• Willemijn L Eppenga, Arief Lalmohamed, Arjen F Geerts, Hieronymus J Derijks, Michel Wensing, Antoine Egberts, Peter A G M De Smet, and Frank de Vries.
• Scientific Institute for Quality of Healthcare, Radboud University Nijmegen Medical Center, Nijmegen, the NetherlandsHospital Pharmacy 'ZANOB', 's-Hertogenbosch, the Netherlands.
• Diabetes Care. 2014 Aug 1;37(8):2218-24.

ObjectiveThe objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin.Research Design And MethodsA cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD).The primary outcome was defined as either a CPRD READ code lactic acidosis or a record of a plasma lactate concentration >5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs).ResultsThe crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function <60 mL/min/1.73 m(2) (adjusted HR 6.37 [95% CI 1.48-27.5]). The increased risk among patients with impaired renal function was further increased in users of ≥730 g of metformin in the preceding year (adjusted HR 11.8 [95% CI 2.27-61.5]) and in users of a recent high daily dose (>2 g) of metformin (adjusted HR 13.0 [95% CI 2.36-72.0]).ConclusionsOur study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m(2).© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

33 keywords...

hide…