In the Zucker rat model of diabetes, an initial evaluation of in vivo activity reveals significant reductions in glucose, HbA1C, triglycerides, and total cholesterol following intravenous administration of 10 mg/kg Indeglitazar once daily for 3 weeks. Notably, adiponectin levels remain essentially unchanged between treated and untreated animals (4.8 mcg/mL vs. 4.9 mcg/mL) on day 21, suggesting that the observed improvements in glucose and HbA1C are independent of adiponectin. These differences in Indeglitazar's in vivo effects may stem from synergies among its three PPAR activities or its selective PPAR modulation (SPPARM) profile, or a combination thereof. Additionally, the oral activity of Indeglitazar is assessed in the ob/ob model of diabetes and insulin resistance, where it significantly reduces levels of glucose, insulin, triglycerides, and free fatty acids ^[1].

In a preadipocyte differentiation assay assessing the functional insulin sensitization capability, Indeglitazar exhibits an EC50 of 0.32 μM, whereas Rosiglitazone demonstrates an EC50 of 13 nM. However, the maximal response from both compounds is comparable ^[1].