Proton pump inhibitors do not impair the effectiveness of metformin in patients with diabetes

Aims In order to exert its pharmacodynamic effect, the diabetes drug metformin needs to be taken up into hepatocytes by the organic cation transporter ( OCT ) system. A recent in vitro study found that proton pump inhibitors ( PPIs ) inhibit OCT1 , OCT2 and OCT3 , suggesting that PPIs might reduce metformin's effectiveness. This pharmacoepidemiologic study looked for evidence of a clinical effect of such an interaction. Methods This was an observational cohort study examining changes in glycosylated haemoglobin ( HbA1c ) with exposure to metformin and to PPIs as single agents and in combination. The aim was to assess evidence of a deleterious drug−drug interaction. Results PPIs did not reduce the effectiveness of metformin, and indeed were associated with a minimally better glycaemic response by − 0.06 HbA1c percentage points (95% confidence interval, −0.10, −0.01) in metformin initiators. Conclusions Despite a mechanistic basis for a potential drug–drug interaction, we found no evidence of a deleterious interaction between PPIs and metformin.