Published Online
on November 14, 2005

A more recent version of this article appeared on December 1, 2005

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Submitted on August 17, 2005
Revised on August 29, 2005

Differential Effects of -Blockers on Albuminuria in Patients With Type 2 Diabetes

George L. Bakris^*; Vivian Fonseca; Richard E. Katholi; Janet B. McGill; Franz Messerli; Robert A. Phillips; Philip Raskin; Jackson T. Wright Jr; Brian Waterhouse; Mary Ann Lukas; Karen M. Anderson; David S.H. Bell; for the GEMINI Investigators

From the Rush University Medical Center (G.L.B.), Chicago, Ill; Tulane University (V.F.), New Orleans, La; St. John’s Hospital (R.E.K.), Springfield, Ill; Washington University School of Medicine (J.B.M.), St. Louis, Mo; St Luke’s Roosevelt Hospital Center (F.M.), New York, NY; Lenox Hill Hospital/New York University (R.A.P.); University of Texas, Dallas (P.R.); Case Western Reserve University (J.T.W.), Cleveland, Ohio; GlaxoSmithKline (B.W., M.A.L., K.M.A.), Philadelphia, Pa; and University of Alabama (D.S.H.B.), Birmingham, Ala.

^* To whom correspondence should be addressed. E-mail: gbakris{at}earthlink.net.

Abstract--Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when -blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different -blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). -Blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or 1-antagonism but may relate to antioxidant properties of carvedilol.

Key words: diabetes mellitus • metoprolol • hypertension, arterial • morbidity

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