A comprehensive review on potential drug–drug interactions of proton pump inhibitors with antidiabetic drugs metformin and DPP‐4 inhibitors

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP‐4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP‐4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug–drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP‐4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP‐4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP‐4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP‐4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis. Significance statement This review highlights that metformin and DPP‐4 inhibitors often cause gastrointestinal side effects, leading to the coadministration of proton pump inhibitors (PPIs). It systematically explores potential drug–drug interactions of PPIs with metformin and DPP‐4 inhibitors, revealing impacts on absorption, metabolism, and antidiabetic activity. The paper emphasizes the need for careful dose control when prescribing these drugs concurrently, aiming for optimal therapeutic impact with minimal side effects. With a lack of prior research on this topic, the article suggests a potential avenue for extensive in vitro, in vivo, and human studies to confirm the drug interactions, providing valuable insights for drug prescribers and researchers in diabetes management.