Selective modulation of PPARγ activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes

Abstract Objective INT131 besylate is a potent non-thiazolidinedione selective peroxisome proliferator-activated receptor γ (PPARγ)  modulator (SPPARM) designed to improve insulin sensitivity and glucose metabolism while minimizing the side effects of full agonist thiazolidinediones. This study was conducted to determine short-term efficacy and safety of INT131 besylate in patients with Type 2 diabetes mellitus (T2DM). Research Design and Methods This was a 4-week randomized, double-blind, placebo-controlled multi-center study with 1 or 10mg INT131 besylate or placebo daily in subjects with T2DM not receiving pharmacotherapy for their hyperglycemia. The primary efficacy analysis was the comparison of treatment groups with respect to least square mean change from baseline to Week 4 of fasting plasma glucose (FPG). Results Baseline mean (±S.D.) FPG for the study population was 171±42 mg/dl. Change in FPG (±S.E., mg/dl) from baseline after 4 weeks was 8±8 ( P =NS) with placebo, -22±8 with 1mg INT131 besylate ( P =.0056) and −46±7 with 10mg INT131 besylate ( P Conclusions INT131 besylate demonstrated a dose dependent reduction in FPG. The FPG reduction with 1mg INT131 besylate was comparable to the modeled 8 mg dose of rosiglitazone, and did not cause fluid retention or weight gain. These results are consistent with the INT131 SPPARM design.