title: 11β-HSD1 inhibitors for the treatment of type 2 diabetes and cardiovascular disease.
abstract: Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, 11β-HSD1 inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11β-HSD1 inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors.
authors.affiliation: University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Anderson
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007113:Immunity, Innate / Q000187:drug effects; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D058990:Molecular Targeted Therapy / Q000009:adverse effects
chemical_list: D000959:Antihypertensive Agents; D015507:Drugs, Investigational; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human