LISINOPRIL - A REVIEW OF ITS PHARMACOLOGY AND USE IN THE MANAGEMENT OF THE COMPLICATIONS OF DIABETES-MELLITUS

Lisinopril, like other ACE inhibitors, lowers blood pressure and prese rves renal function in hypertensive patients with non-insulin-dependen t or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or li pid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blocke rs, diuretics and beta-blockers, despite similar antihypertensive effi cacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-dependent Diabetes) trial, lisinopril is also renoprotectiv e in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in tho se with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than ne phropathy, lisinopril has shown some benefit. Progression to retinopat hy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convi ncing evidence to date for an effect of an ACE inhibitor in retinopath y. The drug may also improve neurological function, but this finding i s preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicate s that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. Th e tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypogly caemia has occurred at a similar frequency with lisinopril and placebo , as shown in the EUCLID trial. In addition, the GISSI-3 study indicat es that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In sum mary, lisinopril lowers blood pressure and produces a renoprotective e ffect in patients with IDDM and NIDDM without detriment to glycaemic c ontrol or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patient s with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, providers new data supporting an addit ional place in managing normotensive patients with microalbuminuria an d IDDM. These findings, together with some evidence for an effect of l isinopril in delaying progression of retinopathy and in reducing morta lity, suggest broader role for the drug in managing diabetic vascular complications.