Nonprescription Magnesium Supplement Use and Risk of Heart Failure in Patients With Diabetes: A Target Trial Emulation.

Background: Both diabetes and low magnesium-containing food intake may increase the risk of heart failure (HF). However, the effect of nonprescription magnesium supplements on the risk of HF or major adverse cardiac events in patients with diabetes is unknown.

Methods and results: Using a target-trial-emulation approach, we assembled a national cohort of 94 239 veterans ≥40 years with diabetes, without prior HF or magnesium use, who received ambulatory care in the US veterans-health care system documented by electronic clinic notes between January 1, 2006 and December 31, 2020. A natural language processing approach was used to detect self-reported magnesium-supplement use from clinic notes, n=17 619 were identified as users versus n=76 620 as nonusers. Using inverse probability treatment weighting, we constructed a cohort balanced in 88 baseline characteristics between users and nonusers. The primary outcome was incident HF. Secondary outcomes were major adverse cardiac events (myocardial infarction, stroke, HF hospitalization, or death). Hazard ratios (HRs) associated with magnesium-supplement use and outcomes were estimated in the inverse probability treatment weighting weighted cohort using Cox regression. The inverse probability treatment weighting weighted cohort had a mean age of 67.4±10.3 years; 18.4% were Black, and 5.1% were women. The mean duration of magnesium-supplement use was 3.5±3.1 (interquartile range, 1.1-5.1) years. Incident HF occurred in 8.0% of users and 9.7% of nonusers of magnesium supplements (HR, 0.94 [95% CI, 0.89-0.99]). Magnesium-supplement use was also associated with a reduced risk of major adverse cardiac events (HR, 0.94 [95% CI, 0.90-0.97]).

Conclusions: Long-term nonprescription magnesium supplement use was associated with a lower risk of incident HF and major adverse cardiac events in patients with diabetes. These findings should be replicated in randomized controlled trials.