title: Proton pump inhibitors do not impair the effectiveness of metformin in patients with diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Division of Endocrinology, Weill Cornell Medical College, New York, NY.
authors.forename: James
authors.initials: J
authors.lastname: Flory
authors.forename: Kevin
authors.initials: K
authors.lastname: Haynes
authors.forename: Charles E
authors.initials: CE
authors.lastname: Leonard
authors.forename: Sean
authors.initials: S
authors.lastname: Hennessy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D012189:Retrospective Studies; D000099254:Organic Cation Transporter 3
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D054328:Proton Pump Inhibitors; D000099254:Organic Cation Transporter 3; C491013:SLC22A2 protein, human
keywords: HbA1c; diabetes; drug-drug interaction; glucose; metformin; proton pump inhibitor