Metformin use in patients with renal impairment requires monitoring due to potential lactic acidosis risk. A single-arm design study published in the Journal of Diabetes Investigation evaluated the safety of a fixed-dose anagliptin/metformin combination by assessing serum lactic acid levels in Japanese patients with type 2 diabetes and moderate renal dysfunction.

Patients with estimated glomerular filtration rate based on creatinine (eGFRcr) ≥45 and <60 mL/min/1.73 m² (Group G3a) received low-dose (LD) tablets (anagliptin 100 mg, metformin 250 mg per tablet) twice daily for 4 weeks, followed by high-dose (HD) tablets (anagliptin 100 mg, metformin 500 mg per tablet) twice daily through week 16. Patients with eGFRcr ≥30 and <45 mL/min/1.73 m² (Group G3b) received LD tablets twice daily for 16 weeks. Serum lactic acid was measured at weeks 4, 8, and 16.

The mean change in lactic acid from baseline to week 16 was −0.09 mmol/L (95% CI −0.28 to 0.10), not exceeding the prespecified noninferiority margin of 0.7 mmol/L. No significant changes occurred across observation periods. Lactic acid levels exceeded 2.5 mmol/L in four participants (10.5%) and 5.0 mmol/L in one participant (2.6%). No participant had plasma metformin levels above 2.5 μg/mL.

In this single-arm study of Japanese patients with type 2 diabetes and moderate renal impairment, anagliptin/metformin combination therapy did not result in clinically meaningful increases in serum lactic acid over 16 weeks. Observed changes remained within the prespecified noninferiority margin, and no plasma metformin levels exceeded the defined safety threshold.

Limitations included single-arm design, small sample size, 16-week follow-up, demographic imbalance, and restriction to Japanese participants.

In Japanese patients with type 2 diabetes and moderate renal impairment, anagliptin/metformin therapy did not increase mean lactic acid levels over 16 weeks, remaining within the prespecified noninferiority margin.