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J Diabetes Complications. 2005 Mar-Apr;19(2):74-9.

The rationale and design of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial.

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  • 1Rush Hypertension Center, Rush Medical Center, Suite 470, 1700 W. Van Buren, Chicago, IL 60612, USA.


Beta-blockers utilized in the Type 2 diabetic patient result in an even greater decrease in cardiac events than in the nondiabetic patient. Unfortunately, first-and second-generation beta-blockers are associated with the worsening of insulin resistance, deterioration of glycemic control, peripheral vasoconstriction, potentially worsening peripheral vascular disease, and more frequent and severe hypoglycemia. The third-generation beta-blockers have unique properties, including alpha1-blockade, and have been shown to lower insulin resistance, improve glycemic control, and vasodilate resistance arterioles. The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial has been designed to compare a third-generation (carvedilol) with a second-generation beta-blocker (metoprolol) in a cohort of participants with hypertension and Type 2 diabetes. The primary outcome measure of the study is change in the HbA1c. The study is powered to detect a difference in HbA1c of 0.3 units (%) between the groups. Secondary endpoints include changes in insulin resistance, fasting glucose, and the lipid profile. Differences in the side-effect profile (cold extremities, fatigue, impotence, and hypoglycemia) will also be assessed. The GEMINI trial, therefore, is the first large randomized trial to assess whether utilizing a third-generation beta-blocker yields a favorable metabolic profile in the patient with Type 2 diabetes and hypertension.

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