Does the use of proton pump inhibitors increase the risk of hypomagnesemia: An updated systematic review and meta-analysis

BACKGROUND: Proton pump inhibitors (PPIs) are commonly used in the treatment of acid-related diseases; however, the association between the use of PPIs and potential risk of hypomagnesemia is controversial. METHODS: In the present study, databases including PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the Cochrane Library, and 4 Chinese databases were searched since the inception until April 2018. Previous observational studies on the incidence of hypomagnesemia in individuals exposed to PPIs were included. RESULTS: This systematic review involved 15 studies including 129,347 participants, and the sample size varied from 52 to 95,205. Meta-analysis of 14 studies indicated that the use of PPIs increased the risk of hypomagnesemia [RR, 1.44, 95% CI, 1.13–1.76; I(2), 85.2%]. Subgroup analysis revealed that the use of PPI was not associated with the incidence of hypomagnesemia in outpatients [RR, 1.49; 95% CI, 0.83–2.14; I(2), 41.4%] and hospitalized patients [RR, 1.05; 95% CI, 0.81–1.29; I(2), 62.1%], respectively. The use of PPIs was not related to the risk of hypomagnesemia based on the cut-off values of 1.8 mg/dL [RR, 1.73; 95% CI, 0.87–2.58; I(2), 65.2%], 1.7 mg/dL [RR, 1.48; 95% CI, 0.90–2.06; I(2), 87.6%], and 1.6 mg/dL [RR, 0.98; 95% CI, 0.69–1.27; I(2), 67.9%]. CONCLUSION: The association between the exposure to PPI and the incidence of hypomagnesemia remained unclear. Due to the remarkable heterogeneity in previous studies, a definitive conclusion could not be drawn. Further research should be conducted to investigate the relationship between the use of individual PPI and potential risk of hypomagnesemia, and a dose-response analysis may be required.