July 18, 2019
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SGLT2 inhibitors may address magnesium deficiency

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An add-on benefit of SGLT2 inhibitors in the treatment of type 2 diabetes may be improving magnesium levels, according to findings published in the Journal of Diabetes and its Complications.

“In patients with [type 2 diabetes], hypomagnesemia may contribute to a worsening of insulin resistance, which can then further reduce serum [magnesium] concentrations,” Robert D. Toto, MD, associate dean of translational science and professor at the University of Texas Southwestern Medical Center in Dallas, and colleagues wrote. “Recent evidence suggests that SGLT2 [inhibitor] treatment, either alone or in combination with other agents, corrects low serum [magnesium] concentrations in patients with [type 2 diabetes], potentially contributing to improved cardiometabolic outcomes.”

Toto and colleagues conducted a post hoc analysis of 10 placebo-controlled trials with dapagliflozin (Farxiga, AstraZeneca) as the medication of interest. The dose of dapagliflozin was 10 mg per day in each study, with the researchers focused on 24 weeks of results and magnesium levels reached compared with baseline. Magnesium was measured from blood samples that were taken every 4 weeks.

Of the 4,398 adults with type 2 diabetes in the combined studies, 773 had a serum magnesium level of less than 0.74 mmol/L, which the researchers classified as hypomagnesemia, at baseline. Among this cohort, 403 were randomly assigned to dapagliflozin therapy (mean age, 60.8 years; 46.7% women), and 370 were assigned to placebo (mean age, 61.2 years; 49.2% women). The remaining participants (n = 3,625) were randomly assigned to dapagliflozin (n = 1,831; mean age, 58 years; 41.9% women) or placebo (n = 1,794; mean age, 48.7 years; 40.6% women).

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An add-on benefit of SGLT2 inhibitors in the treatment of type 2 diabetes may be improving magnesium levels.
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The average magnesium level in participants who took dapagliflozin was 0.81 mmol/L at baseline and 0.86 mmol/L after 24 weeks whereas those taking placebo went from 0.81 mmol/L at baseline to 0.8 mmol/L at the end of the study, which made for a 0.06 mmol/L (95% CI, 0.05-0.06) variation between each group, according to the researchers.

The results were greater for those with hypomagnesemia who took dapagliflozin (0.66 mmol/L at baseline to 0.77 mmol/L at 24 weeks) compared with those in the placebo group with similar baseline magnesium measures (0.66 mmol/L at baseline to 0.69 mmol/L at 24 weeks). This yielded a 0.08 mmol/L disparity in magnesium adjustment (95% CI, 0.07-0.09), according to the researchers.

Among those with magnesium levels of at least 0.74 mmol/L, the average baseline measure of magnesium was 0.84 mmol/L regardless of treatment, but those taking dapagliflozin experienced an increase during the studies (0.87 mmol/L) and those on placebo experienced a decrease (0.82 mmol/L), making for a 0.05 mmol/L (95% CI, 0.05-0.06) difference in magnesium alteration between the two groups, the researchers noted.

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In total, 77.3% of those who took dapagliflozin reached a serum magnesium level of at least 0.74 mmol/L whereas 29.5% of those taking a placebo reached the threshold, allowing the researchers to calculate a 47.8% gap between the two groups (95% CI, 41.4-53.9).

Similar rates of adverse events were observed in those taking dapagliflozin vs. those taking placebo, according to the researchers, who also noted that dapagliflozin decreased blood pressure and heart rate measures more effectively than placebo.

“Treatment with dapagliflozin 10 mg resulted in correction of serum [magnesium] concentration in patients with [type 2 diabetes] and hypomagnesemia, without increased risk for hypermagnesemia,” the researchers wrote. “Whether the reduction in the risk of cardiovascular and renal events induced by SGLT2 inhibition is mediated in part by effects on serum [magnesium] balance remains to be determined.” – by Phil Neuffer

Disclosure: Toto reports he is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Quest Diagnostics, Quintiles, Reata Pharmaceuticals and Relypsa.