ABSTRACT Aims/Introduction To investigate the safety of anagliptin/metformin combination tablets by evaluation of lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment. Materials and Methods The participants of type 2 diabetes with creatinine‐based eGFR (eGFRcr) of ≥45 and <60 (mL/min/1.73 m 2 ) (Group G3a) received anagliptin/metformin combination LD tablets (anagliptin: 100 mg, metformin hydrochloride: 250 mg/tablet) twice a day for 4 weeks. After 4 weeks, they received anagliptin/metformin combination HD tablets (anagliptin: 100 mg, metformin hydrochloride: 500 mg/tablet) twice daily until after 16 weeks. The participants (Group G3b) with baseline eGFRcr ≥30 and <45 (mL/min/1.73 m 2 ) received anagliptin/metformin combination LD tablets twice daily for 16 weeks. The serum lactic acid levels were examined at weeks 4, 8, and 16 after receiving anagliptin/metformin combination tablets. Results The change in serum lactic acid levels from baseline to 16 weeks was −0.09 −0.28, 0.10 mmol/L (mean 95% confidence intervals), not exceeding the pre‐specified non‐inferiority margin (0.7 mmol/L). No significant differences occurred in the change in serum lactic acid levels during all observation periods. Serum lactic acid levels exceeded 2.5 mmol/L in four participants (10.5%) and 5.0 mmol/L in one participant (2.6%) during the observation period. No participant had a plasma metformin exceeding 2.5 μg/mL. Conclusions This study demonstrates that the fixed‐dose combination of anagliptin and metformin can be used safely in patients with type 2 diabetes complicated by moderate renal dysfunction. The advantage of this fixed‐dose combination is also considered to be very large.
Kajio et al. (Thu,) studied this question.