Which GLP-1 (Glucagon-Like Peptide-1) agonists are approved for weight loss?

GLP-1 Agonists Approved for Weight Loss

Currently, only liraglutide (3.0 mg daily) and semaglutide (2.4 mg weekly) are FDA-approved for weight loss in individuals with BMI ≥30 or BMI ≥27 with weight-related comorbidities. 1

FDA-Approved GLP-1 Agonists for Weight Loss

• Liraglutide (3.0 mg daily) was approved by the FDA in 2014 for weight management in adults with BMI ≥30 or BMI ≥27 with at least one weight-related comorbidity such as hypertension, type 2 diabetes, or obstructive sleep apnea 1
• Semaglutide (2.4 mg weekly) was approved by the FDA in 2021 for weight management with the same BMI criteria as liraglutide 1
• Tirzepatide (a dual GIP/GLP-1 receptor agonist) was approved by the FDA in November 2023 for weight management 1

Efficacy Comparison

• Semaglutide 2.4 mg weekly demonstrates superior weight loss compared to liraglutide:

  • Semaglutide produces mean weight loss of 14.9% from baseline in non-diabetic patients with obesity in the STEP trial 1
  • Liraglutide 3.0 mg daily achieves mean weight loss of 8.0% at 56 weeks 1, 2
  • Tirzepatide shows even greater efficacy with weight loss of 15-20.9% at higher doses (15 mg weekly) 1

• In patients without diabetes, GLP-1 receptor agonists produce substantially greater weight loss (6.1-17.4%) compared to patients with diabetes (4-6.2%) 1

Mechanism of Action for Weight Loss

• GLP-1 receptor agonists promote weight loss through multiple mechanisms:
  • Activation of GLP-1 receptors in the hypothalamus and brainstem to suppress appetite and increase satiety 1
  • Delayed gastric emptying, leading to prolonged feelings of fullness 1
  • Reduction in caloric intake through central nervous system effects 1, 3

Important Clinical Considerations

• Weight regain occurs after discontinuation of therapy, suggesting long-term use is necessary for sustained weight loss 1

• Common adverse effects include:

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea, dyspepsia) 1, 2
  • Potential for hypoglycemia, though risk is low without other precipitating factors 4, 2
  • Cardiac arrhythmia/tachycardia (monitor and consider beta blockers if symptomatic) 1

• Dosing recommendations:

  • Start at low doses and titrate upward slowly to minimize gastrointestinal side effects 1
  • For weight loss, higher doses are typically required compared to diabetes management (liraglutide 3.0 mg vs 1.8 mg; semaglutide 2.4 mg vs 1.0 mg) 1, 2

Additional Benefits Beyond Weight Loss

• Cardiovascular benefits: GLP-1 receptor agonists reduce risk of cardiovascular events in high-risk patients 1
• Improvements in metabolic parameters: reduction in HbA1c, improved lipid profiles 1, 2
• Potential benefits for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) 1

Off-Label Use

• In Australia, liraglutide is approved for weight loss, while semaglutide and dulaglutide are used off-label for obesity management 1
• Some clinicians may consider using lower doses of GLP-1 receptor agonists off-label for weight management, though efficacy may be reduced 4, 2