Requirements

During Titration (Weeks 1-16)

• Body weight: Every 4 weeks 2, 3
• Gastrointestinal symptoms: At each visit; if severe, maintain current dose longer before escalating 3
• Blood glucose: More frequent monitoring if patient has type 2 diabetes, especially if on insulin or sulfonylureas 3
• Blood pressure: Monitor closely as antihypertensive requirements may decrease with weight loss 2

After Reaching Maintenance Dose

• Treatment response evaluation: At 12-16 weeks on maximum tolerated dose 2, 3
• Ongoing monitoring: Every 3 months minimum for weight, blood pressure, cardiovascular risk factors, and medication tolerance 2
• Discontinuation criteria: Consider stopping if <5% weight loss after 12 weeks at maximum dose 2, 3

Common Adverse Effects and Management

Gastrointestinal effects are the most common adverse events 2, 5, 6:

• Nausea: 18-44% of patients
• Diarrhea: 12-32% of patients
• Vomiting: 8-25% of patients
• Constipation: 10-23% of patients

Management strategies 2, 3:

• Slow titration (as outlined above)
• Reduce meal size
• Limit alcohol and carbonated beverages
• If symptoms are severe, maintain current dose for additional weeks before escalating

Treatment discontinuation due to gastrointestinal events occurs in approximately 4.5% of patients. 5

Serious Adverse Events and Contraindications

Absolute Contraindications 1, 2

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2

Serious but Rare Risks 1, 2, 6

• Pancreatitis: Monitor for persistent severe abdominal pain
• Gallbladder disease: Including cholelithiasis and cholecystitis
• Acute kidney injury: Use caution in patients with renal disease

Drug Interactions 2

• Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors
• Use caution with insulin or insulin secretagogues due to hypoglycemia risk

Duration of Treatment

Semaglutide should be considered lifelong therapy to maintain weight loss. 2, 3 After discontinuation, patients regain 50-67% of lost weight within one year, with worsening of cardiometabolic risk factors. 2 The medication must be used chronically, similar to other treatments for chronic diseases. 1

Cardiovascular Benefits

Beyond weight loss, semaglutide 2.4 mg provides significant cardiovascular benefits 2:

• 20% reduction in composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) in patients with obesity and established cardiovascular disease
• Improvements in blood pressure, atherogenic lipids, and inflammatory markers
• Benefits on physical function and quality of life

Special Populations

Patients with type 2 diabetes: Semaglutide offers dual benefits of weight loss and improved glycemic control, though weight loss magnitude is lower (approximately 6-9.6%) compared to non-diabetic patients. 2, 7, 6

Patients with cardiovascular disease: Semaglutide 2.4 mg is particularly valuable due to proven cardiovascular risk reduction beyond weight loss effects. 2

Cost Considerations

The average wholesale price is approximately $1,557-$1,600 per 30-day supply, requiring long-term financial planning and insurance authorization. 2 Patients should be counseled about the chronic nature of treatment and associated costs before initiation.