Metabolic Effects of Temocapril in Hypertensive Patients with Diabetes Mellitus Type 2

Abstract

Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.

Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study

“…We confirm previous reports of neutral effects on total cholesterol and triglycerides with both the ACE inhibitor and CCB. [31][32][33] We also corroborate a previous report that indicated small increases in HDL-cholesterol with an ACE inhibitor. 34 More importantly, we noted, that HDLcholesterol also rose with the use of the ACE inhibitor/CCB combination.…”

Therapeutic potential of ACE inhibitors for the treatment of hypertension in Type 2 diabetes

“…In hypertensive Type 2 diabetic patients, captopril increased insulin-mediated glucose uptake by 30% [77]. Although other authors also reported minor beneficial effect on glucose metabolism [78,79], these effects of ACEI have not been confirmed by other groups [80][81][82][83][84]. Some studies have also reported beneficial effects of ACEI on plasma lipid levels [78,82,[84][85][86].…”

“…On the other hand, significantly more patients in the enalapril group were treated with the combination of antihypertensive agents including the β-blocker and diuretic. The analysis included both patients assigned for intensive blood pressure treatment aiming at target diastolic pressure 75 mmHg and patients assigned to moderate pressure control (80)(81)(82)(83)(84)(85)(86)(87)(88)(89). Importantly, the difference in incidence of MI lead investigators to a decision to terminate the nisoldipine treatment in hypertensive NIDDM patients and the follow-up continues only in normotensive patients.…”

Defects in insulin action in chronic heart failure

“…There is some evidence that ACE inhibitors have a modest beneficial effect on insulin sensitivity and this could be an added bonus of ACE inhibitor treatment[112–114]. However, in several placebo controlled trials no beneficial effect of ACE inhibitors on insulin sensitivity has been found[115–117] and the controversy is still ongoing. In this context also the mechanism whereby ACE inhibitors may modulate insulin effectiveness on glucose disposal remain unclear.…”