Long‐term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes and chronic kidney disease: A 52‐week postmarketing clinical study (TWINKLE)

Aim To evaluate the long‐term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD). Materials and Methods This open‐label, single‐arm, multicenter, phase 4 study (TWINKLE) enrolled individuals with T2D and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 , treated with ≤1 oral hypoglycemic agent. Participants received 500 mg of imeglimin twice daily if eGFR was 15 to <45 mL/min/1.73 m 2 or 500 mg once daily if eGFR was <15 mL/min/1.73 m 2 , as monotherapy or in combination with their existing hypoglycemic agent, for 52 weeks. Dose adjustments were permitted based on safety and eGFR. Results Among 60 participants (CKD stages: G3b: n = 42; G4: n = 16; G5: n = 2), adverse events (AEs) occurred in 41 participants (68.3%), with no increased incidence across CKD stages. The most common AE was diarrhea ( n = 6, 10.0%). Baseline mean (SD) HbA1c, glycated albumin (GA), and fasting plasma glucose (FPG) levels were 7.59% (0.68%), 22.53% (3.27%), and 151.8 (28.86) mg/dL, respectively. At week 24, mean (SD) changes from baseline were −0.53% (0.51%) for HbA1c, −2.37% (2.08%) for GA, and −13.6 (20.87) mg/dL for FPG. At week 52 (last observation carried forward [LOCF]), mean changes were −0.26% (0.88%), −1.59% (3.04%), and −7.0 (31.17) mg/dL. The proportion achieving HbA1c < 7.0% increased from 13.3% at baseline to 50.0% at week 52 (LOCF). Conclusions This study confirmed the favorable safety profile and sustained glycemic efficacy of imeglimin in Japanese individuals with T2D and CKD stages G3b–5, supporting its use with dose adjustment in this population.