What are the initial treatment options and dosing recommendations for Glucagon-like peptide-1 (GLP-1) analogues, such as liraglutide (Victoza), semaglutide (Ozempic), and dulaglutide (Trulicity)?

GLP-1 Receptor Agonist Treatment Options and Dosing Recommendations

GLP-1 receptor agonists should be initiated with gradual dose titration to minimize gastrointestinal side effects, with specific starting doses and titration schedules varying by medication. 1

Initial Treatment Options and Dosing for Common GLP-1 Analogues

Liraglutide (Victoza)

• Starting dose: 0.6 mg subcutaneously once daily for 7 days 1, 2
• Titration schedule:
  • Increase to 1.2 mg daily after 1 week
  • Further increase to 1.8 mg daily after another week if needed for glycemic control
  • For obesity management: continue titration to 2.4 mg and then 3.0 mg daily at weekly intervals 1
• Administration: Can be injected at any time of day, independent of meals 3
• No dosage adjustment required for renal impairment 1

Semaglutide (Ozempic)

• Starting dose: 0.25 mg subcutaneously once weekly for 4 weeks 1
• Titration schedule:
  • Increase to 0.5 mg weekly after 4 weeks
  • Further increase to 1.0 mg weekly after another 4 weeks if needed
  • For weight management: continue titration to 1.7 mg and then 2.4 mg weekly at 4-week intervals 1
• No dosage adjustment required for renal impairment 1

Dulaglutide (Trulicity)

• Starting dose: 0.75 mg subcutaneously once weekly 1, 4
• Titration schedule:
  • Increase to 1.5 mg weekly after at least 4 weeks if needed for additional glycemic control
  • Further increases in 1.5 mg increments (to maximum 4.5 mg weekly) can be considered after at least 4 weeks at each dose 4
• No dosage adjustment required for renal impairment 1

Administration Guidelines

General Administration Instructions

• Administer subcutaneously in the abdomen, thigh, or upper arm 4
• Rotate injection sites with each dose 4
• For weekly GLP-1 RAs, administer on the same day each week when possible 4

Missed Dose Management

• For once-daily medications (liraglutide): Take as soon as noticed if within the same day 2
• For once-weekly medications (semaglutide, dulaglutide):
  • If ≥3 days (72 hours) until next scheduled dose: Administer missed dose as soon as possible
  • If <3 days before next scheduled dose: Skip the missed dose and resume regular schedule 4

Special Considerations and Precautions

Gastrointestinal Side Effects Management

• Gradual dose titration is essential to minimize nausea, vomiting, and diarrhea 1
• GI side effects are typically transient and diminish over time 3, 5
• Nausea occurs in approximately 40% of patients on liraglutide (vs. 14.8% with placebo) 1

Drug Interactions and Contraindications

• Do not use with other GLP-1 RAs or DPP-4 inhibitors 1
• Use caution with insulin or sulfonylureas due to increased hypoglycemia risk; consider dose reduction of these agents 1
• Contraindicated in patients with:
  • Personal or family history of medullary thyroid carcinoma 2, 4
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2, 4
  • History of serious hypersensitivity to the drug 4

Renal Considerations

• Dulaglutide, liraglutide, and semaglutide require no dose adjustment for renal impairment 1
• Other GLP-1 RAs like exenatide and lixisenatide have restrictions for use in advanced kidney disease 1

Resuming After Missed Multiple Doses

• If >2 consecutive doses are missed, clinical judgment is required 1
• For patients who tolerated the medication well, resuming at the same dose may be considered 1
• Otherwise, consider lowering the dose or restarting the titration schedule if ≥3 consecutive doses were missed 1

Clinical Benefits Beyond Glycemic Control

• Weight reduction: GLP-1 RAs are associated with significant weight loss 1, 6
• Cardiovascular benefits: Dulaglutide, liraglutide, and semaglutide have demonstrated cardiovascular outcome benefits 1
• Renal benefits: GLP-1 RAs may reduce albuminuria and slow eGFR decline 1

By following these dosing recommendations and considering the special precautions, clinicians can optimize the use of GLP-1 receptor agonists while minimizing adverse effects and maximizing benefits for patients with type 2 diabetes.