Objective: To map the relation between metformin prescription and renal function in an outpatient setting. To investigate whether there is an association between renal function, metformin concentration and lactate concentration.
Design: Pilot for a prospective observational cohort study.
Method: We included outpatients with diabetes mellitus type 2 who were treated with metformin. At inclusion, we determined the HbA1c, lactate, metformin and creatinine concentrations and the estimated glomerular filtration rate (eGFR). Information on the prescribed dosage of metformin was acquired from patient files. Our primary outcome measure was the number of patients in whom the dose was not adjusted to the renal function. Our secondary outcome measure was the difference in median lactate concentration between patients with a normal (≤ 2.5 mg/l) and an increased (> 2.5 mg/l) metformin concentration.
Results: Eighty-eight patients were included, 12 (14%) of whom had an eGFR ≤ 30, 31 (36%) an eGFR of 30-50 and 44 (50%) an eGFR > 51 ml/min/1.73 m2. In 27 (31%) of all patients, the daily dose of metformin exceeded the dose recommended in the practice guidelines. The 28 patients with an increased metformin concentration had a significantly higher median lactate concentration: 2.3 mmol/l compared to 1.5 mmol/l for the 60 patients with a normal metformin concentration (p < 0.0001).
Conclusion: Our study shows that in outpatient practice, the metformin dose is not sufficiently adjusted to a reduced renal function in 31% of the patients. The accumulation of metformin appears to be associated with an increased lactate concentration and a reduced renal function. Extra attention to the dose of metformin in reduced renal clearance is therefore recommended.