Recently, the ARBs losartan potassium and irbesartan have been shown in patients with type 2 diabetes mellitus to decrease the progression from microalbuminuria to albuminuria and to slow the progression of diabetic nephropathy.2- 4 In the IRMA (Irbesartan for Microalbuminuria in Type 2 Diabetes) study,2 590 patients with type 2 diabetes mellitus with microalbuminuria, normal renal function, and BP greater than 135/85 mm Hg were randomized to treatment with either placebo or irbesartan (150 mg/d or 300 mg/d). At the end of 2 years, progression to macroalbuminuria occurred in 14.9% of patients receiving placebo and in 9.7% and 5.2% in the groups given irbesartan, 150 mg/d and 300 mg/d, respectively. Blood pressures in the 3 groups were 144/83 mm Hg (placebo), 143/83 mm Hg (irbesartan, 150 mg/d) and 141/83 mm Hg (irbesartan, 300 mg/d). This study demonstrates a dose-dependent reduction in the incidence of progression from microalbuminuria to macroalbuminuria. The IDNT (Irbesartan Diabetic Nephropathy Trial) enrolled 1715 patients with type 2 diabetes mellitus, proteinuria (>900 mg/d), and creatinine levels between 1.0 and 3.0 mg/dL (88-265 µmol/L).3 Patients were randomized to receive either irbesartan (300 mg/d), amlodipine besylate (10 mg/d), or placebo. Placebo treatment consisted of placebo medication plus conventional antihypertensive medications. The trial lasted 2.6 years and had as its primary composite end point the doubling of serum creatinine levels, reaching ESRD, or death. The BP goal was 135/85 mm Hg in all groups; however, actual attained levels were 140/77 mm Hg in both the irbesartan and amlodipine groups and 144/82 mm Hg in the placebo group. In the irbesartan group, patients had a 20% lower unadjusted relative risk of reaching the primary end point than the placebo group (P = .02) and 23% lower than in the amlodipine group (P = .006). The unadjusted relative risk of doubling of serum creatinine levels in the irbesartan group was 33% lower than the placebo group (P = .003) and 37% lower than the amlodipine group (P<.001). Last, in the RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) trial,4 1513 patients with type 2 diabetes mellitus, urine albumin excretion greater than 300-mg/g creatinine (mean, 4 g/d), and serum creatinine levels between 1.3 and 3.0 mg/dL (115-265 µmol/L) were randomized to receive either placebo or losartan (beginning at 50 mg/d and increasing to 100 mg/d at 4 weeks if BP was not controlled). The study was terminated at 3.4 years of follow-up because of evidence from the HOPE trial11 that the ACE inhibitor ramipril led to cardiovascular protection in patients with type 2 diabetes mellitus at high risk for future CVD. Proteinuria decreased by 35% with losartan and did not change with placebo, while at study end point, BP measurements were nearly identical for both groups. In the losartan group, patients had a 16% reduction in the primary composite end point (time to doubling of serum creatinine levels, ESRD, or death) (P = .02). In addition, losartan led to a risk reduction of 25% for time to doubling of serum creatinine levels (P = .006) and of 28% for ESRD (P = .002). In summary, 3 recent trials have provided convincing evidence that in patients with type 2 diabetes mellitus with either microalbuminuria or overt diabetic nephropathy, ARBs reduce the progression of renal disease.