SGLT2 Inhibitors, GLP-1 RAs, and DPP-4 Inhibitors: Hypomagnesemia Risk in Type 2 Diabetes

06 Mar 20264 min read0 viewsJournal Feed

GIST

by Shih-Chieh Shao, Daniel Hsiang-Te Tsai, Albert Tzu-Ming Chuang, Kuan-Hung Liu, Edward Chia-Cheng Lai Background Recent studies have suggested potential effects on magnesium homeostasis associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We sought to determine whether these effects lead to a reduced risk of hypomagnesemia among adults with type 2 diabetes in clinical practice.

Methods and findings We conducted a target trial emulation study using the multi-institutional cohort data from the TriNetX Global Collaborative Network. We compared 1:1 propensity score-matched patients with type 2 diabetes newly initiating SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors ( n = 718,798), GLP-1 RAs versus DPP4 inhibitors ( n = 623,390), and SGLT2 inhibitors versus GLP-1 RAs ( n = 702,808) from 2016 to 2024.

Propensity scores were estimated using logistic regression models that included baseline covariates such as age, sex, race, comorbidities, and medication and laboratory data. In each comparison, patients receiving DPP4 inhibitors were considered the active-comparator group.

Clinical Editorial

Hypothesis and Study Intent

Contextual aim: To assess whether initiation of SGLT2 inhibitors or GLP-1 receptor agonists (GLP-1 RAs) in adults with type 2 diabetes is associated with a reduced risk of hypomagnesemia in real-world practice, in comparison with DPP-4 inhibitors.

Design and Data Context

Methodological approach: A target trial emulation using multi-institutional TriNetX Global Collaborative Network data.
Population and matching: Three head-to-head comparisons with 1:1 propensity score matching, balancing baseline characteristics via logistic regression that included demographics, comorbidities, medications, and laboratory data.
Comparisons and sample sizes:
SGLT2 inhibitors versus DPP-4 inhibitors (n = 718,798).
GLP-1 RAs versus DPP-4 inhibitors (n = 623,390).
SGLT2 inhibitors versus GLP-1 RAs (n = 702,808).
Time frame: Data spanning 2016 through 2024.
Active comparator: DPP-4 inhibitors in each analysis.

Exposure and Outcome Definition

Exposure of interest: Initiation of SGLT2 inhibitors or GLP-1 RAs.
Primary outcome: Incident hypomagnesemia, defined by either clinical diagnosis or serum magnesium measurement abnormality, as recorded in the data source.

Key Findings and Interpretation

Main result: Treatment with SGLT2 inhibitors and GLP-1 RAs was associated with a lower risk of hypomagnesemia when each was compared with DPP-4 inhibitors.
Contextual interpretation: The findings imply potential magnesium-sparing effects for these agents relative to DPP-4 inhibitors in routine clinical practice.