Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: A randomized controlled trial

George L. Bakris, Vivian Fonseca, Richard E. Katholi, Janet B. McGill, Franz H. Messerli, Robert A. Phillips, Philip Raskin, Jackson T. Wright, Rosemary Oakes, Mary Ann Lukas, Karen M. Anderson, David S H Bell

Research output: Contribution to journalArticle

578 Citations (Scopus)

Abstract

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 HbA 1c 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.

Original languageEnglish (US)
Pages (from-to)2227-2236
Number of pages10
JournalJournal of the American Medical Association
Volume292
Issue number18
DOIs
StatePublished - Nov 10 2004

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Metoprolol
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Hypertension
Renin-Angiotensin System
Diabetes Mellitus
Confidence Intervals
Insulin Resistance
Blood Pressure
Intention to Treat Analysis
Hydrochlorothiazide
Glycosylated Hemoglobin A
carvedilol
Therapeutics
Odds Ratio
Outcome Assessment (Health Care)
Clinical Trials
Pharmacology
Calcium

ASJC Scopus subject areas

  • Medicine(all)

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Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension : A randomized controlled trial. / Bakris, George L.; Fonseca, Vivian; Katholi, Richard E.; McGill, Janet B.; Messerli, Franz H.; Phillips, Robert A.; Raskin, Philip; Wright, Jackson T.; Oakes, Rosemary; Lukas, Mary Ann; Anderson, Karen M.; Bell, David S H.

In: Journal of the American Medical Association, Vol. 292, No. 18, 10.11.2004, p. 2227-2236.

Research output: Contribution to journalArticle

Bakris, GL, Fonseca, V, Katholi, RE, McGill, JB, Messerli, FH, Phillips, RA, Raskin, P, Wright, JT, Oakes, R, Lukas, MA, Anderson, KM & Bell, DSH 2004, 'Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: A randomized controlled trial', Journal of the American Medical Association, vol. 292, no. 18, pp. 2227-2236. https://doi.org/10.1001/jama.292.18.2227
Bakris, George L. ; Fonseca, Vivian ; Katholi, Richard E. ; McGill, Janet B. ; Messerli, Franz H. ; Phillips, Robert A. ; Raskin, Philip ; Wright, Jackson T. ; Oakes, Rosemary ; Lukas, Mary Ann ; Anderson, Karen M. ; Bell, David S H. / Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension : A randomized controlled trial. In: Journal of the American Medical Association. 2004 ; Vol. 292, No. 18. pp. 2227-2236.
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abstract = "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 HbA 1c 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.",
author = "Bakris, {George L.} and Vivian Fonseca and Katholi, {Richard E.} and McGill, {Janet B.} and Messerli, {Franz H.} and Phillips, {Robert A.} and Philip Raskin and Wright, {Jackson T.} and Rosemary Oakes and Lukas, {Mary Ann} and Anderson, {Karen M.} and Bell, {David S H}",
year = "2004",
month = "11",
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doi = "10.1001/jama.292.18.2227",
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volume = "292",
pages = "2227--2236",
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TY - JOUR

T1 - Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension

T2 - A randomized controlled trial

AU - Bakris, George L.

AU - Fonseca, Vivian

AU - Katholi, Richard E.

AU - McGill, Janet B.

AU - Messerli, Franz H.

AU - Phillips, Robert A.

AU - Raskin, Philip

AU - Wright, Jackson T.

AU - Oakes, Rosemary

AU - Lukas, Mary Ann

AU - Anderson, Karen M.

AU - Bell, David S H

PY - 2004/11/10

Y1 - 2004/11/10

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 HbA 1c 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.

AB - 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 HbA 1c 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.

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