Efficacy and safety of trelagliptin in Japanese patients with type 2 diabetes with severe renal impairment or end‐stage renal disease: Results from a randomized, phase 3 study

Abstract

Introduction To investigate the efficacy and safety of trelagliptin 25 mg in patients with type 2 diabetes mellitus with severe renal impairment or end‐stage renal disease. Materials and Methods This multicenter, randomized, phase 3 study comprised a 12‐week double‐blind phase followed by a 40‐week open‐label phase. Patients had type 2 diabetes mellitus with severe renal impairment (creatinine clearance <30 mL/min) or end‐stage renal disease (undergoing hemodialysis), and were receiving diet and/or exercise therapy with/without one antidiabetic drug. Results Patients were randomized to trelagliptin (A/A, n = 55) or placebo (P/A, n = 52; double‐blind phase). Both groups received trelagliptin in the open‐label phase. The least square mean change (95% confidence interval [CI]) from baseline in hemoglobin A1c at the end of the double‐blind phase was −0.71% (95% CI −0.885, −0.542) and 0.01% (95% CI −0.170, 0.183) in the A/A and P/A groups, respectively (intergroup least square means difference −0.72%, 95% CI −0.966, −0.473; P < 0.0001). Mean hemoglobin A1c decreased after trelagliptin treatment in the P/A group to similar levels observed in the A/A group and remained comparable in both groups versus baseline up to week 52. In the double‐blind phase, the incidence of treatment‐emergent adverse events (TEAEs) was 72.7% and 61.5% in the A/A and P/A group, respectively; most TEAEs were mild‐to‐moderate, except in one patient (P/A group), who experienced two severe TEAEs. The incidence of serious TEAEs was 7.3% and 3.8% in the A/A and P/A group, respectively. Conclusions Once‐weekly trelagliptin 25 mg was efficacious, with no major safety concerns, and represents a meaningful treatment option in this patient population.

Impact of Reduction in Pill Load Upon Use of a Once Weekly DPP-4 Inhibitor in 2 Cases of Type 2 Diabetes

“…It conforms to the characteristics of other DPP-4 inhibitors in the increased safety profile against hypoglycemic events in comparison to sulphonyl urea's (except gliclazide), which have made the class an exceedingly popular solution to Diabetes mellitus type 2 [5]. Even with severe renal impairment of CrCl <30, trelagliptin has shown no major safety concerns in a study after adjusting the dose to 25mg once a week [6].…”

Toward Revision of the ‘Best Practice for Diabetic Patients on Hemodialysis 2012’

“…On the other hand, linagliptin and teneligliptin can be administered without dose adjustment, even in patients on dialysis. Furthermore, the once-weekly DPP-4 inhibitors, omarigliptin and trelagliptin, are also available with dose adjustment for patients on dialysis [76,77]. However, further studies are needed to clarify the efficacy and safety of these agents, since few reports have investigated the efficacy and safety of once-weekly DPP-4 inhibitors for dialysis patients.…”

New prospects for incretin‐related drugs in the treatment of type 2 diabetes

“…In addition, safety in administration to the elderly has been established 4 . DPP‐4 inhibitors can be safely and effectively used, even in end‐stage renal disease with appropriate dose reduction 5 , the exceptions being linagliptin and teneligliptin, which can be freely used due to its non‐renal clearance. Currently, two once‐weekly DPP‐4 inhibitors – trelagliptin and omarigliptin – are available mainly in Japan and several Asian countries.…”