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Some Diuretics Can Increase the Risk of Diabetes By 30%

Sep 21, 2015

Despite guideline recommendations to use hydrochlorothiazide early on for blood pressure treatment, current use is limited due to the risk of hyperglycemia and diabetes later on. In fact, concerns about metabolic effects with diuretics are viable considering most studies show an increased risk of diabetes by 25% to 30% when used.

Recent research was presented at the European Society of Cardiology’s annual meeting discussing the use of a combined diuretic, amiloride-HCTZ. Some evidence has suggested the changes in glucose metabolism occurring with diuretics is more related to potassium changes. Thus, the choice to combine amiloride, a potassium-sparing diuretic, with HCTZ.


The study enrolled 440 patients with uncontrolled hypertension (systolic BP >140 mmHg). Patients were given amiloride alone, HCTZ alone or a combination of both medications. Of course, the researchers measured blood pressure, glucose and potassium levels.

The findings were in line with the theory about potassium relating to glucose metabolism. Hydrochlorothiazide alone increased 2-hour OGTT levels when measured at 12 and 24 weeks. On the other hand, amiloride alone decreased 2-hour OGTT levels. Both amiloride and HCTZ alone decreased systolic blood pressure by approximately 14 mmHg.

The combination of both medications together reduced blood pressure by 17.4 mmHg. More importantly, there was a neutral effect on potassium levels, which in turn led to a neutral effect on glucose levels.

Overall, the combination of amiloride-HCTZ may prove useful in treating blood pressure while limiting the risk of developing diabetes due to potassium changes in patients. The research certainly suggests more thought need to be put into guidelines for how to dose and better use diuretics for hypertension patients.

Practice Pearls:

  • Current use of hydrochlorothiazide is limited to low doses due to the known risk of hyperglycemia and diabetes in patients.
  • A recent study combined HCTZ with amiloride to neutralize potassium loss and therefore neutralize glucose changes in patients.
  • The combination of amiloride-HCTZ reduced systolic blood pressure by 17.4 mmHg and had neutral effects on glucose levels.
  • Future guidelines and practitioners may consider how to dose and better use these diuretics in hypertension patients while limiting the risk of diabetes.

European Society of Cardiology. “Comparison of Single and Combination Diuretics in Low-Renin Hypertension (PATHWAY3).” (2015). Web. 4 Sept. 2015. .