Treatment with metformin appears to be safe and efficacious in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) as long as the dose is adjusted for renal function, according to a study published in Diabetes Care.
Using an open-label single-center design, researchers conducted a dose-finding study with metformin in patients with CKD stage 1 to 5; a 4-month treatment study validating the optimal metformin dose as a function of CKD stages 3A, 3B, and 4; and a pharmacokinetic study after administration of a single dose of metformin in steady-state CKD 3A, 3B, or 4.
They found that the suggested daily adjusted doses of metformin in CKD stages 3A and 3B are 1.5 g (0.5 g every morning + 1 g every evening) and 1 g (0.5 g every morning + 0.5 g every evening), respectively.
In addition, the estimated glomerular filtration rate (eGFR) should be assessed every 6 months in patients with CKD stage 3 and metformin should be discontinued in patients likely to experience acute kidney injury due to severe disease.
Because high blood metformin concentrations are possibly associated with hyperlactatemia, lactate should be measured in fragile patients, and metformin should be discontinued in patients with a blood lactate concentration greater than 5 mmol/L.
In patients with a blood lactate concentration greater than 2.5 mmol/L, the measurement should be repeated soon afterward and metformin should be discontinued if there are 2 consecutive blood lactate concentrations greater than 2.5 mmol/L.
In the first study to provide a solid basis for continuing metformin treatment in this population, the investigators concluded that, “Our results support recent guidelines on metformin treatment in moderate-to-severe CKD and open the way for the initiation of metformin treatment in severe CKD, providing that the metformin dose is adjusted to the eGFR.”
Lalau JD, Kajbaf F, Bennis Y, Hurtel-Lemaire A, Belpaire F, De Broe ME. Metformin treatment in patients with type 2 diabetes and chronic kidney disease stages 3A, 3B, or 4 [published January 5, 2018]. Diabetes Care. doi:10.2337/dc17-2231