Serum magnesium and the effect of empagliflozin in heart failure

Magnesium (Mg2+), also known as “the forgotten ion,” is the second most abundant cation found in the body's cells (intracellular). Ions are molecules with an electrical charge, cations are ions with a positive (+) electrical charge. Mg2+ is essential in a broad range of intracellular physiological and biochemical reactions i.e., reactions that are essential to the normal functioning of the cells.
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More specifically, in the human body magnesium playes several roles, including making proteins, muscle and nerve function, blood glucose control, and blood pressure regulation.

A deficiency of Mg2+, called hypomagnesemia, is a prevalent condition and routinely poses challenges in its management in clinical practice, because it can lead to fatal arrhythmias (irregular heartbeat) and cause death.

Previous studies in patients with type 2 diabetes i.e., a condition where the blood sugar is elevated, suggested that sodium-glucose co-transporter 2 (SGLT2) inhibitors (a treatment that increases removal of glucose in the urine and thus lowers blood glucose) may increase Mg2+ levels in the blood as an additional benefit not related to its effect on blood sugar.

The effect of SGLT2 inhibitors on Mg2+ levels of patients with heart failure (HF) i.e., a condition characterized by a difficulty of the heart in pumping the blood to the whole body, has not been described yet.

The aims of this study in a large HF population, are to assess the prevalence of hypomagnesemia at baseline (before treatment with SLTG2 inhibitor), the associations of Mg2+ levels with cardiovascular outcomes, and the effect of the SGLT2 inhibitor empagliflozin on Mg2+ levels over time.

Beyond serum Mg2+, calcium (Ca2+), bicarbonate (HCO3-), phosphate (PO43-), sodium (Na+), and chloride (Cl-) are important ions for physiological and biochemical body functions. To date, the knowledge about the impact of SGLT2 inhibitors on these ions is very limited.

Some reports described a potential increase in serum calcium with SGLT2 inhibitors. Serum phosphate levels are also thought to be slightly increased with SGLT2 inhibitors. Some authors think that SGLT2 inhibitors may lead to a small decrease in serum bicarbonate, because of a decrease in reabsorption in the kidneys.
While SGLT2 inhibitors may cause transient natriuresis (short-term increase in sodium excretion via urine), their impact on serum sodium has been described as minimal. SGLT2 inhibitors may preserve or increase serum chloride.

Given the limited knowledge about the impact of SGLT2 inhibitors on these ions, particularly among patients with HF, there is a need to further explore how these ions associate with outcomes and how SGLT2 inhibitors impact them over time.