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Glucagon-like polypeptide agonists in type 2 diabetes mellitus: efficacy and tolerability, a balance
Author(s) -
Sri Harsha Tella,
Marc Rendell
Publication year - 2015
Publication title -
therapeutic advances in endocrinology and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 30
eISSN - 2042-0196
pISSN - 2042-0188
DOI - 10.1177/2042018815580257
Subject(s) - medicine , liraglutide , weight loss , exenatide , hypoglycemia , type 2 diabetes , diabetes mellitus , insulin , gastric emptying , endocrinology , tolerability , glucagon like peptide 1 receptor , type 2 diabetes mellitus , discontinuation , adverse effect , agonist , obesity , receptor , stomach
Glucagon-like polypeptide (GLP-1) receptor agonist treatment has multiple effects on glucose metabolism, supports the β cell, and promotes weight loss. There are now five GLP-1 agonists in clinical use with more in development. GLP-1 treatment typically can induce a lowering of hemoglobin A1c (HbA1c) of 0.5–1.5% over time with weight loss of 2–5%. In some individuals, a progressive loss of weight occurs. There is evidence that GLP-1 therapy opposes the loss of β cells which is a feature of type 2 diabetes. The chief downside of GLP-1 treatment is the gastrointestinal motility disturbance which is one of the modes of action of the hormone; significant nausea, vomiting, and diarrhea may lead to discontinuation of treatment. Although daily injection of GLP-1 agents is successful, the development of extended release preparations allows for injection once weekly, and perhaps much longer in the future. The indication for GLP-1 use is diabetes, but now, liraglutide has been approved for primary treatment of obesity. When oral agents fail to control glucose levels in type 2 diabetes, there is a choice between long-acting insulin and GLP-1 agonists as additional treatments. The lowering of HbA1c by either modality is equivalent in most studies. Patients lose weight with GLP-1 treatment and gain weight on insulin. There is a lower incidence of hypoglycemia with GLP-1 therapy but a much higher incidence of gastrointestinal complaints. Insulin dosing is flexible while GLP-1 agents have historically been administered at fixed dosages. Now, the use of combined long-acting insulin and GLP-1 agonists is promising a major therapeutic change. Combined therapy takes advantage of the benefits of both insulin and GLP-1 agents. Furthermore, direct admixture of both in the same syringe will permit flexible dosing, improvement of glucose levels, and reduction of both hypoglycemia and gastrointestinal side effects.

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