Hyperglycemia and hypokalemia are well-recognized consequences of thiazide diuretic (TZD) therapy. Both adversities appear to be dose-related, and since we currently generally use low-dose TZD for treatment of hypertension (the most common indication for TZD therapy), it is useful to identify its impact on metabolic parameters.

Mukete and Rosendorff performed a meta-analysis on clinical trial data of 17,947 subjects in whom potassium (K+) and glucose measurements were taken. Overall, the mean changes in both parameters compared to other treatments were modest: an increase of glucose of only 1.4 mg/dL and a decrease in K+ of 0.27 mEq/L.

The largest hypertension trial ever performed was the ALLHAT trial, which found that compared to the calcium channel blocker amlodipine or the ACE inhibitor lisinopril, diuretic therapy was associated with a small but statistically significant increased risk for new onset diabetes (8.1% vs 9.8% vs 11.6%, respectively). Although looking at mean changes of metabolic parameters, especially restricting the view to only low-dose thiazides, looks relatively reassuring, the fact that some outliers will still experience clinically relevant hypokalemia or hyperglycemia mandates our continued vigilance for both consequences during the course of long-term treatment.