Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND)

Aims: Intervention studies have shown that angiotensin receptor blockers (ARB) may reduce the incidence of type 2 diabetes mellitus. It is currently unclear whether short-term therapy with ARBs affects metabolic parameters. Methods: i-RESPOND, a randomised, controlled, multicentre, double-blind study evaluated the effect of 16 weeks of irbesartan vs. hydrochlorothiazide (HCTZ) on insulin resistance as well as on lipid and inflammatory parameters in hypertensive subjects with metabolic syndrome. Patients received irbesartan (150 mg/d; n = 211) or HCTZ (12.5 mg/d; n = 215), titrated to 300 mg/day and 25 mg/day respectively. In a second part of the study (weeks 16-28), patients initially randomised to irbesartan received additional HCTZ and vice versa. Results: At week 16 both irbesartan and HCTZ had no effect on insulin resistance measured by the Matzuda index and beta-cell function. Similarly, in the second part of the study (week 16-28) no differences between irbesartan and HCTZ with respect to glucose metabolism were observed. However, irbesartan induced beneficial changes in high-sensitivity-C-reactive protein (hs-CRP) (irbesartan: -5.5 ± 5.2%; HCTZ + 19.9 ± 6.5%, p = 0.0024) and in urinary albumin/creatinine ratio (ACR) (irbesartan: -13%; HCTZ + 9%; p = 0.0041) compared with HCTZ despite a similar decrease in blood pressure in both treatment groups. Irbesartan and HCTZ were well tolerated and adverse events were comparable. Conclusion: Irbesartan did not show significant favourable effects on insulin resistance compared with HCTZ in this study; however, may have beneficial effects on inflammation and microalbuminuria in hypertensive patients with metabolic syndrome.