Long-Term Safety and Effectiveness of Linagliptin in Japanese Patients with Type 2 Diabetes and Renal Dysfunction: a Post-Marketing Surveillance Study

Introduction International clinical trials have shown that linagliptin significantly improves glycemic control and can be used at a single dose regardless of renal function in patients with type 2 diabetes (T2D). However, to date, no studies have evaluated the use of linagliptin in Japanese patients with T2D by renal function in routine clinical care. Methods This was a subgroup analysis of data from a prospective observational post-marketing surveillance (PMS) study of linagliptin conducted in Japan that evaluated the safety and effectiveness of linagliptin in routine clinical care for 3 years in Japanese patients with T2D. The subgroup analysis examined the patient population of this PMS study according to renal function using estimated glomerular filtration rate (eGFR) data. The incidence of linagliptin-related adverse events (adverse drug reactions [ADRs]) was the primary endpoint, and the change in glycated hemoglobin (HbA1c) from baseline to last observation was the secondary endpoint. Results Of the 2235 patients included in the safety analysis, eGFR was ≥ 90 mL/min/1.73 m 2 (defined as group G1) in 16.9% ( n = 377), ≥ 60 to < 90 mL/min/1.73 m 2 (group G2) in 44.5% ( n = 995), ≥ 30 to < 60 mL/min/1.73 m 2 (group G3) in 21.7% ( n = 486), ≥ 15 to < 30 mL/min/1.73 m 2 (group G4) in 2.6% ( n = 58) and < 15 mL/min/1.73 m 2 (group G5) in 1.7% ( n = 37). No eGFR data were available for 12.6% ( n = 282) of patients. In these GFR groups, the incidence of ADRs with linagliptin was 6.9% in group G1, 11.1% in group G2, 13.8% in group G3, 15.5% in group G4 and 16.2% in group G5; the change in HbA1c from baseline to the last observation was − 1.11, − 0.64, − 0.35, − 0.46 and − 0.54% in the respective subgroups. Conclusions Long-term linagliptin use showed sustained improvements in glycemic control with no new safety concerns regardless of renal function. Trial Registration ClinicalTrials.gov (NCT01650259). Funding This study was funded by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan K.K.