Clinical Significance of the Potential Amlodipine–Metformin Interaction: A Systematic Review

Abstract

Amlodipine and metformin are frequently co-administered in patients with hypertension and type 2 diabetes mellitus (T2DM). Although their concomitant use has been identified as a potential drug–drug interaction (pDDI), the clinical significance of this interaction remains uncertain. This systematic review aimed to evaluate the frequency, severity, proposed mechanism, and clinical significance of the potential interaction between amlodipine and metformin. A comprehensive literature search was conducted using PubMed, ScienceDirect and supplementary searches through Google Scholar with the keywords “amlodipine” AND “metformin” AND “drug interaction”. Study selection was conducted according to the PRISMA framework. Methodological quality was assessed using the appropriate Joanna Briggs Institute (JBI) Critical Appraisal Tools according to the design of each study. A total of 702 records were identified, 42 full-text articles were assessed for eligibility, and seven studies met the inclusion criteria and were included in the final narrative synthesis. Concomitant amlodipine and metformin use was consistently identified as a potential DDI, although the reported frequency varied across studies and was based on different reporting units, including patients, prescriptions, and total identified DDI events. The interaction was generally classified as moderate or requiring monitoring, with pharmacodynamic antagonism and a potential reduction in metformin effectiveness being the most frequently reported interaction profile. Current evidence demonstrates a recurring potential interaction signal between amlodipine and metformin but does not establish that concomitant use causes clinically meaningful deterioration in glycemic control