What is the recommended dosage and administration of Glucagon-like peptide-1 (GLP-1) medications, such as liraglutide (Saxenda) or semaglutide (Wegovy), for weight loss?

GLP-1 Medication Dosing and Administration for Weight Loss

For weight loss, initiate semaglutide (Wegovy) at 0.25 mg subcutaneously once weekly, escalating every 4 weeks through 0.5 mg, 1.0 mg, 1.7 mg, to the maintenance dose of 2.4 mg weekly, which produces superior weight loss (14.9%) compared to liraglutide 3.0 mg daily (5.24 kg or approximately 6%) 1, 2.

Primary Medication Choice and Dosing

Semaglutide 2.4 mg (Wegovy) - First-Line Option

Semaglutide 2.4 mg weekly is the preferred GLP-1 receptor agonist for weight loss based on superior efficacy and once-weekly convenience 1, 3.

Titration Schedule:

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

Administration Details:

• Inject subcutaneously in abdomen, thigh, or upper arm 1
• Administer at any time of day, without regard to meals 1
• If a dose is missed, administer within 5 days; if more than 5 days elapsed, skip and resume regular schedule 1

Liraglutide 3.0 mg (Saxenda) - Alternative Option

Liraglutide 3.0 mg daily is a reasonable alternative if weekly injections are not feasible, though it produces less weight loss (5.24 kg vs 12.47 kg with semaglutide 2.4 mg) 2, 3.

Titration Schedule:

• Week 1: 0.6 mg subcutaneously once daily 4
• Week 2: 1.2 mg once daily 4
• Week 3: 1.8 mg once daily 4
• Week 4: 2.4 mg once daily 4
• Week 5 onward: 3.0 mg once daily (maintenance dose) 4

Administration Details:

• Inject subcutaneously in abdomen, thigh, or upper arm 4
• Administer at any time of day, independently of meals 4
• If more than 3 days elapsed since last dose, reinitiate at 0.6 mg to mitigate gastrointestinal symptoms 4

Mandatory Concomitant Interventions

GLP-1 receptor agonists must be combined with lifestyle modifications—this is not optional 1, 3:

• Caloric deficit: Minimum 500 kcal/day below total energy requirements 1
• Physical activity: Minimum 150 minutes weekly of structured exercise 1
• Behavioral counseling: Ongoing support for dietary changes 1
• Resistance training: Specifically recommended to preserve lean body mass during weight loss 3

Expected Efficacy and Treatment Duration

Weight Loss Outcomes:

• Semaglutide 2.4 mg: Mean 14.9% total body weight loss at 68 weeks (vs 2.4% with placebo) 1, 2
• Liraglutide 3.0 mg: Mean 5.24 kg weight loss 2
• 64.9% of patients on semaglutide 2.4 mg achieve ≥10% total body weight loss 3

Treatment Duration:

• GLP-1 receptor agonists should be considered lifelong therapy to maintain weight loss 1, 3
• After discontinuation, patients experience significant weight regain (11.6% of lost weight regained after 52 weeks) 3

Monitoring Requirements

Monitor at each visit (every 4 weeks during titration):

• Body weight 1
• Gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 1
• If symptoms are severe, maintain current dose longer before escalating 1

Additional monitoring:

• Blood pressure (may need to reduce antihypertensive medications as weight decreases) 3
• Glucose levels if patient has type 2 diabetes 1
• Nutritional status 1
• Signs of pancreatitis (persistent severe abdominal pain) 3
• Gallbladder disease symptoms 3

Adverse Effects Management

Common Gastrointestinal Effects:

• Nausea (44% with semaglutide at maximum dose) 1
• Diarrhea (32%) 1
• Vomiting (25%) 1
• Constipation (23%) 1

Mitigation Strategy:

• Gradual titration is the most effective strategy to reduce gastrointestinal symptoms 1, 3
• If symptoms are severe, extend time at current dose before escalating 1
• Reduce meal size and limit alcohol and carbonated drinks 3

Serious Adverse Events (Rare):

• Pancreatitis 3
• Gallbladder disease (cholelithiasis, cholecystitis) 3
• Risk of pulmonary aspiration under anesthesia even with extended fasting 3

Absolute Contraindications

Do not prescribe GLP-1 receptor agonists in patients with:

• Personal or family history of medullary thyroid cancer 3
• Multiple endocrine neoplasia syndrome type 2 3

Special Populations

Patients with Type 2 Diabetes:

• Weight loss is lower in individuals with diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 3, 5
• Monitor glucose more closely during dose titration 1
• May need to reduce other diabetes medications to prevent hypoglycemia 1

Patients with Cardiovascular Disease:

• Semaglutide 2.4 mg reduces major adverse cardiovascular events (HR 0.80) in patients with obesity and established cardiovascular disease 3
• This provides additional benefit beyond weight loss alone 3

Treatment Response Assessment

Evaluate efficacy at 12-16 weeks on maximum tolerated dose:

• If inadequate weight loss, consider intensifying treatment with additional approaches (metabolic surgery, additional pharmacologic agents, structured lifestyle programs) rather than discontinuing 3

Drug Interactions and Precautions

Do not combine with:

• Other GLP-1 receptor agonists 1
• DPP-4 inhibitors 1

Use caution with:

• Insulin or insulin secretagogues (increased hypoglycemia risk) 1
• Oral medications with narrow therapeutic indices (delayed gastric emptying may affect absorption) 3

Perioperative Considerations

For patients undergoing surgery:

• Retained gastric contents documented even after extended fasting periods 3
• Increased aspiration risk during anesthesia 3
• Discuss timing of discontinuation with anesthesia team well in advance 3