The Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes

TLDR

Microalbuminuria and hypertension are risk factors for diabetic nephropathy, and while renin‑angiotensin system blockade reduces progression in type 1 diabetes, data are lacking for hypertensive type 2 diabetic patients. The study evaluated the renoprotective effect of irbesartan in hypertensive type 2 diabetic patients with microalbuminuria. A multinational, double‑blind, randomized, placebo‑controlled trial with 590 participants compared irbesartan 150 mg, 300 mg, or placebo over two years, with the primary outcome being time to progression to diabetic nephropathy defined by persistent overnight albuminuria >200 µg/min and ≥30 % increase from baseline. Irbesartan 300 mg daily reduced progression to diabetic nephropathy by 70 % (5.2 % vs 14.9 % on placebo, HR 0.30, p < 0.001), while 150 mg showed a non‑significant 35 % reduction; blood pressure was modestly lower and serious adverse events were less frequent, indicating irbesartan is renoprotective, safe, and well tolerated independent of its antihypertensive effect.

Abstract

Microalbuminuria and hypertension are risk factors for the development of diabetic nephropathy. Blockade of the renin-angiotensin system reduces progression to diabetic nephropathy in type 1 diabetic patients, whereas similar data are lacking for hypertensive type 2 diabetic subjects. We evaluated the renoprotective effect of an angiotensin II receptor antagonist, irbesartan, in hypertensive type 2 diabetic patients with microalbuminuria.Five hundred and ninety hypertensive type 2 diabetic patients with microalbuminuria were enrolled in this multinational, randomised, double-blind, placebo-controlled study of irbesartan 150 mg/daily or 300 mg/daily or matching placebo for two years. The primary outcome was time to progression to diabetic nephropathy, defined as a persistent overnight albuminuria > 200 micrograms/min and at least a 30 per cent increase from baseline.Baseline characteristics in the three groups were similar. Ten patients (5.2 per cent) receiving irbesartan 300 mg and 19 patients (9.7 per cent) receiving irbesartan 150 mg daily reached the primary end point, as compared to 30 (14.9 per cent) patients on placebo (hazard ratio 0.30 [95 per cent confidence interval 0.14 to 0.61], p < 0.001 and 0.61 [95 per cent confidence interval 0.34 to 1.08] p = 0.08), respectively). The average blood pressure throughout the study was 144/83, 143/83, and 141/81 mmHg in the placebo, irbesartan 150 mg and 300 mg group, respectively (p = 0.004 for systolic blood pressure). Serious adverse events were less frequent in the patients treated with irbesartan (p = 0.02).Irbesartan is renoprotective independently of its blood pressure lowering effect in type 2 diabetic subjects with microalbuminuria. It is safe and well tolerated.