The safety, tolerability and efficacy of BRL 49653C in patients with NIDDM has been examined in a phase II, double-blind, placebo controlled dose response study. A total of 380 patients received either placebo, 005mg bid, 0.25mg bid, 1mg bid or 2mg bid for 12 weeks. Analysis of variance showed highly significant (p<0.001) treatment effects on fasting blood glucose from week 2 onwards, although it was clear that a plateau in response had not been achieved at the highest dose tested. At the higher dose of 2mg bid, there were statistically significant differences compared to placebo, at week 12 for fasting plasma glucose (-40.1 mg/dL), fructosamine (-27.1 mmol/L) and insulin (-16%), and a significant reduction in hemoglobin Alc (0.4%). The lowering of fasting glucose in the 2mg bid group with a concomitant 16% decrease in insulin levels supports the hypothesis of insulin sensitization as a mechanism of action for BRL 49653.