Incretin-based Therapies (Glucagon-like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors) for the Treatment of Type 2 Diabetes (original) (raw)
2012, Canadian Journal of Diabetes
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The prevalence of diabetes and impaired glucose tolerance is predicted to dramatically increase over the next two decades. Clinical therapies for type 2 diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral anti-diabetic agents, and ultimately insulin initiation. In this report, we review the clinical trial results of two innovative T2DM treatment therapies that are based on the glucoregulatory effects of incretin hormones. Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. Additionally, incretin mimetics lower postprandial and fasting glucose, suppress elevated glucagon release, and are associated with progressive weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies in patients with T2DM have shown that DPP-4 inh...
Incretin System: Recent Advances in Glucagon Like Peptide-1 and Dipeptidyl Peptidase-4 Inhibitors
Journal of Patan Academy of Health Sciences, 2015
The endogenous incretins, glucose-dependent insulinotropic polypeptide and Glucagon-like peptide, are peptide hormones secreted from endocrine cells in the small intestine. Glucagon-like peptide-1 stimulates insulin and suppresses glucagon secretion, delays gastric emptying, and reduces appetite and food intake, which explains the positive effect of incretin mimetics on weight. The incretins have also been shown to have a sustained improvement in glycemic control over three years. A wide range of cardiovascular benefits have also been claimed, such as lowering of blood pressure and postprandial lipids. Clinical trials with the incretin mimetic exenatide and liraglutide show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with Glucagon-like peptide-1 receptor agonists is nausea, which lessens over time. Orally administered Dipeptidyl Peptidase-4 inhibitors reduce hemoglobin A1c by 0•5-1•0%, with few adverse effects and no weight gain. These new classes of anti-diabetic agents also expand β-cell mass in preclinical studies. However, long-term clinical studies are still needed to determine the benefits of incretin for the treatment of type 2 diabetes.
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