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Enhances insulin sensitivity: carvedilol praised for its antidiabetic effects.

SNOWMASS, COLO. -- Carvedilol possesses unique insulin-sensitizing properties that make it the [beta]-blocker of choice, not only in treating congestive heart failure but also for the treatment of hypertension and in the post-MI setting, Dr. John S. Schroeder said at a conference sponsored by the American College of Cardiology.

Other [beta]-blockers increase insulin resistance; carvedilol (Coreg), a nonselective [beta]-blocker, reduces it. That carvedilol's antidiabetic effect hasn't received much mention is surprising, given that continuing medical education programs have lately exhorted physicians to reduce both the risk of cardiovascular disease in diabetic patients and the risk of diabetes in patients with heart disease, said Dr. Schroeder, professor of medicine at Stanford (Calif.) University.

The most recent illustration of carvedilol's antidiabetic effect comes from the landmark randomized Carvedilol or Metoprolol European Trial (COMET) involving more than 3,000 patients with congestive heart failure, presented last fall in Vienna at the annual congress of the European Society of Cardiology.

COMET patients treated with carvedilol showed a highly significant 17% reduction in relative risk of mortality--the primary study end point--compared with those receiving metoprolol. That was the finding that grabbed headlines in the summer of 2003. But carvedilol-treated patients also had a 23% relative risk reduction in new-onset diabetes, a prespecified secondary end point, Dr. Schroeder noted.

An analysis of all-cause mortality by diabetic status in nearly 1,100 patients with congestive heart failure in earlier U.S. placebo-controlled carvedilol trials showed mortality reductions that were equally significant in diabetic and nondiabetic carvedilol-treated patients. By contrast, in the Metoprolol CR/XL Randomized Interventional Trial in Congestive Heart Failure (MERIT-HF) only the nondiabetic patients had a statistically significant reduction in mortality.

Carvedilol's insulin-sensitizing effect has been known since the mid-1990s. In one study involving multiple [beta]-blockers in hypertensive patients, carvedilol was associated with an improvement from a baseline of about 15% in insulin sensitivity, compared with decreases exceeding 20% with atenolol and metoprolol, which are [[beta].sub.2]-selective agents. This adverse metabolic effect was even more pronounced in patients who received propranolol, another [[beta].sub.2]-selective agent (Am. J. Hypertens, 11[10]:1258-65, 1998).

The difference between metoprolol and the other [beta]-blockers amounted to a 25%-40% change in insulin sensitivity. That's similar to the metabolic effect of taking an insulin-sensitizing agent such as a glitazone or metformin, Dr. Schroeder said.

In another study, this time in diabetic hypertensive patients, 6 months of carvedilol at 25 mg/day resulted in a mean 5.4% reduction in fasting plasma glucose level, compared with baseline, while 50 mg/day of atenolol led to a 3.6% increase. The glycosylated hemoglobin level fell by 0.1% in the carvedilol group, compared with a 0.3% rise in atenolol-treated patients. Glucose disposal, triglyceride levels, HDL levels, and glucose oxidation were other metabolic parameters that benefited from carvedilol and worsened with atenolol, the cardiologist said.

"I know atenolol is everybody's favorite [beta]-blocker, but there's evidence it has adverse effects not only on glucose but on lipids. As cardiologists, you all serve as the fund of knowledge for cardiovascular recommendations in your community. And even though you don't treat a lot of hypertension directly, if your referring physicians are still using atenolol, you're causing diabetes over the next 5-10 years in those patients," Dr. Schroeder said.

BY BRUCE JANCIN

Denver Bureau
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Title Annotation:Cardiovascular Medicine
Author:Jancin, Bruce
Publication:Internal Medicine News
Date:Mar 1, 2004
Words:557
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