Metformin interferes with urinary creatinine measurement using enzymatic method

Abnormal reaction curves were observed in urinary creatinine tests in patients with diabetes undergoing metformin therapy. Therefore, we investigated whether metformin interferes with urinary creatinine measurements. First, the reaction curves of urinary creatinine measurements from 328 patients were analyzed, focusing on the maximum reaction speed, final reaction speed, and their ratio. Next, the reaction curves of the creatinine solution with and without metformin were analyzed. To elucidate the mechanism of metformin interference, solutions of creatinine, creatine, sarcosine, and hydrogen peroxide with and without metformin were analyzed using a one-reagent measurement in which reagents 1 and 2 were pre-mixed. As the results, in the 84 patients taking metformin, the maximum reaction speed significantly decreased, whereas the final reaction speed and the ratio of the two speeds significantly increased (p < 0.001). Notably, the area under the curve of the ratio of the two speeds was 0.84 (95 % confidence interval: 0.78-0.89) for detecting metformin use, suggesting that metformin inhibits the series of reactions involved in creatinine measurement and that reaction curve analysis can identify metformin use. Similar results were obtained in experiments using metformin-containing creatinine solutions. Metformin did not interfere with the reactions involving sarcosine or hydrogen peroxide but did interfere with those involving creatinine and creatine, indicating that metformin inhibits creatinase activity. In conclusion, metformin inhibits reactions involved in urinary creatinine measurement in urine samples, potentially leading to falsely low urinary creatinine values and an inaccurate assessment of kidney function in patients with diabetes.