Metformin in peritoneal dialysis: a pilot experience

Abstract

Objective: In a number of patients, the antidiabetic drug metformin has been associated with lactic acidosis. Despite the fact that diabetes mellitus is the most common cause of end-stage renal disease (ESRD) and that peritoneal dialysis (PD) is an expanding modality of treatment, little is known about optimal treatment strategies in the large group of PD patients with diabetes. In patients with ESRD, the use of metformin has been limited because of the perceived risk of lactic acidosis or severe hypoglycemia. However, metformin use is likely to be beneficial, and PD might itself be a safeguard against the alleged complications.

Methods: Our study involved 35 patients with insulin-dependent type 2 diabetes [median age: 54 years; interquartile range (IQR): 47-59 years] on automated PD (APD) therapy. Patients with additional risk factors for lactic acidosis were excluded. Metformin was introduced at a daily dose in the range 0.5 - 1.0 g. All patients were monitored for glycemic control by blood sugar levels and HbA1c. Plasma lactic acid levels were measured weekly for 4 weeks and then monthly to the end of the study. Plasma and effluent metformin and plasma lactate levels were measured simultaneously.

Results: In this cohort, the median duration of diabetes was 18 years (IQR: 14 - 21 years), median time on PD was 31 months (IQR: 27 - 36 months), and median HbA1c was 6.8% (IQR: 5.9% - 6.9%). At metformin introduction and at the end of the study, the median anion gap was 11 mmol/L (IQR: 9 - 16 mmol/L) and 12 mmol/L (IQR: 9 - 16 mmol/L; p > 0.05) respectively, median pH was 7.33 (IQR: 7.32 - 7.36) and 7.34 (IQR: 7.32 - 7.36, p > 0.05) respectively, and mean metformin concentration in plasma and peritoneal fluid was 2.57 ± 1.49 mg/L and 2.83 ± 1.7 mg/L respectively. In the group overall, mean lactate was 1.39 ± 0.61 mmol/L, and hyperlactemia (>2 mmol/L to 5 mmol/L) was found in 4 of 525 plasma samples (0.76%), but the patients presented no symptoms. None of the patients registered a plasma lactate level above 5 mmol/L. We observed no correlation between plasma metformin and plasma lactate (r = 0.27).

Conclusions: Metformin may be used with caution in APD patients with insulin-dependent type 2 diabetes. Although our study demonstrated the feasibility of metformin use in APD, it was not large enough to demonstrate safety; a large-scale study is needed.

Keywords: BMI; ESRD; Metformin; acidosis; hypoglycemia; lactic acid.

Figure 1 —

Consort diagram demonstrating study design. CHF = chronic heart failure; CRD = chronic respiratory disease; CLD = chronic liver disease, LA = serum lactic acid.

Figure 2 —

Median (A) serum pH and (B) anion gap in relation to study duration. Q1 = quartile 1; Q3 = quartile 3.

Figure 3 —

Relationship between plasma lactate and plasma metformin in the study patients, r = 0.27 (nonsignificant).