EFFECT OF NEW ORAL ANTIDIABETIC AGENT CS-045 ON GLUCOSE-TOLERANCE AND INSULIN-SECRETION IN PATIENTS WITH NIDDM

Objective: To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods: Nineteen NIDDM patients (mean t SD age 48.9 t 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (> 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. Results: The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA(1c) decreased (n = 19, FPG, 11 +/- 2.4 vs. 8.4 +/- 2.7 mM [before vs. after], P < 0.001; HbA(1c), 8.0 +/- 1.1 vs. 7.4 +/- 1.3%, P < 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 +/- 49.8 vs. 56.5 +/- 24.6 pM [before vs. after], P < 0.05; area under the curve of IRI, 540.3 +/- 350.5 vs. 426.4 +/- 216.3 pM . h, P < 0.05). Conclusions: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.