Ria Andani Antong, Ikhwan Yuda Kusuma, Marianti A. Manggau, Muh Akbar Bahar
Metformin, a substrate of the organic cation transporters, is commonly co-prescribed with proton pump inhibitors, which inhibits these transporters. However, the clinical significance of this potential drug-drug interaction remains unclear. This systematic review aimed to assess the potential and clinical relevance of the interaction between proton pump inhibitors and metformin based on published clinical evidence. PubMed and Embase were searched for studies reporting the effects of this interaction in adults (≥18 years old), published up to January 2024. Data on pharmacokinetic and pharmacodynamic effects were collected and analyzed. The study protocol is registered in PROSPERO (CRD42023456957). A total of 14 studies were included, comprising five experimental and nine observational studies. Experimental pharmacokinetic studies indicated minimal changes in metformin AUC when combined with proton pump inhibitors, with reported changes ranging from a slight decrease (-5.46%) to a moderate increase (up to +17%). Pharmacodynamic data from both experimental and observational studies supported these findings, showing minimal clinically relevant changes in HbA1c levels. However, some studies reported decreased vitamin B12 levels in patients with type 2 diabetes mellitus using both proton pump inhibitors and metformin. Based on the current clinical evidence, the impact of drug-drug interaction between proton pump inhibitors and metformin is minimal. However, regular monitoring of glucose and vitamin B12 levels is advised for high-risk populations and those on long-term metformin and proton pump inhibitor therapy. © (2025), (Pensoft Publishers). All rights reserved.
Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia; Pharmacy Study Program, Faculty of Health, Universitas Harapan Bangsa, Purwokerto, 53182, Indonesia; Department of Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia
Research at a Glance
Register to unlock
Topics & SDG Alignment
Register to unlock
Collaboration
Register to unlock
Author Profile (Selected)
Register to unlock
References Overview
Register to unlock
Journal & Source
Register to unlock
Metadata & Integrity
Register to unlock