Effects of rosuvastatin combined with olmesartan, irbesartan, or telmisartan on indices of glucose metabolism in greek adults with impaired fasting glucose, hypertension, and mixed hyperlipidemia: A 24-week, randomized, open-label, prospective study

Abstract

Background: Statin therapy has been reported to be associated with new-onset diabetes. Angiotensin II-receptor blockers (ARBs) are effective antihypertensive drugs that have been reported to activate peroxisome proliferator-activated receptor γ (PPARγ) to differing extents, with favorable effects on glucose metabolism and the incidence of new-onset diabetes. Among the ARBs, telmisartan is a partial activator of PPARγ, irbesartan is a weak partial activator, and olmesartan has no effect on PPARγ activation. Objective: The goal of this study was to evaluate the effects on glucose homeostasis of combining rosuvastatin with ARBs of varying PPARγ-activating potency in Greek adults with impaired fasting glucose, mixed dyslipidemia, and stage 1 hypertension. Methods: This was a 24-week, randomized, open-label study. Inclusion criteria were impaired fasting plasma glucose (FPG) (100–125 mg/dL [5.6–6.9 mmol/L]), mixed dyslipidemia (LDL-C >160 mg/dL [4.14 mmol/L] and triglycerides >150 mg/dL [1.69 mmol/L]), and stage 1 hypertension (systolic blood pressure 140–159 mm Hg and/or diastolic blood pressure 90–99 mm Hg). After 12 weeks of dietary intervention, patients were randomly allocated to receive rosuvastatin 10 mg/d plus telmisartan 80 mg/d (RT group), irbesartan 300 mg/d (RI group), or olmesartan 20 mg/d (RO group) for 24 weeks. The primary end point was change in the following indices of glucose metabolism after 6 months of treatment: FPG, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of β-cell function (HOMA-B), and glycosylated hemoglobin (HbA 1c). Secondary end points included changes in anthropometric variables, blood pressure, serum lipids, and high-sensitivity C-reactive protein (hs-CRP). Tolerability was monitored throughout the study. Results: After the 12-week dietary intervention, 151 white patients (78 female, 73 male) met the inclusion criteria and were randomized to receive RT (n = 52), RI (n = 48), or RO (n = 51). The mean (SD) age of the 3 groups was 60 (10), 60 (10), and 58 (12) years, respectively; their mean weight was 79 (11), 81 (12), and 78 (11) kg. At 6 months, the RT group had a 29% decrease in HOMA-IR (from a median [range] of 2.6 [0.6–6.6] to 1.8 [0.5–5.1]), the RI group had a 16% increase (from 2.5 [0.5–6.2] to 2.9 [0.5–8.1]), and the RO group had a 14% increase (from 2.4 [0.5–7.9] to 2.7 [0.5–5.2]) (all, P < 0.05 vs baseline). The improvement in the RT group was statistically significant compared with the RI group ( P < 0.01) and the RO group ( P < 0.05). The changes from baseline in FPG and HbA 1c were not significant in any group. Fasting serum insulin decreased by 21% in the RT group (from 10.4 [2.4–28.1] to 8.2 [2.4–18.8] μU/mL), whereas it increased by 12% in the RI group (from 9.1 [2.0–26.5] to 10.2 [2.0–25.2] μU/mL) and by 8% in the RO group (from 10.1 [2.0–29.6] to 10.9 [2.0–19.1] μU/mL) (all, P < 0.05 vs baseline). Again, there was a significant difference between the RT group and the RI group ( P < 0.01) and RO group ( P < 0.05). Levels of hs-CRP decreased by 44% in the RT group (from 2.2 [0.3–7.9] to 1.2 [0.4–7.0] mg/L), by 12% in the RI group (from 2.2 [0.3–12.3] to 1.9 [0.2–11.4] mg/L), and by 22% in the RO group (from 2.1 [0.7-4.0] to 1.7 [0.7–6.2] mg/L). The difference was statistically significant for the RT group compared with baseline and with the RI and RO groups (all comparisons, P < 0.05). Blood pressure was significantly reduced from baseline in all 3 groups, with no significant differences between groups. No serious adverse events were reported during the study, nor were there any clinically significant elevations in aminotransferases or creatine kinase. Conclusion: In this small, randomized, open-label study, the RT combination had favorable effects on HOMA-IR, fasting serum insulin, and hs-CRP compared with the RI and RO combinations in Greek adults with impaired fasting glucose, mixed hyperlipidemia, and stage 1 hypertension.