Article date: October 2009
By: Patricia N. Sidharta, Klaus Rave, Lutz Heinemann, Eleonora Chiossi, Stephan Krähenbühl, Jasper Dingemanse, in Volume 68, Issue 4, pages 502-510
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIMS
To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin‐II receptor, on insulin and glucose regulation in 20 diet‐treated patients with Type 2 diabetes mellitus in a double‐blind, placebo‐controlled, randomized, crossover, proof‐of‐concept study.
METHODS
After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d., effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment‐insulin resistance score, and daily self‐monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake.
RESULTS
Palosuran did not affect second‐phase insulin response (primary end‐point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of −1.8 µU ml−1, 95% confidence interval (CI) −7.8, 4.2]. Likewise, no effects of palosuran were detected on the first‐phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment‐insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean Cmax and AUCτ (95% CI) and median tmax (range) in this patient population were 180 ng ml−1 (125, 260), 581 ng·h ml−1 (422, 800) and 3.0 h (0.67, 4.3), respectively.
CONCLUSIONS
The results of this study indicate that antagonism of the urotensin‐II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet‐treated patients with Type 2 diabetes.
DOI: 10.1111/j.1365-2125.2009.03480.x
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