Mechanisms of Disease: Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 as a Novel Treatment for Metabolic Syndrome

The 2005 document reviews the potential of targeting 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to treat obesity and metabolic syndrome, based on the enzyme's role in tissue-specific cortisol production. Studies in obese patients and rodents suggest that inhibiting 11β-HSD1 could improve insulin sensitivity and prevent diabetes. Over 30 patents for selective inhibitors indicate pharmaceutical interest, but only a few may be clinically useful. Two inhibitors, BVT2733 and an unnamed adamantyl triazole from Merck, have shown promising results in rodents, significantly reducing fasting blood glucose, insulin levels, and lipids, and improving glucose tolerance without adverse liver effects. However, clinical trials are needed to confirm safety and efficacy in humans. The document highlights the importance of further research to establish 11β-HSD1 as a viable therapeutic target.