Elisavet Moutzouri, Anastazia Kei, Evangelos Liberopoulos, Moses Elisaf
Introduction: A potentially diabetogenic role for statins has been suggested. Similarly, first and second generation beta-blockers and hydrochlorothiazide (HCTZ) have negative effects on glucose homeostasis. Nebivolol is a third generation beta-blocker which may beneficially affect carbohydrate metabolism. The effect of combined treatment with nebivolol, HCTZ and atorvastatin is unknown.
Patient and methods: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study. Drug-naive patients with hypertension and dyslipidemia were recruited. All patients received atorvastatin (10 mg). In addition, patients with stage 1 hypertension received nebivolol (5 mg, AN group), while patients with stage 2 hypertension received nebivolol/HCTZ (5/12.5 mg, AN/H-12.5 group or 5/25 mg, AN/H-25 group). The primary efficacy endpoint was the between group mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR) index at 12 weeks.
Results: Seventy-eight patients completed the study. In both AN and AN/H-12.5 group HOMA-IR levels did not significantly change [from 1.6 (1.4-2.1) to 1.5 (1.4-2.0, p=NS) compared with baseline and from 1.6 (1.3-2.2) to 1.7 (1.7-2.4), p=0.07 compared with baseline), respectively]. In contrast, the HOMA-IR significantly increased by 10% in the AN/H-25 group [from 1.7 (1.3-2.3) to 1.9 (1.4-2.4), p=0.02 compared with baseline and p<0.01 for the comparison with the other 2 groups].
Conclusions: Administration of nebivolol may counterbalance the negative effects on HOMA-IR of atorvastatin with or without HCTZ 12.5 mg but not that of atorvastatin plus HCTZ 25 mg.
Keywords: atorvastatin, glucose, HOMA-IR index, hydrochlorothiazide, insulin, nebivolol