RANDOMIZED PLACEBO-CONTROLLED TRIAL OF LISINOPRIL IN NORMOTENSIVE PATIENTS WITH INSULIN-DEPENDENT DIABETES AND NORMOALBUMINURIA OR MICROALBUMINURIA

Background Renal disease in people with insulin-dependent diabetes (ID DM) continues to pose a major health threat. Inhibitors of angiotensin -converting enzyme (ACE) slow the decline of renal function in advance d renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known . Methods We carried out a randomised, double-blind, placebo-controlle d trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20-59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication fo r hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm Hg diastolic, and no more than 155 mm Hg systolic. Ur inary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months. Findings There were no differences in baseline characteristics by tre atment group; mean AER was 8.0 mu g/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril gro ups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 mu g/min lower in the lisinopril than in the placebo group, a perc entage difference of 18.8% (95% CI 2.0-3.27, p=0.03), adjusted for bas eline AER and centre, absolute difference 2 2 mu g/min. In people with normoalbuminuria, the treatment difference was 1.0 mu g/min (12.7% [- 2.9 to 26.0], p=0.1). In those with microalbuminuria, however, the tre atment difference was 34.2 mu g/min (49.7% [-14.5 to 77.9], p=0.1; for interaction, p=0.04). For patients who completed 24 months on the tri al, the final treatment difference in AER was 38.5 mu g/min in those w ith microalbuminuria at baseline (p=0.001), and 0.23 mu g/min in those with narmoalbuminuria at baseline (p=0.6). There was no treatment dif ference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin. Interpretation Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albu minuria, though greatest effect was in those with microalbuminuria (AE R greater than or equal to 20 mu g/min). Our results show that lisinop ril does not increase the risk of hypoglycaemic events in IDDM.