Effects of β-blocker titration on glucose homeostasis in heart failure

Orly Vardeny, James Zebrack, Edward M. Gilbert, Kai I. Cheang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Abnormal glucose metabolism and insulin resistance have been associated with heart failure (HF) incidence, severity, and mortality. Metabolic parameters such as hepatic glucose production may be altered by β-adrenoceptor antagonists in patients with HF. Objective: To evaluate the effects of metoprolol succinate or carvedilol uβtitration on fasting glucose, insulin resistance, and β2-mediated glucose production in patients with chronic HF. Methods: This was a prospective, randomized, active comparator study in 15 patients with American Heart Association/American College of Cardiology Stage C systolic dysfunction HF that was stabilized with medical therapy. Participants were randomized to receive metoprolol succinate 25 mg daily or carvedilol 3.125 mg twice daily. Metoprolol was titrated to a target of 200 mg daily, and carvedilol was titrated to 25 mg twice daily over 8 weeks. Insulin resistance as assessed by the homeostatic model and terbutaline-induced glucose production (area under the curve from 0 to 180 ⋯ [AUC0-180]) were assessed at baseline and at 4 subsequent β-blocker titration visits over 8 weeks. Results: In all 15 patients, terbutaline-induced glucose AUC0-180 decreased (p = 0.001) as β-blocker doses increased. A significant reduction in glucose AUC 0-180 compared with baseline was noted only in patients taking metoprolol 100 mg daily (-2424.6 mg/dL·min; 95% CI 372.6 to -4478.4) and 200 mg daily (-2437.2 mg/dL·min; 95% CI -15.1 to -4604.4) and was not observed in those taking carvedilol. After βblocker titration, fasting glucose concentrations for the metoprolol and carvedilol groups were 86.9 mg/dL (95% CI 89.8 to 101.6) and 95.7 mg/dL (95% CI 89.8 to 101.6), respectively (p = 0.027), adjusted for baseline values. There was no significant difference between the effect of metoprolol and carvedilol on insulin resistance. Conclusions: Increasing doses of βblockers are associated with decreased βz mediated glucose production in HF. Metoprolol succinate, but not carvedilol, decreases hepatic glucose production at doses commonly used in HF.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalJournal of Pharmacy Technology
Issue number2
StatePublished - 2009


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