Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy

TLDR

Diabetic nephropathy is the leading cause of end‑stage renal disease, and while renin‑angiotensin system blockade slows progression in type 1 diabetes, evidence for type 2 diabetes is lacking. The study evaluated losartan’s effect on renal and cardiovascular outcomes in 1,513 patients with type 2 diabetes and nephropathy over a mean 3.4‑year follow‑up. In a randomized, double‑blind trial, patients received losartan (50–100 mg daily) or placebo alongside standard antihypertensives, with the primary endpoint a composite of doubling serum creatinine, end‑stage renal disease, or death, and secondary endpoints including cardiovascular morbidity/mortality, proteinuria, and renal progression. Losartan lowered the risk of doubling creatinine by 25 % and end‑stage renal disease by 28 %, reduced heart‑failure hospitalizations by 32 % and proteinuria by 35 %, had no impact on overall cardiovascular morbidity or mortality, and was well tolerated.

Abstract

Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy.A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease.A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo).Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.