Magnesium Supplementation Could Prevent the Risk of Diabetes from Thiazide Diuretics

By Wanpen Vongpatanasin, M.D.

Professor of Internal Medicine

Thiazide diuretics (TDs) are the first-line treatment of hypertension (HTN) because of a consistent benefit in lowering BP and cardiovascular risk. TDs are also known to cause an excess risk of diabetes mellitus, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TDs also trigger magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TDs has not been investigated – until now. We conducted a double-blinded, randomized clinical trial in 60 nondiabetic hypertensive patients to compare the effects of KCl vs. KMgCitrate during chlorthalidone diuretic treatment, and at #AHA23, I had the privilege of presenting this study.

Each patient received chlorthalidone alone for three weeks before randomization. The primary endpoint was the change in fasting plasma glucose (FPG) after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. We found that chlorthalidone treatment alone for three weeks induced a significant rise in fasting plasma glucose and a significant fall in serum potassium as well as serum magnesium. KMgCit supplementation for 16 weeks attenuated the rise in FPG by 7.9 mg/dL (p < 0.05), a benefit that was not observed with KCl supplementation. KMgCit did not modify the increase in plasma renin or aldosterone levels induced by chlorthalidone, suggesting direct action of magnesium or citrate.

In summary, by preventing both potassium and magnesium depletion, we identified a novel action of potassium magnesium citrate supplementation in preventing a chlorthalidone-induced rise in FPG in hypertensive patients. Future studies are needed to determine the mechanism of KmgCit action and whether its benefit will translate into improved cardiovascular outcomes during TD treatment.

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