Study Shows Impact of Coreg(R) (Carvedilol) on Cardiovascular Risk Factors in Patients With Diabetes and Hypertension

PHILADELPHIA, Nov. 9 /PRNewswire-FirstCall/ — A newer beta-blocker Coreg(R) (carvedilol) may provide advantages in patients with diabetes and hypertension, according to study results released today by GlaxoSmithKline . GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol – Metoprolol Comparison in Hypertensives), a first-of-its-kind trial published in this week’s Journal of the American Medical Association (JAMA) and presented at the 2004 American Heart Association Scientific Sessions, showed a positive impact of Coreg on certain cardiovascular disease risk factors including blood pressure reductions, without negatively affecting HbA1c, a long term measure of blood sugar control, in diabetes patients with hypertension. Aggressive control of cardiovascular risk factors among the approximately 18 million Americans with diabetes is essential because heart disease is the leading cause of death in this population.

“These findings are crucial since very few patients with diabetes have cardiovascular risk factors that are adequately controlled. In fact, it is estimated that only a little over seven percent of people with diabetes achieve treatment goals as recommended by medical experts,” said Dr. George Bakris, Professor in the Departments of Preventive and Internal Medicine, and Director of the Hypertension Research Center at Rush University Medical Center in Chicago. “It is our hope that the GEMINI trial will impact the future of diabetes management because it provides evidence of a positive impact of Coreg on cardiovascular risk factors for this hypertensive patient population without negatively affecting HbA1c.”

GEMINI: Rationale and Background

People with diabetes are at a dramatically increased risk of death from cardiovascular disease. In fact, 80 percent of people with diabetes die of heart disease. Aggressive management of cardiovascular risk factors such as blood pressure, HbA1c, and microalbuminuria are very important since managing these risk factors may reduce the risk of heart attacks, strokes and death. Unfortunately only 25 percent of people with diabetes reach blood pressure goals, about 37 percent reach HbA1c goals and up to 42 percent have microalbuminuria.

Beta-blockers are established and integral medications to successfully manage cardiovascular disease in patients with heart failure, hypertension and those who have had a heart attack. However, despite their life-saving benefits among these patients, the use of beta-blockers is often avoided in patients with diabetes. Traditional beta-blockers have been shown to worsen certain cardiovascular risk factors, such as glycemic control, and have not been shown to improve microalbuminuria levels.

“GEMINI is the first trial to compare the effects of two different beta- blockers on important cardiovascular risk factors,” continued Dr. Bakris. “The results indicate that Coreg may offer positive effects on components of the metabolic syndrome, thus positively impacting patients with diabetes and hypertension.”

Study Design and Results

GEMINI is a six-month, randomized, double-blind active control trial that compared the effects of the newer beta-blocker Coreg to the traditional beta- blocker metoprolol tartrate (marketed by Novartis as Lopressor). The 1,235 patients with type 2 diabetes and hypertension were on standard of care treatment consisting of antidiabetic therapies and ACE inhibitors or angiotensin II receptor blockers. Patients were randomized to receive 6.25 to 25 mg dose of Coreg (n = 498) or 50 to 200 mg dose of metoprolol tartrate (n = 727) each twice daily, and were followed for approximately 6 months.

The primary outcome was the difference in change from baseline HbA1c between groups following 5 months of maintenance therapy. Secondary outcomes that were prespecified included key cardiovascular risk factors such as blood pressure control, glycemic control as measured by HbA1c and insulin resistance, microalbuminuria and weight gain, among others. The effects of the drugs on clinical outcomes have not been compared in long term clinical trials in hypertensive type 2 diabetic patients.

In the GEMINI trial, important results were observed, including:

* Blood Pressure: Patients on Coreg reached protocol specified blood

pressure goals at a mean daily dose that is within the range that is

commonly prescribed (35 mg); patients receiving metoprolol tartrate

required a mean daily dose of 256 mg, a dose not routinely prescribed,

to reach protocol specified blood pressure goals.

* Diabetes control: In patients already receiving antidiabetic therapies,

HbA1c was not negatively affected in patients receiving Coreg while it

worsened in patients receiving metoprolol tartrate. The difference

between Coreg and metoprolol tartrate on HbA1c was 0.13 percent (p =

0.0039) and twice as many patients receiving metoprolol tartrate had

changes of 1.0 percent or greater (p

— In Coreg treated patients, there was a statistically significant

reduction in insulin resistance of 9.1 percent (p = 0.004); the

reduction of insulin resistance of 2.0 percent for metoprolol

tartrate treated patients was not statistically significant.

* Microalbuminuria: The albumin: creatinine ratio (ACR), which is a

measure of microalbuminuria, was measured in all of the patients in the

trial and it was reduced in the patients treated with Coreg by 16

percent (p=0.003) compared to metoprolol tartrate. At the start of the

trial, 80 percent of the patients in GEMINI did not have

microalbuminuria and in that group there was a 47 percent (p=0.03) risk

reduction for the development of microalbuminuria in patients on Coreg

versus those on metoprolol tartrate.

* Weight: Patients taking Coreg did not gain weight. Patients taking

metoprolol tartrate had a weight gain of 2.6 pounds (p

About Coreg

Coreg is marketed by GlaxoSmithKline in the United States and is the only beta-blocking agent FDA approved to improve survival in mild to severe heart failure and is the only beta-blocker approved for reducing cardiovascular mortality in Post MI patients with LV dysfunction. Specific indications include:

* Congestive Heart Failure: Coreg is indicated for the treatment of mild

to severe heart failure of ischemic or cardiomyopathic origin, usually

in addition to diuretics, ACE inhibitor, and digitalis to increase

survival and, also, to reduce the risk of hospitalization.

* Left Ventricular Dysfunction Following Myocardial Infarction: Coreg is

indicated to reduce cardiovascular mortality in clinically stable

patients who have survived the acute phase of a myocardial infarction

and have a left ventricular ejection fraction of

without symptomatic heart failure).

* Hypertension: Coreg is indicated for the management of essential

hypertension.

Important Safety Information

Patients taking Coreg should avoid stopping therapy abruptly. With certain beta-blocking agents, stopping therapy abruptly has led to chest pain, and in some cases, heart attack. The dosage of Coreg should be reduced gradually over a 1- to 2-week period, and the patient should be carefully monitored.

As with any medicine, there are some people who should not take Coreg. The people who should not take Coreg include those with severe heart failure who are hospitalized in the intensive care unit. Also, people who require certain intravenous medications that help support their circulation (inotropic medications) should not receive Coreg. Other people who should not take Coreg are those with asthma or other breathing problems, those with a very slow heartbeat or heart that skips a beat (irregular heartbeat), those with liver disease and those who are allergic to Coreg.

Some common side effects associated with Coreg include shortness of breath, a slow heartbeat, weight gain, fatigue, hypotension, dizziness or faintness. People taking Coreg who have any of these symptoms should call their doctor. Additionally, if patients experience fatigue or dizziness, they should sit or lie down and avoid driving or hazardous tasks. People with diabetes should report any changes in blood sugar levels to their physician. Contact lens wearers may produce fewer tears or have dry eyes. As with any medicine, patients taking Coreg should also first tell their doctor what other medications they are taking.

For full prescribing information on Coreg, call GSK’s U.S. Customer Response Center at 1-888-825-5249 or visit http://www.gsk.com/.

About GlaxoSmithKline

GlaxoSmithKline — one of the world’s leading research-based pharmaceutical and healthcare companies — is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

GlaxoSmithKline

CONTACT: Contact: Nancy Leone GlaxoSmithKline, +1-919-483-2839, orDebbie Kanterman of Cohn & Wolfe, +1-212-798-9739, or C. +1-914-512-0277

Web site: http://www.gsk.com/

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