What is the recommended starting dose and treatment regimen for a GLP-1 (Glucagon-like peptide-1) agonist, such as liraglutide (Victoza), for a patient with type 2 diabetes?

GLP-1 Receptor Agonist Dosing and Treatment Regimen for Type 2 Diabetes

For patients with type 2 diabetes, the recommended starting dose for liraglutide (Victoza) is 0.6 mg subcutaneously once daily for one week, then increasing to 1.2 mg once daily, with further titration to 1.8 mg once daily if additional glycemic control is needed. 1

Initial Dosing and Titration

Liraglutide (Victoza)

• Start at 0.6 mg subcutaneously once daily for one week
  • This initial low dose is intended to reduce gastrointestinal side effects during titration 1
  • The 0.6 mg dose is not effective for glycemic control in adults and is only for initial titration 1
• After one week, increase to 1.2 mg subcutaneously once daily
• If additional glycemic control is required, increase to maximum recommended dose of 1.8 mg once daily after at least one week at the 1.2 mg dose 1

Other GLP-1 RAs

• Semaglutide (injectable): Start at 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg once weekly, with further titration to 1.0 mg if needed 2
• Dulaglutide: Start at 0.75 mg once weekly, then titrate to 1.5 mg once weekly as tolerated 3
• Exenatide: 5 μg twice daily initially, can increase to 10 μg twice daily after 1 month 3
• Lixisenatide: Start at 10 μg once daily, increase to 20 μg once daily after 14 days 3

Administration Guidelines

• Administer subcutaneously once daily at any time of day, independent of meals 1
• Inject in abdomen, thigh, or upper arm 1
• Rotate injection sites within the same region to reduce risk of cutaneous amyloidosis 1
• If a dose is missed, resume the once-daily regimen with the next scheduled dose 1
• If more than 3 days have elapsed since the last dose, reinitiate at 0.6 mg once daily to mitigate gastrointestinal symptoms 1

Dose Adjustments for Special Populations

Renal Impairment

• Liraglutide: No dose adjustment required, even with eGFR down to 15 ml/min/1.73 m² 2
• Exenatide: Not recommended for patients with eGFR <30 ml/min/1.73 m² 3
• Semaglutide: No dose adjustment required for eGFR ≥30 ml/min/1.73 m²; use with caution if <30 ml/min/1.73 m² 2

Monitoring and Follow-up

• Monitor blood glucose more closely during the first 4 weeks of therapy 3
• If A1C is well-controlled at baseline or there's a history of frequent hypoglycemic events, reduce dose of sulfonylurea by 50% or basal insulin dose by 20% when starting therapy 3
• Discontinue DPP-4 inhibitors before starting GLP-1 RAs 3
• Assess for common adverse effects, particularly gastrointestinal symptoms (nausea, vomiting, diarrhea) 3

Contraindications and Cautions

• Contraindicated in patients with:

  • Personal or family history of medullary thyroid carcinoma 1
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
  • Serious hypersensitivity to liraglutide or excipients 1
  • Pregnancy or breastfeeding 3

• Use with caution in patients with:

  • History of pancreatitis 3
  • History of gastroparesis 3
  • Diabetic retinopathy (particularly with semaglutide) 3

Clinical Considerations for Selection

• Consider GLP-1 RAs as first-line injectable therapy when priorities include:

  • Reducing cardiovascular events and mortality 3
  • Substantial weight loss 3
  • Once-weekly dosing options (for certain GLP-1 RAs) 3
  • Therapy when eGFR is consistently <45 ml/min/1.73 m² 3

• Consider alternative agents if patient has:

  • Persistent nausea even at low doses 3
  • History of pancreatitis 3
  • History of gastroparesis 3
  • History of MEN2 or medullary thyroid cancer 3

By following this structured approach to GLP-1 RA initiation and titration, clinicians can optimize glycemic control while minimizing adverse effects in patients with type 2 diabetes.