?2-mediated glucose production during carvedilol and metoprolol titration in heart failure

Background Metoprolol and carvedilol are commonly used in heart failure (HF). Previous studies in hypertension indicate worsening of insulin sensitivity with metoprolol but not with carvedilol. However in HF, their relative effects on glucose production have not been directly compared. This study compares fasting glucose and β2-mediated glucose production during metoprolol and carvedilol titration in HF patients. Methods From a previous cohort of HF subjects whose metoprolol or carvedilol were titrated to maximally tolerated doses (up to metoprolol 200mg/d or carvedilol 25mg twice daily) over 5 visits, we analyzed (1) fasting glucose and (2) glucose AUC0–180min upon a β2-agonist (terbutaline) infusion in nondiabetic individuals. Results Fasting glucose (mg/dL) in the metoprolol group (n=9) decreased from 91.1±2.6 (baseline) to 86.9±2.0 (end of titration) while it increased from 91.8±3.1 to 95.7±2.6 with carvedilol (n=6) (p=0.0273, ANCOVA for the comparison between groups). AUC0–180 (mmol/L× 180 min) upon terbutaline infusion decreased from 5.6±0.3 to 4.8±0.1 with metoprolol versus from 5.8±0.3 to 5.0±0.1 with carvedilol (p=NS). AUC0–180 for both metoprolol and carvedilol decreases as drug dosages increase (p=0.0006, repeated measures ANOVA), with a trend toward bigger reduction with metoprolol. Conclusions Metoprolol and carvedilol at clinically relevant doses do not impair fasting glucose in HF. As beta blockade increases, β2-mediated glucose production is reduced. Clinical Pharmacology & Therapeutics (2005) 77, P54–P54; doi: 10.1016/j.clpt.2004.12.096