Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia

A relatively recent addition to the arsenal of antidiabetic drugs used for the treatment of type 2 diabetes mellitus (T2DM) has been the “incretin mimetics,” a group of drugs that work on the glucagon-like peptide-1 (GLP-1) receptor and enhance insulin secretion from the pancreatic β-cells in a glucose-dependent manner, more potently in hyperglycemic conditions, while suppressing glucagon secretion at the same time. Therefore, it was assumed that this class of drugs would have a lower risk of hypoglycemia than insulin secretagogues like sulphonylureas. However, GLP-1 receptor agonists have been proposed to cause hypoglycemia in healthy normoglycemic subjects implying that their action is not as glucose-dependent as once thought. Other studies concluded that they might not induce hypoglycemia and the risk is dependent on other individual factors. However, the FDA announced that the 12 GLP-1 receptor agonists currently available on the market had potential safety signs and evaluated the need for regulatory action. This review provides an overview of the studies that investigated the possible hypoglycemic effect of GLP-1 receptor agonists. In addition, the current review describes other adverse effects of GLP-1 receptor agonist treatment.

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The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes

Endocrinology and Metabolism ◽

10.3803/enm.2019.34.2.106 ◽

2019 ◽

Vol 34 (2) ◽

pp. 106 ◽

Cited By ~ 4

Author(s):

Gwang Sil Kim ◽

Joong Hyun Park ◽

Jong Chul Won

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Events ◽

Receptor Agonists ◽

Sodium Glucose Cotransporter ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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The Role of the Pharmacist in Managing Type 2 Diabetes with Glucagon-Like Peptide-1 Receptor Agonists as Add-On Therapy

Advances in Therapy ◽

10.1007/s12325-017-0491-1 ◽

2017 ◽

Vol 34 (3) ◽

pp. 638-657 ◽

Cited By ~ 1

Author(s):

Jerry Meece

Keyword(s):

Type 2 Diabetes ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Mechanisms of neuroprotective action of incretin mimetics

Diabetes Mellitus ◽

10.14341/dm7192 ◽

2016 ◽

Vol 19 (1) ◽

pp. 16-23 ◽

Cited By ~ 1

Author(s):

Timur Dmitrievich Vlasov ◽

Anna Vladimirovna Simanenkova ◽

Svetlana Vladimirovna Dora ◽

Evgeniy Vladimirovich Shlyakhto

Keyword(s):

New Drugs ◽

Brain Ischaemia ◽

Neuroprotective Effects ◽

Incretin Mimetics ◽

Receptor Agonists ◽

Cardioprotective Effects ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Antioxidant Effects

Recently, on the pharmacological market, new drugs from the class of incretin mimetics, or glucagon-like peptide-1 (GLP-1) receptor agonists, which have proven their high effectiveness in type 2 diabetes mellitus therapy, have appeared. At present, much attention has been paid to the pleotropic effects of incretin mimetics. In a number of both experimental and clinical studies, cardioprotective effects of this medication group have been demonstrated. The present review elucidates existing data about neuroprotective effects of GLP-1 receptor agonists in brain ischaemia and in nonischaemic nervous system diseases such as diabetic neuropathy and neurodegenerative disorders. The possible mechanisms for these effects, which appear to be primarily antioxidant effects, anti-inflammatory effects, antiapoptotic effects and an increase in neurons differentiation, are discussed.

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An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

Mediators of Inflammation ◽

10.1155/2013/591056 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Alessandra Puddu ◽

François Mach ◽

Alessio Nencioni ◽

Giorgio Luciano Viviani ◽

Fabrizio Montecucco

Keyword(s):

Type 2 Diabetes ◽

Cell Function ◽

Glucagon Secretion ◽

Advanced Glycation ◽

Chronic Hyperglycemia ◽

Gut Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreaticβ-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

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