Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes

Abstract

Objective To investigate the metabolic, antihypertensive and albuminuria-modifying effects of a heart rate-modulating calcium antagonist-angiotensin converting enzyme inhibitor combination compared with those of a p-blockerlow-dose diuretic combination in non-insulin-dependent diabetic hypertensives.Design A prospective randomized double-blind study. Subjects and methodsTwenty-four diabetics with diastolic blood pressure 90-115 mm Hg without azotemia (plasma creatinine level < 150jimol/l) were evaluated after 4 weeks receiving placebo and 12 weeks receiving treatment either with combined slow-release verapamil (retard formulation) and trandolapril (mean maintenance doses, 180 and 1.6 mg daily) or with atenolol and chlortalidone (71 and 18mg daily). Insulin sensitivity (by the minimal model method of Bergman), additional metabolic variables, clinic blood pressure, ambulatory blood pressure profile and renal indices were assessed at the end of the placebo and active treatment phases.Results Compared with placebo, the two therapies produced similar decreases in mean supine clinic blood pressure [10±3 versus 11 ±3% (means±SEM)], upright clinic blood pressure (10 ±4 versus 11 ±4%) and ambulatory daytime blood pressure (9±2 versus 12±3%). However, although the verapamil-trandolapril combination was found to be metabolically neutral, the atenolol-chlortalidone combination aggravated insulin resistance [insulin sensitivity index, from (0.8±0.2) to (0.3±0.1)x10~4/min per U per ml], increased the serum triglycerides level and decreased the high-density lipoprotein cholesterol and plasma potassium levels. Although both therapies tended to reduce 24 h albuminuria, this was significant for the verapamil-trandolapril treatment only.Conclusions Because the effect of any antihypertensive drug, including diuretics and p-blockers, on cardiovascular morbidity and on mortality in non-insulin-dependent diabetic patients is not known, rational treatment selection can presently be based only on surrogate end-points. Therefore, the triad of metabolic neutrality with antihypertensive and antiproteinuric efficacy supports combined verapamil-trandolapril as a potentially valuable therapy for hypertension accompanying diabetes mellitus.

Evaluation of the effects of fixed combinations of sustained-release verapamil/trandolapril versus captopril/hydrochlorothiazide on metabolic and electrolyte parameters in patients with essential hypertension

“…The combination verapamil SR and trandolapril has been shown to be metabolically neutral 26 compared to atenolol/chlorthalidone in hypertensive type 2 diabetic patients. The latter combination induced a marked increase in triglycerides.…”

Screening, prevention, counseling, and treatment for the complications of type II diabetes mellitus

“…59 The combination of ␤ -blocker with a thiazide can lead to an increase in plasma glucose levels and should be used with caution. 60,61 Lipids Characteristically, persons with type II diabetes have elevated triglyceride and very-low-density lipoprotein (VLDL) levels, while HDL levels are low. Low-density lipoprotein levels can also be elevated.…”

The Effect of Trandolapril on Insulin Resistance is Determined by the Degree of Baseline Resistance Level

“…Trandolapril was shown to enhance skeletal muscle insulin action and GLUT-4 protein levels in insulin resistant obese rats and it had no effect in insulin sensitive lean rat muscle [19]. In contrast to experimental studies most of the clinical studies conducted indicated that trandolapril has a neutral effect on IR [13][14][15]20]. Only in one clinical study conducted in overweight hypertensive patients with low grade IR trandolapril improved insulin sensitivity moderately compared to nifedipine in the absence of severely obese and diabetic individuals [21].…”

“…Although it was shown to improve IR in insulin resistant obese Zucker or spontaneously hypertensive rat studies [11,12], many clinical studies showed that trandolapril has a neutral effect on IR in hypertensive patients with type 2 DM [13][14][15]. As trandolapril is a lipophylic agent [10], by acting on adipose tissue, it might be more efficient in obese subjects by tissue ACE inhibition.…”