TY  - JOUR
T1  - Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: A randomized controlled trial
AU  - Bakris GL, Fonseca V, Katholi RE, et al
Y1  - 2004/11/10
N1  - 10.1001/jama.292.18.2227
JO  - JAMA
SP  - 2227
EP  - 2236
VL  - 292
IS  - 18
N2  - Context 
                  β-Blockers have been shown to decrease cardiovascular risk in patients
with hypertension and type 2 diabetes mellitus (DM); however, some components
of the metabolic syndrome are worsened by some β-blockers.Objective 
                  To compare the effects of β-blockers with different pharmacological
profiles on glycemic and metabolic control in participants with DM and hypertension
receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular
risk factors.Design, Setting, and Participants 
                  A randomized, double-blind, parallel-group trial (The Glycemic Effects
in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI])
conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared
the effects of carvedilol and metoprolol tartrate on glycemic control. The
1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg)
and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and
were receiving RAS blockers. Participants were followed up for 35 weeks.Interventions 
                  Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol
(n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737),
each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium
antagonist were added, if needed, to achieve blood pressure target.Main Outcome Measures 
                  Difference between groups in mean change from baseline HbA1c following
5 months of maintenance therapy. Additional prespecified comparisons included
change from baseline HbA1c in individual treatment groups, treatment
effect on insulin sensitivity, and microalbuminuria.Results 
                  The 2 groups differed in mean change in HbA1c from baseline
(0.13%; 95% confidence interval [CI], –0.22% to –0.04%; P = .004; modified intention-to-treat analysis).
The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol
(–9.1%; P = .004) but not metoprolol
(–2.0%; P = .48); the between-group
difference was –7.2% (95% CI, –13.8% to –0.2%; P = .004). Blood pressure was similar between groups. Progression
to microalbuminuria was less frequent with carvedilol than with metoprolol
(6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04).Conclusions 
                  Both β-blockers were well tolerated; use of carvedilol in the presence
of RAS blockade did not affect glycemic control and improved some components
of the metabolic syndrome relative to metoprolol in participants with DM and
hypertension. The effects of the 2 β-blockers on clinical outcomes need
to be compared in long-term clinical trials.
SN  - 0098-7484
M3  - doi: 10.1001/jama.292.18.2227
UR  - http://dx.doi.org/10.1001/jama.292.18.2227
ER  -