S-707106

S-707106 is an orally available small molecule insulin sensitizer developed by Shionogi for the treatment of type 2 diabetes mellitus and metabolic disorders. It acts primarily as a selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that converts inactive cortisone to active cortisol, thereby regulating local glucocorticoid activity. By inhibiting 11β-HSD1, S-707106 reduces tissue-specific cortisol generation, which can improve insulin sensitivity and have beneficial effects on glucose metabolism, body composition (reducing fat mass and increasing muscle mass), and potentially obesity-related parameters. There is also evidence suggesting it may inhibit diacylglycerol acyltransferase 1 (DGAT1), involved in triglyceride synthesis[4][5][6]. Clinical studies have evaluated its efficacy in patients with type 2 diabetes mellitus as well as those with Cushing’s syndrome or autonomous cortisol secretion who have impaired glucose tolerance[2][3][5][6]. While some trials did not meet their primary endpoints for glycemic improvement, secondary benefits were observed in subgroups with higher BMI or metabolic risk factors.