What is the recommended treatment plan for weight loss using Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic)?

GLP-1 Receptor Agonists for Weight Loss: Treatment Plan

For weight loss using GLP-1 receptor agonists, a standardized titration protocol should be followed, starting with low doses and gradually increasing to the maintenance dose of 2.4 mg weekly for semaglutide, which results in 14.9-16.0% weight loss at 68 weeks. 1

Patient Selection and Initial Assessment

• Ideal candidates:

  • BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities
  • Lower BMI threshold (≥23 kg/m²) for Asian populations 1
  • Poor responders to lifestyle interventions alone

• Before initiating therapy, screen for:

  • Personal or family history of medullary thyroid cancer (contraindication)
  • Multiple endocrine neoplasia syndrome type 2 (contraindication)
  • Pregnancy (contraindication)
  • History of pancreatitis or gallbladder disease (use with caution) 1
  • Baseline dietary habits and nutritional status
  • Muscle strength and body composition

Dosing Protocol for Semaglutide

Follow this evidence-based titration schedule to minimize side effects:

Week	Semaglutide Dose
1-4	0.25 mg weekly
5-8	0.5 mg weekly
9-12	1.0 mg weekly
13-16	1.7 mg weekly
17+	2.4 mg weekly (maintenance)

• Administer as subcutaneous injection in abdomen, thigh, or upper arm 2
• No dose adjustment required for patients with renal or hepatic impairment 1, 2

Managing Side Effects

Gastrointestinal side effects are common (20-50% discontinuation rate in real-world settings) 3:

Adverse effect	Management
Nausea and vomiting	Avoid in gastroparesis
Dyspepsia	Start at low dose and titrate slowly
Diarrhea	Reduce meal size
Gastrointestinal reflux	Limit alcohol and carbonated drinks
Constipation	Avoid high-fat diet
Gallbladder disorders	Monitor for symptoms
Cardiac arrhythmia/tachycardia	If symptomatic, monitor and consider beta blockers

Nutritional and Lifestyle Support

• Implement complementary lifestyle interventions to:

  1. Mitigate GI side effects
  2. Enhance weight loss results
  3. Prevent nutritional deficiencies
  4. Preserve muscle mass 4

• Key nutritional recommendations:

  • Smaller, more frequent meals
  • Adequate protein intake (1.2-1.5 g/kg/day) to preserve muscle mass
  • Regular resistance training to prevent sarcopenia
  • Multivitamin supplementation to prevent deficiencies 4

Monitoring and Follow-up

• After establishing maintenance dose:

  • Follow-up at least quarterly
  • Monitor weight stability or continued gradual loss
  • Assess glycemic control if applicable
  • Manage side effects
  • Evaluate medication adherence 1

• Assess for:

  • Weight loss response (expect 5-18% weight reduction)
  • Improvements in comorbidities
  • Nutritional deficiencies
  • Muscle and bone loss 4

Long-term Maintenance

• Continue medication long-term after achieving weight loss goals - studies show significant weight regain (50-67% within one year) with discontinuation 1

• Maintenance options:

  1. Continue at full therapeutic dose (2.4 mg weekly) if well-tolerated
  2. Reduce to lowest effective dose that maintains weight loss (commonly 0.5-1.0 mg weekly)
  3. Consider intermittent therapy with close monitoring if continuous therapy isn't feasible 1

Real-world Considerations

• Weight loss in clinical practice tends to be lower than in clinical trials 3
• Highly adherent patients achieve results closer to those seen in trials 3
• Cost remains a significant barrier to long-term adherence 5
• Tirzepatide provides better value for money than semaglutide for weight reduction 1

Pitfalls to Avoid

• Discontinuing therapy prematurely (leads to weight regain)
• Inadequate dose titration (reduces efficacy)
• Failing to address side effects (leads to discontinuation)
• Not implementing complementary lifestyle interventions
• Overlooking nutritional deficiencies during rapid weight loss
• Neglecting muscle preservation strategies 4, 6