11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Type 2 Diabetes

The document from 2010 examined the potential of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors as a treatment for type 2 diabetes (T2D). It noted that obesity and T2D were becoming increasingly common, affecting 170 million people globally. 11β-HSD1 plays a role in increasing local glucocorticoid levels, which is linked to obesity and metabolic issues. Studies in rodents indicated that inhibiting 11β-HSD1 could improve insulin sensitivity and metabolic health, while overexpression had the opposite effect. Early human trials with inhibitors like PF-915275 and INCB13739 showed improved glycemic control and hepatic insulin sensitivity, with no major side effects. However, there were concerns about the long-term effects on the hypothalamic-pituitary-adrenal axis and adrenal androgen production. The document concluded that despite the promise shown by 11β-HSD1 inhibitors, more extensive clinical trials were necessary to confirm their safety and effectiveness.