What is the recommended dosage and administration of Trelagliptin (Sagliptin) for patients with type 2 diabetes mellitus, particularly those with impaired renal function?

Trelagliptin Dosage and Administration for Type 2 Diabetes with Renal Impairment

For patients with type 2 diabetes mellitus and impaired renal function, trelagliptin (Sagliptin) should be administered at a reduced dose of 25 mg once weekly when creatinine clearance is <30 mL/min or in end-stage renal disease.

Dosing Algorithm Based on Renal Function

• Normal to moderate renal function (eGFR ≥30 mL/min/1.73 m²)

  • Standard dose: 100 mg orally once weekly
  • Can be taken regardless of meals

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD

  • Reduced dose: 25 mg orally once weekly 1
  • Clinical studies have demonstrated both safety and efficacy at this reduced dose

Efficacy in Renal Impairment

Trelagliptin 25 mg once weekly has demonstrated significant glycemic control in patients with severe renal impairment. In a randomized phase 3 study, patients with severe renal impairment or ESRD showed a mean HbA1c reduction of 0.71% compared to placebo after 12 weeks of treatment 1. This efficacy was maintained throughout the 52-week follow-up period.

Safety Considerations

• Adverse Events: The safety profile in patients with renal impairment is similar to that in patients with normal renal function
• Hypoglycemia Risk: Low risk of hypoglycemia when used as monotherapy 2
• Monitoring Requirements:
  • Assess renal function before initiating treatment and periodically thereafter
  • Monitor for signs of adverse events, which are typically mild to moderate in severity

Place in Therapy for Diabetic Kidney Disease

When considering trelagliptin for patients with type 2 diabetes and CKD, it's important to note the current treatment algorithm recommended by guidelines:

1. First-line therapy: Metformin (if eGFR ≥30 mL/min/1.73 m²) with dose reduction to 1000 mg daily for eGFR 30-44 mL/min/1.73 m² 3

2. Second-line therapy: SGLT2 inhibitor with proven kidney or cardiovascular benefit for patients with eGFR ≥20 mL/min/1.73 m² 3

3. Third-line therapy: GLP-1 receptor agonist with proven cardiovascular benefit for patients who don't meet glycemic targets with metformin and/or SGLT2i 3

4. Fourth-line therapy: DPP-4 inhibitors like trelagliptin may be considered when other agents are contraindicated or not tolerated

Advantages of Trelagliptin

• Once-weekly dosing: Improves medication adherence compared to daily DPP-4 inhibitors 4
• Weight neutrality: Does not cause weight gain unlike some other antidiabetic medications 2
• Low hypoglycemia risk: Minimal risk when used as monotherapy 2
• Renal dosing option: Can be used in severe renal impairment with appropriate dose adjustment 1

Clinical Pearls and Pitfalls

• Pitfall: Failing to reduce the dose in severe renal impairment could potentially lead to drug accumulation
• Pitfall: Not recognizing that trelagliptin, while convenient, is not prioritized over SGLT2 inhibitors or GLP-1 receptor agonists in current guidelines for patients with diabetic kidney disease
• Pearl: The once-weekly dosing may significantly improve adherence in patients struggling with multiple daily medications

Monitoring Recommendations

• Assess renal function before initiating treatment
• Monitor HbA1c every 3-6 months
• Evaluate for adverse events at each clinical visit
• Re-assess renal function periodically, especially if at risk for worsening kidney function

Trelagliptin represents a convenient once-weekly option for patients with type 2 diabetes, including those with renal impairment, when dosed appropriately according to kidney function.