title: 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.
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Abdulla Khalaf
authors.initials: AK
authors.lastname: Al-Hwiesh
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ibrahiem Saeed
authors.initials: IS
authors.lastname: Abdul-Rahman
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mohammad Ahmad Nasr
authors.initials: MA
authors.lastname: El-Deen
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Larbi
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Divino-Filho
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Fahd Abdul-Aziz
authors.initials: FA
authors.lastname: Al-Mohanna
authors.affiliation: Department of Internal Medicine, King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology, University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Krishan L
authors.initials: KL
authors.lastname: Gupta
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced / Q000517:prevention & control; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000379:methods*; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: BMI; ESRD; Metformin; acidosis; hypoglycemia; lactic acid