Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients

Urinary endothelin (ET)-1 excretion is present in non-insulin dependent dia betes (NIDDM) patients with microalbuminuria, and an increase in circulatin g ET-1 precedes the microalbuminuric phase of renal injury related to diabe tes. The aim of the present study was to determine whether various drugs al ter urinary ET-1 levels and urinary albumin excretion (UAE) in NIDDM patien ts with microalbuminuria. Forty-five NIDDM patients with microalbuminuria m ere randomly assigned to three groups: those treated with pioglitazone at 3 0 mg/day (n = 15), those treated with glibenclamide at 5 mg/day (n = 15), a nd those treated with voglibose at 0.6 mg/day (n = 15). Patients received t hese drugs for 3 months. UAE, urinary ET-1, and plasma ET-1 levels were mea sured in these patients before and after treatment. Before treatment, UAE, urinary ET-1, and plasma ET-1 levels differed little among the three groups . UAE in the 15 NIDDM patients (156.2+/-42.8 mug/min) was seater than that in 30 healthy controls (8.2+/-26 mug/min) (P<.001). Urinary ET-1 levels in the NIDDM patients (8.7+/-1.3 ng/g urinary creatinine (UC)) were significan tly higher than that in the controls (2.4+/-0.2 ng/g UC) (P<.01). Plasma ET -1 levels, however, in the NIDDM patients (1.3+/-0.4 pg/ml) did not differ significantly from the levels in healthy controls (1.0+/-0.6 pg/ml). Piogli tazone but no glibenclamide or voglibose reduced UAE from 142.8+/-42.2 to 4 8.4+/-18.2 mug/min (P<.01) and urinary ET-1 levels from 8.6+/-1.3 to 3.4+/- 0.5 ng/g UC (P<.01). These data suggest pioglitazone to be effective in red ucing UAE and urinary ET-1 concentrations in NIDDM patients with microalbum inuria. (C) 2000 Elsevier Science Inc. All rights reserved.