BACKGROUND:Abnormal glucose metabolism and insulin resistance have been associated with heart failure incidence, severity, and mortality. Metabolic parameters such as hepatic glucose production may be altered by beta-adrenoceptor antagonists in patients with heart failure. OBJECTIVE: This study evaluated the effects of metoprolol or carvedilol up-titration on fasting glucose, insulin resistance and beta(2)-mediated glucose production in patients with chronic heart failure. METHODS: This was a prospective, randomized, active comparator study in 15 patients with AHA/ACC Stage C systolic dysfunction HF stable on medical therapy. Participants were randomized to metoprolol 25mg daily or carvedilol 3.125mg twice daily. Metoprolol was titrated to a target of 200mg daily, and carvedilol was titrated to 25mg twice daily over 8weeks. Insulin resistance as assessed by the homeostatic model, and terbutaline-induced glucose production (AUC(0-180)), were assessed at baseline and at 4 subsequent beta-blocker titration visits over 8 weeks. RESULTS: In all 15 patients, terbutaline-induced glucose AUC(0-180) decreased (p=0.0006) as beta-blocker doses increased. A significant reduction in glucose AUC(0-180) compared to baseline was only noted in patients taking metoprolol at 100mg daily (-2424.6 [95% CI -372.6 to -4478.4] mg/dL*min) and 200mg daily (-2437.2 [95% CI -15.1 to -4604.4] mg/dL*min), and not observed in those taking carvedilol. After beta-blocker titration, fasting glucose concentrations for the metoprolol and carvedilol groups were 86.9 (95% CI 89.8-101.6) mg/dL and 95.7 (95% CI 89.8-101.6) mg/dL, respectively (p=0.0273), adjusted for baseline values. There was no significant difference between metoprolol and carvedilol on insulin resistance. CONCLUSION: Increasing doses of beta-blockers are associated with decreased in beta2-mediated glucose production in heart failure. Metoprolol, but not carvedilol, decreases hepatic glucose production at commonly used heart failure doses.
RCT Entities:
BACKGROUND:Abnormal glucose metabolism and insulin resistance have been associated with heart failure incidence, severity, and mortality. Metabolic parameters such as hepatic glucose production may be altered by beta-adrenoceptor antagonists in patients with heart failure. OBJECTIVE: This study evaluated the effects of metoprolol or carvedilol up-titration on fasting glucose, insulin resistance and beta(2)-mediated glucose production in patients with chronic heart failure. METHODS: This was a prospective, randomized, active comparator study in 15 patients with AHA/ACC Stage C systolic dysfunction HF stable on medical therapy. Participants were randomized to metoprolol 25mg daily or carvedilol 3.125mg twice daily. Metoprolol was titrated to a target of 200mg daily, and carvedilol was titrated to 25mg twice daily over 8weeks. Insulin resistance as assessed by the homeostatic model, and terbutaline-induced glucose production (AUC(0-180)), were assessed at baseline and at 4 subsequent beta-blocker titration visits over 8 weeks. RESULTS: In all 15 patients, terbutaline-induced glucose AUC(0-180) decreased (p=0.0006) as beta-blocker doses increased. A significant reduction in glucose AUC(0-180) compared to baseline was only noted in patients taking metoprolol at 100mg daily (-2424.6 [95% CI -372.6 to -4478.4] mg/dL*min) and 200mg daily (-2437.2 [95% CI -15.1 to -4604.4] mg/dL*min), and not observed in those taking carvedilol. After beta-blocker titration, fasting glucose concentrations for the metoprolol and carvedilol groups were 86.9 (95% CI 89.8-101.6) mg/dL and 95.7 (95% CI 89.8-101.6) mg/dL, respectively (p=0.0273), adjusted for baseline values. There was no significant difference between metoprolol and carvedilol on insulin resistance. CONCLUSION: Increasing doses of beta-blockers are associated with decreased in beta2-mediated glucose production in heart failure. Metoprolol, but not carvedilol, decreases hepatic glucose production at commonly used heart failure doses.
Authors: J W Swan; S D Anker; C Walton; I F Godsland; A L Clark; F Leyva; J C Stevenson; A J Coats Journal: J Am Coll Cardiol Date: 1997-08 Impact factor: 24.094
Authors: 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 Journal: JAMA Date: 2004-11-10 Impact factor: 56.272
Authors: Christian Torp-Pedersen; Marco Metra; Andrew Charlesworth; Phillip Spark; Mary Ann Lukas; Philip A Poole-Wilson; Karl Swedberg; John G F Cleland; Andrea Di Lenarda; Willem J Remme; Armin Scherhag Journal: Heart Date: 2007-01-19 Impact factor: 5.994