title: Management of type 2 diabetes: new and future developments in treatment.
abstract: The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium-glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11β-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.
authors.affiliation: Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: Abd A
authors.initials: AA
authors.lastname: Tahrani
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Bailey
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Barnett
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050110:Bariatric Surgery; D001647:Bile Acids and Salts; D002319:Cardiovascular System / Q000187:drug effects; D000069472:Colesevelam Hydrochloride; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000032:analysis; D005941:Glucokinase / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D009765:Obesity / Q000453:epidemiology / Q000601:surgery; D010455:Peptides / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; C119066:L 783281; D010455:Peptides; D017448:Receptors, Dopamine D2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014688:Venoms; D000499:Allylamine; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D005941:Glucokinase; D000069472:Colesevelam Hydrochloride