Preventing Microalbuminuria in Type 2 Diabetes

Summary

In people with type 2 diabetes, microalbuminuria is a strong, independent risk factor for diabetic nephropathy and cardiovascular morbidity and mortality. ACE inhibitor therapy decreased the risk of microalbuminuria in hypertensive subjects with type 2 diabetes and normoalbuminuria by about 40%. Available data suggest that angiotensin II receptor blockers (ARBs) might have a similar renoprotective effect and that this effect might be increased by combined ACE inhibitor therapy. The study will evaluate the effects, at similar blood pressure control (systolic/diastolic \<130/80 mmHg), for a period of three years, of dual renin-angiotensin-system (RAS) blockade by benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone on microalbuminuria and cardiovascular events in high-risk patients with type 2 diabetes, creatinine \<1.5 mg/dl, no evidence of microalbuminuria but at high risk of renal disease, with hypertension and a urinary albumin excretion between 7 and 19 microgram/min. The relationship between albuminuria and cardiovascular outcomes will also be evaluated. The study is expected to show a more effective prevention of microalbuminuria and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ACE inhibitor, ARB therapy is expected to have a similar effect on microalbuminuria, but an inferior cardioprotective effect. Applied to clinical practice, the findings should help preventing renal and cardiovascular complications, and related treatment costs, of type 2 diabetes.

Timeline

Start

2007-05

Primary completion

2016-07

Completion

2016-09

Publications

• Ruggenenti P, Cortinovis M, Parvanova A, Trillini M, Iliev IP, Bossi AC, Belviso A, Aparicio MC, Trevisan R, Rota S, Perna A, Peracchi T, Rubis N, Martinetti D, Prandini S, Gaspari F, Carrara F, De Cosmo S, Tonolo G, Mangili R, Remuzzi G; VARIETY Study Organization. Preventing microalbuminuria with benazepril, valsartan, and benazepril-valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study. PLoS Med. 2021 Jul 14;18(7):e1003691. doi: 10.1371/journal.pmed.1003691. eCollection 2021 Jul.

Drugs

Indications