What is the recommended dose and weekly dosing schedule of trelagliptin for adults with type 2 diabetes mellitus, and are dose adjustments needed for renal impairment, hepatic impairment, or in elderly patients?

Trelagliptin Dosing and Administration

Trelagliptin is administered as a single 100 mg oral dose once weekly in patients with normal renal function, making it the only DPP-4 inhibitor that requires dosing just once per week rather than daily. 1

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Standard Dosing for Normal Renal Function

• The recommended dose is 100 mg orally once weekly for patients with type 2 diabetes and adequate kidney function (creatinine clearance ≥30 mL/min). 1, 2
• Trelagliptin can be taken at any time of day, with or without food, providing flexibility in administration. 2
• The once-weekly dosing schedule is designed to improve medication adherence compared to daily DPP-4 inhibitors while maintaining similar glycemic efficacy. 1, 3

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Dose Adjustments for Renal Impairment

Severe Renal Impairment or End-Stage Renal Disease

• For patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease requiring hemodialysis, reduce the dose to 25 mg once weekly. 4
• This 25 mg weekly dose provides effective glycemic control (mean HbA1c reduction of -0.71% at 12 weeks) with no major safety concerns in patients with advanced kidney disease. 4
• No additional dose adjustment is needed for patients on hemodialysis—the 25 mg weekly dose is appropriate regardless of dialysis timing. 4

Moderate Renal Impairment

• For patients with moderate renal impairment (creatinine clearance 30–50 mL/min), initiate conservatively at 50 mg once weekly and monitor closely for hypoglycemia, particularly if combined with sulfonylureas or insulin. 5
• If glycemic control is inadequate after 4–8 weeks at 50 mg weekly and the patient tolerates the medication well, consider increasing to 100 mg weekly. 5

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Timing and Administration

• Trelagliptin should be taken on the same day each week to maintain consistent drug levels and simplify adherence. 2
• If a dose is missed, take it as soon as remembered unless it is within 3 days of the next scheduled dose—in that case, skip the missed dose and resume the regular weekly schedule. 2
• Do not take two doses within 3 days of each other to avoid excessive DPP-4 inhibition and potential adverse effects. 2

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Monotherapy vs. Combination Therapy

• Trelagliptin 100 mg weekly can be used as monotherapy in patients inadequately controlled by diet and exercise alone, achieving mean HbA1c reductions of -0.74% over 52 weeks. 2
• It is also effective in combination with other oral antidiabetic agents, including:
  • Sulfonylureas (e.g., glipizide, glimepiride) 2
  • Biguanides (metformin) 2
  • Thiazolidinediones (pioglitazone) 2
  • α-glucosidase inhibitors (acarbose, miglitol) 2
  • Glinides (repaglinide, nateglinide) 2
• When combining trelagliptin with sulfonylureas or insulin, reduce the dose of the sulfonylurea or insulin by 20–30% to minimize hypoglycemia risk. 5, 2

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Dose Titration and Monitoring

• No dose titration is required for trelagliptin—patients remain on the same weekly dose (100 mg or 25 mg depending on renal function) throughout treatment. 1, 4
• Assess glycemic control (HbA1c and fasting plasma glucose) at 12–16 weeks after initiation to determine treatment efficacy. 1, 2
• If HbA1c remains above target after 3–6 months at the appropriate dose, add or intensify other glucose-lowering agents (e.g., metformin, SGLT2 inhibitors, GLP-1 receptor agonists) rather than increasing trelagliptin dose. 6, 2

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Special Populations

Elderly Patients

• No dose adjustment is needed based on age alone, but elderly patients with declining renal function should have creatinine clearance assessed and dose adjusted accordingly. 4, 3
• Monitor elderly patients more closely for hypoglycemia, especially if combined with sulfonylureas or insulin. 3

Hepatic Impairment

• No dose adjustment is required for patients with hepatic impairment, as trelagliptin is primarily eliminated renally. 3

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Safety and Tolerability

• Trelagliptin is well tolerated with a safety profile similar to daily DPP-4 inhibitors, with most adverse events being mild to moderate. 1, 3
• The most common adverse events include gastrointestinal complaints (abdominal pain, nausea, diarrhea) occurring in up to 16% of patients. 5, 2
• Hypoglycemia risk is minimal when used as monotherapy but increases when combined with sulfonylureas or insulin. 1, 3
• Body weight remains stable with trelagliptin—no significant weight gain or loss is observed. 5, 1

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Common Pitfalls to Avoid

• Do not use trelagliptin in patients with type 1 diabetes or diabetic ketoacidosis—it is only indicated for type 2 diabetes. 5
• Do not combine trelagliptin with other DPP-4 inhibitors (e.g., sitagliptin, linagliptin)—there is no additional benefit and it increases adverse event risk. 6
• Do not assume the 100 mg weekly dose is appropriate for all patients—always assess renal function and adjust to 25 mg weekly if creatinine clearance is <30 mL/min. 4
• Do not delay dose reduction of sulfonylureas or insulin when adding trelagliptin—failure to reduce these agents increases hypoglycemia risk. 5, 2

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Comparison to Daily DPP-4 Inhibitors

• Trelagliptin 100 mg once weekly is non-inferior to alogliptin 25 mg daily in terms of HbA1c reduction (mean difference 0.11%, 95% CI -0.054 to 0.281). 1
• The once-weekly dosing of trelagliptin offers improved convenience and potentially better adherence compared to daily DPP-4 inhibitors, without compromising efficacy or safety. 1, 3
• For patients with severe renal impairment, trelagliptin 25 mg weekly is more convenient than daily sitagliptin 25 mg (which also requires dose reduction in renal impairment). 5, 4