National guidelines and a recent clinical trial have supported the use of thiazide diuretics as the preferred initial pharmacological treatment for hypertension. However, evidence from this and other clinical trials have also found an increased incidence of new onset diabetes among those patients receiving thiazide diuretics. The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics have not been fully elucidated. This article provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance. We conducted a literature search from 1966 to June 2004 to identify clinical trials using thiazide diuretics where the metabolic effects on potassium and glucose are reported. A total of 59 clinical trials constituting 83 thiazide diuretic study arms were identified. Trial size, length, type of thiazide diuretic, and dose varied substantially among the studies. The association between average changes in potassium and glucose in the study arms is considered jointly in a weighted statistical model. The Pearson's correlation coefficient, weighted by study sample size, for the relationship between glucose and potassium was -0.54 (95% CI, -0.67 to -0.36; P < 0.01). A sensitivity analysis, which considered subset analyses and effect of covariates, as well as inverse-variance weighting, supported this finding. These data suggest that thiazide-induced hypokalemia is associated with increased blood glucose. Treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent the future development of diabetes.