Effects of Carvedilol and Atenolol in NIDDM and Hypertension
ABSTRACT & COMMENTARY
Synopsis: Although long-term studies are needed to establish both the safety and efficacy of carvedilol in diabetics, the data so far look promising.
Source: Giugliano D, et al. Ann Intern Med 1997;126: 955-959.
Hypertension and cardiovascular disease have high prevalence in diabetics. While many drugs are available to treat hypertension, beta blockers are prescribed with reluctance because of their adverse metabolic effects, including the risk for worsening of glucose tolerance, insulin resistance, and hyperlipidemia. However, the benefit of reduced mortality from cardiovascular causes, in particular myocardial infarction, has been demonstrated in secondary prevention trials. Giugliano and associates conducted a randomized, double-blind, controlled trial to compare the metabolic and cardiovascular effects of carvedilol, a new nonselective beta receptor and selective alpha receptor blocker that prevents lipid peroxidation, and atenolol in 45 non-insulin-dependent diabetic patients with hypertension.
Patients received carvedilol (25 mg once daily) or atenolol (50 mg once daily) for 24 weeks. The drug dose was doubled if diastolic pressure was higher than 90 mmHg or had not dropped by 10 mmHg after four weeks. The baseline characteristics of the patients were similar in both drug groups. The mean age was 58 years, with a 6-7 year duration of diabetes mellitus. Changes in systolic and diastolic blood pressure and left ventricular mass index were similar in both groups. The decrease in heart rate was greater with atenolol (P = 0.005). The differences and superior metabolic profile of carvedilol compared to atenolol are shown in the table.
Table
Metabolic Responses to Carvedilol and Atenolol
Parameter Carvedilol Atenolol P
Total cholesterol ± ¯ ± ¯ NS
Triglyceride ¯ NC < 0.001
HDL ¯ < 0.001
Fasting Glucose ¯ < 0.001
HbA1C ¯ < 0.001
Plasma Insulin pmol/L ¯ < 0.001
Total glucose disposal (20%) ¯ (16%) 0.01
mcmol/kg body wt/min
Insulin sensitivity index ¯ < 0.001
TBARS level mcmol/L NC < 0.001
NC = No change
TBARS = Thiobarbituric acid reactive substances (measure of free radicals)
COMMENT BY KAMALJIT SETHI, MD
The concern about beta blocker use in diabetics is legitimate, given the generally adverse effect on lipids and glycemic control. Carvedilol looks very promising insofar as the metabolic effects are concerned. Compared to atenolol, glucose metabolism and control is improved. Insulin sensitivity is increased because carvedilol increases peripheral blood flow, which may facilitate glucose uptake by muscle cells. The antioxidant activity demonstrated by the reduction in thiobarbituric-acid-reactive substances and the ability to reduce neutrophil-mediated endothelial injury by carvedilol is another beneficial effect.
A recent study demonstrated the usefulness of beta-blocker therapy in NIDDM and coronary artery disease.1 Carvedilol could potentially be the best beta-blocker available, given its metabolic features. Should carvedilol be the beta blocker of choice in diabetics, if one were to use a beta blocker? Long-term studies are needed to establish both safety and efficacy, but the data for carvedilol are quite enticing.
Reference
1. Jones M, et al. Am J Cardiol 1996;77:1273-1277.
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