Exenatide Twice Daily: A Review of Its Use in the Management of Patients with Type 2 Diabetes Mellitus

Abstract

Exenatide, administered subcutaneously twice daily (Byetta(®)), is a synthetic version of the natural peptide exendin-4, which is a glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic). Exenatide binds to the GLP-1 receptor with the same affinity as GLP-1, but has a much longer half-life, since it is not degraded by the enzyme dipeptidyl peptidase-4. Exenatide twice daily enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, slows gastric emptying and reduces caloric intake. In well-designed clinical trials, adjunctive subcutaneous exenatide 5 or 10 μg twice daily for 16-52 weeks significantly and dose-dependently improved glycaemic control and reduced mean body weight compared with placebo in patients with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs (OADs) and/or basal insulin. The improvements in glycaemic control and reductions in body weight were stably maintained during long-term therapy (up to 3.5 years). The efficacy of adjunctive exenatide twice daily was generally similar to that of basal, prandial or biphasic insulin, sulfonylureas, rosiglitazone and lixisenatide, and less than that of liraglutide, taspoglutide or exenatide once weekly with respect to reductions in glycated haemoglobin. Exenatide twice daily was generally well tolerated; mild to moderate nausea and vomiting, which decreased with time on therapy, were the most common adverse events. In patients not receiving concomitant sulfonylureas or insulin, the incidence of hypoglycaemia was low; when it did occur, it was generally mild in severity. Thus, adjunctive exenatide twice daily is a valuable option in the treatment of type 2 diabetes inadequately controlled with OADs and/or basal insulin.

Adverse Effects of GLP-1 Receptor Agonists

“…It enhances insulin secretion from pancreatic β-cells, and decreases glucagon release from pancreatic α-cells [16]. GLP-1 receptor agonists are useful, injectable drugs for the treatment of T2D as they improve glycemic control and atherosclerosis-related parameters [17][18][19][20][21][22][23][24][25][26]. Short-acting GLP-1 receptor agonists primarily slow gastric emptying, and thus exert their main effect on postprandial blood glucose levels.…”

Vomiting as Common Adverse Event of Exenatide: A Case of Diabetic Patient with Type 2 and Duodenal Bulb and Gastric Ulcers who Showed Severe Vomiting Increased Gradually after Exenatide Injections

“…We first believed the patient's vomiting reflected the most commonly adverse event of exenatide administered [1,2]. However, the degree of vomiting did not decrease with time, but gradually worsened with 8 points on the STAS-J.…”

“…However, the adverse event of exenatide usually decreases with time [1,2]. We report a patient with T2DM and duodenal bulb and gastric ulcers, when she developed increased vomiting gradually after treatment with a usual dose of exenatide.…”

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

“…However, because most of these GLP-1 receptor agonists are at least partially eliminated by the kidneys, some limitations have been pointed out in presence of CKD [27]. Based on the current evidence, exenatide is eliminated by renal mechanisms [89] and should not be given in patients with severe CKD or ESRD [90]. Liraglutide is not eliminated by renal or hepatic mechanisms, but it should be used with caution since there are only limited data in patients with CKD [91].…”