Urinary
endothelin (ET)-1 excretion is present in non-
insulin dependent diabetes (
NIDDM) patients with microalbuminuria, and an increase in circulating ET-1 precedes the microalbuminuric phase of renal injury related to diabetes. The aim of the present study was to determine whether various drugs alter urinary ET-1 levels and urinary
albumin excretion (UAE) in
NIDDM patients with microalbuminuria. Forty-five
NIDDM patients with microalbuminuria were randomly assigned to three groups: those treated with
pioglitazone at 30 mg/day (n=15), those treated with
glibenclamide at 5 mg/day (n=15), and those treated with
voglibose at 0.6 mg/day (n=15). Patients received these drugs for 3 months. UAE, urinary ET-1, and plasma ET-1 levels were measured 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 45
NIDDM patients (156.2+/-42.8 microg/min) was greater than that in 30 healthy controls (8.2+/-2.6 microg/min) (P<.001). Urinary ET-1 levels in the
NIDDM patients (8.7+/-1.3 ng/g urinary
creatinine (UC)) were significantly 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).
Pioglitazone but no
glibenclamide or
voglibose reduced UAE from 142.8+/-42.2 to 48. 4+/-18.2 microg/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 reducing UAE and urinary ET-1 concentrations in
NIDDM patients with microalbuminuria.