What are the GLP-1 (Glucagon-like peptide-1) receptor agonist options for weight loss?

GLP-1 Receptor Agonist Options for Weight Loss

Semaglutide and tirzepatide are the most effective GLP-1 receptor agonist options for weight loss, with tirzepatide showing the greatest effect at 21% weight loss at 72 weeks. 1

Available GLP-1 Options for Weight Loss

FDA-Approved Medications

1. Semaglutide (Wegovy)

   • Most effective pure GLP-1 agonist for weight loss
   • Produces 15-18% weight loss at higher doses
   • Weekly subcutaneous injection
   • FDA-approved specifically for weight management

2. Liraglutide (Saxenda)

   • Daily subcutaneous injection
   • Produces 5-10% weight loss
   • FDA-approved specifically for weight management

3. Tirzepatide (Zepbound)

   • Dual GIP/GLP-1 receptor agonist
   • Most potent weight loss medication in this class
   • Produces up to 21% weight loss at 72 weeks 1
   • Weekly subcutaneous injection
   • FDA-approved for weight management

Mechanism of Action

GLP-1 receptor agonists work through multiple mechanisms to promote weight loss:

• Delay gastric emptying, increasing satiety 1
• Suppress appetite through central nervous system effects on the hypothalamus 1
• Reduce food intake via central appetite suppression 1
• Improve insulin sensitivity and glucose metabolism

Dosing and Administration

• Semaglutide: Start at low dose (0.25mg weekly) and gradually titrate up to effective dose (typically 2.4mg weekly for weight management) 2
• Liraglutide: Start at 0.6mg daily, titrate weekly to target dose of 3.0mg daily
• Tirzepatide: Start at low dose and gradually titrate to effective dose (typically 5-15mg weekly)

Efficacy Comparison

• Tirzepatide: Greatest effect with mean weight loss of 21% at 72 weeks 1
• Semaglutide: 14-18% weight loss at higher doses 1
• Liraglutide: 6-8% weight loss 1

Side Effects and Considerations

Common Side Effects

• Gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 1, 2
• These typically improve with time and slow titration

Important Warnings

• Risk of thyroid C-cell tumors (contraindicated in patients with personal/family history of MTC or MEN2) 2
• Pancreatitis risk 2
• Diabetic retinopathy complications (particularly with semaglutide) 2
• Hypoglycemia risk when used with insulin secretagogues 2

Patient Selection and Monitoring

• Indicated for patients with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 1
• Screen for contraindications:
  • History of medullary thyroid carcinoma or MEN2
  • History of pancreatitis
  • Severe gastrointestinal disease
• Monitor for nutritional deficiencies, especially with significant weight loss 1
• Consider baseline assessment of muscle strength and body composition 3

Long-term Considerations

• Weight management pharmacotherapy should be continued beyond reaching weight loss goals to maintain health benefits 1
• Sudden discontinuation often results in weight regain and worsening of cardiometabolic risk factors 1, 4
• Consider combining with exercise for better long-term outcomes after medication discontinuation 4

Clinical Pearls

1. Start low, go slow with dosing to minimize gastrointestinal side effects
2. Combine with lifestyle modifications for optimal results
3. Monitor nutritional status in patients with significant weight loss
4. Consider cardiovascular benefits - semaglutide has demonstrated cardiovascular risk reduction in overweight/obese patients without diabetes 1
5. Plan for long-term therapy - these medications work best when used chronically, with weight regain common after discontinuation

For patients seeking weight loss, tirzepatide offers the greatest weight reduction potential, followed by semaglutide, with both significantly outperforming liraglutide in head-to-head comparisons.