What is the role of Saxenda (liraglutide) in weight loss management?

Role of Saxenda (Liraglutide) in Weight Loss Management

Saxenda (liraglutide 3.0 mg) is an effective FDA-approved medication for chronic weight management in patients with obesity, producing 5.8-8.0% weight loss when used as an adjunct to lifestyle modifications. 1

Mechanism of Action

• Liraglutide is a GLP-1 receptor agonist with 97% homology to human GLP-1, a gut-derived incretin hormone 1, 2
• Weight loss is mediated through multiple mechanisms:
  • Reduced appetite and increased satiety via action on the hypothalamus 1, 2
  • Delayed gastric emptying, which helps reduce food intake 2
  • Decreased glucagon secretion in a glucose-dependent manner 2

FDA Approval and Dosing

• FDA approved in 2014 specifically for chronic weight management in patients with obesity 1
• Indicated for:
  • BMI ≥30 kg/m² or
  • BMI ≥27 kg/m² with at least one weight-related comorbidity (such as hypertension, dyslipidemia, or type 2 diabetes) 1
• Administered as a subcutaneous injection once daily 1
• Dosing protocol:
  • Start at 0.6 mg daily for 1 week
  • Increase by 0.6 mg weekly until reaching the target dose of 3.0 mg 1
  • Slower dose titration can help manage gastrointestinal side effects 1
  • Should be discontinued if 4% weight loss is not achieved after 16 weeks 1

Clinical Efficacy

• In the SCALE trial, patients treated with liraglutide 3.0 mg achieved:
  • Mean weight loss of 8.0% after 56 weeks (compared to 2.6% with placebo) 3, 4
  • 63.2% of patients lost at least 5% of their body weight (vs 27.1% with placebo) 4
  • 33.1% lost more than 10% of their body weight (vs 10.6% with placebo) 4
• In patients with OSA, liraglutide demonstrated:
  • Decreased body weight (mean difference -4.9 kg)
  • Reduced BMI (mean difference -1.6 kg/m²)
  • Decreased neck circumference (mean difference -0.8 cm)
  • Improved AHI (mean difference -6.1 events/h) 1
• Weight loss with liraglutide correlates with improvements in metabolic parameters:
  • Decreased waist circumference
  • Reduced triglycerides
  • Improved insulin resistance
  • Decreased blood pressure
  • Increased HDL-C 3

Side Effects and Safety Considerations

• Most common adverse effects are gastrointestinal:
  • Nausea (most frequent)
  • Vomiting
  • Diarrhea
  • Constipation 1, 3
• Other potential side effects include:
  • Headache
  • Hypoglycemia (particularly in patients with diabetes) 1, 3
• Serious safety concerns:
  • Potential risk of pancreatitis
  • Thyroid C-cell tumors in rodents (contraindicated in patients with personal/family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2) 1
  • Contraindicated in pregnancy 1

Comparison to Newer GLP-1 Receptor Agonists

• More recent GLP-1 receptor agonists have shown greater efficacy:
  • Semaglutide 2.4 mg weekly produces mean weight loss of 14.9-16.0% at 68 weeks 1
  • Tirzepatide (dual GIP/GLP-1 receptor agonist) produces mean weight loss of 15.0-20.9% at 72 weeks 1
• However, liraglutide remains an important option due to:
  • Established safety profile
  • Wider availability
  • Potentially lower cost compared to newer agents 1

Practical Considerations

• Liraglutide should be used as an adjunct to comprehensive lifestyle modifications including diet and exercise 1, 3
• Long-term use is necessary to maintain weight loss, as weight regain commonly occurs after discontinuation 5
• Patients should be monitored for:
  • Weight loss response (discontinue if <4% weight loss after 16 weeks) 1
  • Gastrointestinal side effects (can be managed with slower dose titration) 1
  • Signs/symptoms of pancreatitis 1
• Cost considerations: Average wholesale price is approximately $1,385 per month for the maintenance dose 1

Clinical Pearl

• Slower dose titration than the standard weekly increase can help minimize gastrointestinal side effects while still achieving therapeutic efficacy 1
• For patients who cannot tolerate the full 3.0 mg dose, even lower doses may provide some weight loss benefit, though potentially less than the maximum dose 2