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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
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Allylamine / analogs & derivatives
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Allylamine / pharmacology
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Allylamine / therapeutic use
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Anticholesteremic Agents / pharmacology
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Anticholesteremic Agents / therapeutic use
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Bariatric Surgery
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Bile Acids and Salts
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Cardiovascular System / drug effects
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Colesevelam Hydrochloride
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Comorbidity
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / physiopathology
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Dipeptidyl-Peptidase IV Inhibitors / pharmacology
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Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
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Exenatide
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Glucagon-Like Peptide 1 / analysis
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Glucokinase / physiology
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Humans
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Hyperglycemia / physiopathology
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / therapeutic use*
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Indoles / pharmacology
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Indoles / therapeutic use
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Insulin / pharmacology
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Insulin Resistance / physiology
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Insulin-Secreting Cells / drug effects
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Insulin-Secreting Cells / physiology
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Liver / drug effects
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Liver / physiopathology
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Obesity / epidemiology
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Obesity / surgery
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Peptides / administration & dosage
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Randomized Controlled Trials as Topic
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D2 / drug effects
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Sodium-Glucose Transporter 2 Inhibitors
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Treatment Outcome
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Venoms / administration & dosage
Substances
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Anticholesteremic Agents
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Bile Acids and Salts
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Dipeptidyl-Peptidase IV Inhibitors
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Hypoglycemic Agents
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Indoles
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Insulin
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L 783281
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Peptides
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Receptors, Dopamine D2
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Sodium-Glucose Transporter 2 Inhibitors
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Venoms
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Allylamine
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Glucagon-Like Peptide 1
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Exenatide
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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Glucokinase
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Colesevelam Hydrochloride