Carvedilol vs. metoprolol: A comparison of effects on endothelial function and oxidative stress in response to acute hyperglycemia in patients with type 2 diabetes and hypertension

Introduction: The GEMINI trial compared the effects of treatment with metoprolol versus carvedilol in patients with type 2 diabetes. Carvedilol demonstrated a more favorable effect on factors associated with the metabolic syndrome than metoprolol. We hypothesize that carvedilol will have additional beneficial effects on markers of inflammation, oxidative stress, and endothelial function than metoprolol. Methods: Twenty subjects were randomized to either carvedilol or metoprolol. Study procedures including assessment of metabolic parameters and endothelial function, while fasting and after a 75 g oral glucose tolerance were conducted at baseline and following 5 months of treatment. Results: Following 5 months of treatment, PAI-1 increased significantly from baseline in the metoprolol group. There were no changes in PAI-1 in the carvedilol group. While not reaching statistical significance, there was a trend toward worsening insulin resistance with metoprolol treatment compared to carvedilol treatment. Flow mediated vasodilation increased in both groups following the 2-hr OGGT during the baseline study. After five months of treatment, there was a non-significant increase in flow-mediated vasodilation under both fasting and post OGTT conditions in the carvedilol group compared to baseline. Conversely, there was no change in fasting flow mediated vasodilation in the metoprolol group. Additionally, metoprolol treatment blunted the increase in flow mediated vasodilation following OGGT compared to baseline (p < 0.05). Conclusion: Treatment with metoprolol was associated with adverse metabolic effects including increases in PAI-1 and trends toward worsening insulin resistance and endothelial function compared to treatment with carvedilol.