Metformin treatment in NIDDM patients with mild renal impairment

Abstract

Metformin is contraindicated in patients with renal failure because of the risk of lactic acidosis. This study assessed the complications of metformin treatment in patients with non-insulin-dependent diabetes mellitis with normal and raised serum creatinine. Subjects using metformin with serum creatinine above the upper reference range (120 mu mol/l) were identified (n = 17) from a hospital diabetes register; those with abnormal liver function, cardiac failure, peripheral vascular disease or recent severe illness were excluded. Reference plasma lactate levels were established, mean 1.742 mu mol/l (SD 0.819) using age-matched non-diabetic subjects. Age-matched patients treated with metformin with normal serum creatinine levels formed the control group (n = 24). Details of gastrointestinal disturbance were recorded, and plasma lactic acid and vitamin B12 levels measured. The median total daily dose of metformin in both groups was 1700 mg. The mean plasma lactate in subjects with serum creatinine 80-120 mu mol/l (2.640 mmol/l (SD 1.434) p < 0.02) was higher than non-diabetic control levels while diabetic subjects with serum creatinine 120-160 mumol/l had a mean of 2.272 mmol/l (SD 0.763) p < 0.05. There was no significant difference between the two groups taking metformin, nor any significant difference in the reporting of gastrointestinal symptoms between the groups on metformin (11.76% vs 12.5%). Plasma lactic acid levels are higher in diabetic subjects taking metformin compared with healthy volunteers but, within the diabetic groups, the small elevation of serum creatinine was not associated with higher plasma lactate levels.