Effects of exenatide on metabolic parameters/control in obese Japanese patients with type 2 diabetes

Abstract

ExEnatidE is a human glucagon-like peptide-1 (GLP-1) receptor agonist produced by solid-phase peptide synthesis that has the same amino acid sequence as exendin-4, which was isolated from the saliva of the Gila monster (Heloderma suspectum). Similar to endogenous active GLP-1, exenatide specifically binds to GLP-1 receptors (seven-transmembrane, G proteincoupled receptors) and activates adenylate cyclase to increase the intracellular concentration of cyclic AMP in β-cells, leading to a decrease in plasma glucose levels by promoting glucose-dependent insulin secretion. In addition to the suppression of increased glucagon secretion, exenatide promotes weight loss caused by delayed gastric emptying and/or suppression of food Effects of exenatide on metabolic parameters/control in obese Japanese patients with type 2 diabetes , Jun-ichiro Miyagawa 1) and Mitsuyoshi Namba abstract. The effects of exenatide on glycemic control, lipid metabolism, blood pressure, and gastrointestinal symptoms were investigated in obese Japanese patients with type 2 diabetes mellitus. Twenty-six outpatients were enrolled and administered 5 μg of exenatide twice daily. If there was insufficient weight loss and/or insufficient improvement in glycemic control, the dose was increased to 10 μg twice daily. Follow-up was continued until the 12 th week of administration. Hemoglobin A1c, glycoalbumin, fasting plasma glucose, body weight, fasting serum C-peptide, serum lipids, blood pressure, and pulse rate were measured before and after the observation period. In the initial phase of exenatide therapy, each patient received a diary to record gastrointestinal symptoms. During treatment with exenatide, hemoglobin A1c decreased significantly and serum C-peptide increased significantly. Body weight, low-density lipoprotein cholesterol, and systolic blood pressure decreased significantly. Nausea was the most frequent gastrointestinal symptom and occurred in 16 patients. Its onset was noted at a mean of 1.7 h after injection, the mean duration was 1.1 h, and it continued for a mean of 9.3 days after the initiation of administration. Patients with nausea showed a significant decrease in hemoglobin Alc, glycoalbumin, or body weight compared with those without nausea. These findings suggest that a more marked improvement in metabolic parameters by exenatide can be partly dependent on the manifestation of gastrointestinal symptoms.

Actions of PGLa-AM1 and its [A14K] and [A20K] analogues and their therapeutic potential as anti-diabetic agents

“…As well as lowering blood glucose levels by stimulating insulin secretion, GLP-1 exerts other beneficial effects on glucose homeostasis by suppression of appetite, reduction in plasma glucagon concentrations, and improvement of glucose uptake in peripheral tissues. In addition, GLP-1 [39,40] and GLP-1 receptor agonists [41,42] stimulate β-cell proliferation and regeneration, and protect against β-cell damage leading to increased β-cell mass and improved βcell function. This study has shown that [A14K]PGLa-AM1 shows beta-cell proliferative activity comparable to that of GLP-1 when tested in BRIN-BD11 cells and is equally effective in protecting the cells against cytokine-induced apoptosis (Fig 8).…”

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.…”

Lipid Effects and Cardiovascular Disease Risk Associated with Glucose-Lowering Medications

“…While GLP-1 agonists have been shown to significantly reduce body weight and blood pressure in both animal models and clinical studies [80,86,87], data on DPP-4 inhibitors are less consistent [88,89]. In most studies, favorable effects of incretin-based therapies on lipid parameters were reported, including decreased triglyceride, total cholesterol, and LDL cholesterol levels, along with reduced apolipoprotein-B48 concentrations [90][91][92][93]. Initial randomized trials and meta-analyses did not observe any detrimental effect of incretin-based therapies and suggested even a lower risk of cardiovascular events in comparison with conventional anti-diabetic agents [94][95][96][97].…”