Double-Blind Randomized Cross-Over Trial Comparing Metabolic Effects of Candesartan, Hydrochlorothiazide and Placebo

To investigate the mechanisms underlaying the diabetes-preventing effect of candesartan with respect to possible impact on insulin sensitivity, beta cell function and adipose tissue function and distribution. For this purpose comparisons will be performed with hydrochlorothiazide and placebo treatment. It is hypothesized that candesartan will improve insulin sensitivity as compared to hydrochlorothiazide and possibly also in comparison with placebo and that this could be explained by altered fat tissue function or distribution or by an altered sympathetic to parasympathetic balance in the autonomic nervous system. Hydrochlorthiazide is chosen as comparator because thiazides are a recommended firs-line therapy in hypertension. This drug class has some detrimental effects on glucose tolerance and in insulin sensitivity.

Inclusion criteria

• Male and female 18-70 years old
• Diagnosed hypertension and abdominal obesity (waist circumference greater than or equal to 102 cm (M) or 88 cm (F)

Exclusion criteria

• Uncontrolled hypertension
• Treatment with more than two concomitant antihypertensive medications
• Diabetes Mellitus
• Other endocrine disorder
• Severe liver disease
• Severely reduced renal function
• Malignant disease
• Alcohol or drug abuse
• Severe psychiatric illness
• History of stroke, myocardial infarction, unstable angina pectoris, participation in another clinical trial less than two months prior to screening visit
• treatment with anti-obesity drugs
• anti-inflammatory drugs or immunosuppressive drugs