Effects of Canagliflozin (CANA) on Serum Magnesium (Mg) in Patients With Type 2 Diabetes Mellitus (T2DM)

Abstract

Hypomagnesemia is an established risk factor for ventricular arrhythmia that is also associated with T2DM and its cardiometabolic complications. CANA, an SGLT2 inhibitor, has been shown to increase serum Mg without detectable changes in fractional excretion in patients with T2DM. We evaluated the proportion of patients with low serum Mg (<1.8 mg/dL) at baseline (BL) and week 26 using pooled data from 4 placebo (PBO) controlled studies of CANA in 2313 patients with T2DM (mean serum Mg=1.9 mg/dL; range=1 to 3 mg/dL). At BL, 18.3% of patients had Mg <1.8 mg/dL, 80.7% had Mg 1.8 to 2.3 mg/dL (normal Mg), and 1.0% had Mg >2.3 mg/dL (hypermagnesemia). Patients with Mg <1.8 mg/dL were more likely to be female, white, have longer T2DM duration and have microvascular disease than those with Mg ≥1.8 mg/dL. At week 26, increases in serum Mg were seen with CANA 100 and 300 mg vs. PBO in patients with BL Mg <1.8 mg/dL (17.0% and 19.0% vs. 3.9%) and Mg ≥1.8 mg/dL (4.9% and 7.0% vs. –1.4%). A greater proportion of patients with BL Mg <1.8 mg/dL had Mg ≥1.8 mg/dL at week 26 with CANA 100 and 300 mg vs. PBO (74.1% and 80.6% vs. 28.8%; Figure). Hypomagnesemic patients treated with CANA vs. PBO were 10 to 14 times more likely to achieve Mg ≥1.8 mg/dL. In summary, CANA treatment was associated with normalization of serum Mg in hypomagnesemic patients with T2DM, potentially leading to improved cardiometabolic outcomes and reduced risk of arrhythmia.