Serum Magnesium, Prescribed Magnesium Replacement and Cardiovascular Events in Adults with Type 2 Diabetes: A National Cohort Study in U.S. Veterans

Objectives: To investigate the relationship between serum magnesium levels, prescribed oral magnesium replacement, and major adverse cardiovascular events (MACE) in type-2 diabetes mellitus (T2D). Research design and methods: This nationwide retrospective study analyzed 1,284,940 US Veterans (≥18 years) with T2D who had outpatient serum magnesium testing between 1999–2021 in the Veterans Health Administration. The relationship between serum magnesium levels and MACE (hospitalizations for acute myocardial infarction, heart failure, ischemic stroke, or all-cause mortality) was determined using multivariable-adjusted Cox-regression models. Using a new-user-design and propensity-score-matching approach, we further related the use of prescribed oral magnesium and MACE among patients with hypomagnesemia (serum magnesium <1.8 mg/dL) and normomagnesemia (serum magnesium 1.8–2.3 mg/dL). Results: Of 1,284,940 patients with T2D, 229,210 (17.8%) patients had hypomagnesemia, and 117,674 (9.2%) patients had hypermagnesemia (serum magnesium >2.3 mg/dL). Compared to patients with normomagnesemia (serum magnesium 1.8–2.3 mg/dL), those with either hypomagnesemia or hypermagnesemia had elevated hazards for MACE. The risk increased with the severity of serum magnesium abnormalities in both directions—low (hazard ratios [HRs] 1.11–1.20) and high (HRs 1.04–1.39)—in a parabolic pattern. Oral magnesium was prescribed to 9.7% and 0.7% of patients with hypomagnesemia and normomagnesemia, respectively. After propensity-score-matching balanced across 64 baseline characteristics, oral magnesium was associated with a lower MACE risk in 40,766 matched patients with hypomagnesemia (HR 0.89; 95% confidence interval [CI], 0.84–0.93), especially those on proton-pump-inhibitors or thiazides. Oral magnesium was not related to MACE in 11,838 matched patients with normomagnesemia (HR 1.07; 95% CI, 0.97–1.17). Conclusions: In patients with T2D, both hypomagnesemia and hypermagnesemia were associated with higher one-year MACE risks compared to normomagnesemia. Prescribed oral magnesium was associated with a reduced MACE risk in hypomagnesemia but not in normomagnesemia.