Abstract
Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adamantane / administration & dosage
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Adamantane / adverse effects
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Adamantane / analogs & derivatives*
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Adamantane / therapeutic use
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Adenosine Deaminase Inhibitors*
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Clinical Trials as Topic
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Diabetes Mellitus, Type 2 / drug therapy*
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Dipeptidyl Peptidase 4
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Dipeptidyl-Peptidase IV Inhibitors*
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Drug Administration Schedule
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Exenatide
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Glucagon-Like Peptide 1 / administration & dosage
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Glucagon-Like Peptide 1 / adverse effects
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Glucagon-Like Peptide 1 / analogs & derivatives*
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Glucagon-Like Peptide 1 / biosynthesis
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Glucagon-Like Peptide 1 / classification
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Glucagon-Like Peptide 1 / physiology*
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Glucagon-Like Peptide 1 / therapeutic use
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Glucagon-Like Peptide-1 Receptor
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Glycoproteins / antagonists & inhibitors*
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Humans
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Hypoglycemic Agents* / administration & dosage
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Hypoglycemic Agents* / adverse effects
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Hypoglycemic Agents* / therapeutic use
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Liraglutide
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Nitriles
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Peptides / administration & dosage
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Peptides / adverse effects
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Peptides / therapeutic use*
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Pyrazines / administration & dosage
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Pyrazines / adverse effects
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Pyrazines / therapeutic use*
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Pyrrolidines
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Receptors, Glucagon / agonists*
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Sitagliptin Phosphate
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Triazoles / administration & dosage
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Triazoles / adverse effects
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Triazoles / therapeutic use*
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Venoms / administration & dosage
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Venoms / adverse effects
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Venoms / therapeutic use*
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Vildagliptin
Substances
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Adenosine Deaminase Inhibitors
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Dipeptidyl-Peptidase IV Inhibitors
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GLP1R protein, human
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Glucagon-Like Peptide-1 Receptor
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Glycoproteins
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Hypoglycemic Agents
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Nitriles
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Peptides
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Pyrazines
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Pyrrolidines
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Receptors, Glucagon
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Triazoles
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Venoms
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Liraglutide
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Glucagon-Like Peptide 1
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Exenatide
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DPP4 protein, human
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Dipeptidyl Peptidase 4
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Vildagliptin
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Adamantane
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Sitagliptin Phosphate