Science / Insulin Sensitizers

Insulin sensitizers were discovered more than 25 years ago. They have been shown through more than 13 years of clinical use to have positive, durable effects in the treatment of diabetes. More than a decade after the first insulin sensitizers were discovered, the activation of the nuclear receptor PPARγ was hypothesized to be the mechanism of action by which these agents improved insulin sensitivity. However, as has been reported widely in the literature, PPARγ is now recognized to be responsible for the dose-limiting, off-target side effects associated with currently available insulin sensitizers.

In 2010, MSDC scientists made the breakthrough discovery that a key protein complex located at the crossroads of metabolism in the inner mitochondrial membrane, called mTOT, is the mechanism of action through which insulin sensitizers produce their anti-diabetic effects. As a result of this key insight, and as demonstrated in multiple clinical studies in patients diagnosed with type 2 diabetes, MSDC and its collaborators have shown that mTOT is the molecular complex through which insulin sensitization is achieved.

MSDC’s two novel insulin sensitizers, MSDC-0160 and MSDC-0602 have completed Phase 2 clinical studies and form the foundation of a new class of insulin sensitizing compounds called mTOT Modulators™.