Clinical proof-of-concept study with MSDC-0160, a prototype mTOT-modulating insulin sensitizer.

ABSTRACT: It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones (mTOT), thereby avoiding peroxisome proliferator-activated receptor-? (PPAR-?)-dependent side effects. In this phase IIb clinical trial, 258 patients with type 2 diabetes completed a 12-week protocol with 50, 100, or 150?mg of MSDC-0160 (an mTOT modulator), 45?mg pioglitazone HCl (a PPAR-? agonist), or a placebo. The two active treatments lowered fasting glucose levels to the same extent. The decreases in glycated hemoglobin (HbA1c) observed with the two higher doses of MSDC-0160 were not different from those associated with pioglitazone. By contrast, fluid retention as evidenced by reduction in hematocrit, red blood cells, and total hemoglobin was 50% less in the MSDC-0160-treated groups. There was also a smaller increase in high-molecular-weight (HMW) adiponectin with MSDC-0160 than with pioglitazone (P < 0.0001), suggesting that MSDC-0160 produces less expansion of white adipose tissue. Thus, mTOT modulators may have glucose-lowering effects similar to those of pioglitazone but without the adverse effects associated with PPAR-? agonists.

SUBMITTER: Colca JR 

PROVIDER: S-EPMC3604641 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature