Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2.
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.
Lerch
M
M
Medizinische Poliklinik, University of Bern, Switzerland.
Weidmann
P
P
Ho
M P
MP
Gerber
P
P
Eckenberger
P
P
Kaemmereit
A
A
Teuscher
A U
AU
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000139:chemically induced; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D050260:Carbohydrate Metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D004311:Double-Blind Method; D004656:Enalapril / Q000493:pharmacokinetics; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D007677:Kidney Function Tests; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D013841:Thiazepines / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D008074:Lipoproteins; D013841:Thiazepines; D004656:Enalapril; C055603:temocapril hydrochloride; D005340:Fibrinogen