Efficacy and Reduced Metabolic Side Effects of a 15-mg Chlorthalidone Formulation in the Treatment of Mild Hypertension

Abstract

We compared a new low-dose chlorthalidone formulation consisting of 15 mg of this compound and a biocompatible polymer in a double-blind placebo-controlled trial with the standard 25-mg dose of chlorthalidone in the management of mild essential hypertension. Two hundred twenty-two patients, ranging in age from 21 to 69 years, with an average standing diastolic blood pressure between 91 and 104 mm Hg participated in this trial. At the end of 12 weeks, the percentage of patients who had a decrease in their standing diastolic blood pressure of 5 mm Hg or more was statistically similar in both of the active-treatment groups and significantly different from the placebo group. With the lower-dose compound, the metabolic side effect of hypokalemia was less of a problem and there was no evidence of glucose intolerance. Thus, this new 15-mg formulation of chlorthalidone appears to be an effective antihypertensive agent with fewer metabolic side effects compared with the standard 25-mg dose in the management of mild essential hypertension.

Thiazide-Induced Dysglycemia

“…Diuretic-related reductions in serum K ϩ are typically dose related and usually range from 0.2 to 0.6 mmol/L. [11][12][13][14][37][38][39][40][41] This well-described relationship is depicted by arrow "A" in Figure 1. A recent meta-analysis of 59 studies involving 83 thiazide diuretic treatment arms found a significant correlation between the degree of diuretic-induced hypokalemia and the increase in plasma glucose, and there was evidence that prevention of hypokalemia with K ϩ supplementation or potassium-sparing agents lessened the degree to which plasma glucose increased consequent to diuretic therapy.…”

Diuretics in the therapy of hypertension

“…[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][36][37][38][39][40][41][42] The only biochemical variable that is affected by most antihypertensive diuretics irrespective of the dose is serum uric acid concentration, which undergoes a small increase, on average, even when low doses are used. 13,21,43 Cicletanine 50 mg does not modify the renal handling of urate, 44 and it does not elevate serum uric acid concentration.…”

Drug Treatment of Hypertension in Patients With Diabetes Mellitus

“…However, it is still not certain whether low doses of these drugs will be as effective in reducing BP as high doses have been. In a large multicenter trial of patients with essential hypertension, Vardan et al (169) noted that 15 and 25 mg of chlorthalidone had equivalent antihypertensive efficacy, but the lower dose caused minimal metabolic changes, specifically, not raising plasma glucose or significantly altering lipid levels. Similarly, Berglund etal.…”