Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes

Abstract

The risks of cardiovascular disease (CVD) and type 2 diabetes increase as body mass index increases in overweight (25-30 kg/m 2 ) and obese (430 kg/m 2 ) individuals. However, these risks can be reduced with even modest weight loss. In patients with established type 2 diabetes, control of both glycemia and body weight are important to minimize the risk of future diabetic complications. Exenatide is a 39-amino-acid peptide incretin mimetic currently approved in the United States for the treatment of type 2 diabetes as an adjunct to sulfonylurea and/or metformin. Phase-3 clinical studies showed exenatide therapy for 30 weeks significantly reduced glycosylated hemoglobin (HbA1c), and fasting and postprandial plasma glucose, while significantly reducing body weight. Open-label extensions from these pivotal trials demonstrated patients treated with exenatide for 2 years had sustained reductions in glycemic control at 30 weeks and a progressive reduction in body weight. Patients treated with exenatide also had improvement in blood pressure, inflammatory markers, and lipid profiles. The glucoregulatory and weightreducing effects of exenatide are the result of multiple modes of action that mimic several of the glucoregulatory actions of the naturally occurring peptide, glucagon-like peptide-1 (GLP-1). These include restoration of first phase insulin response, enhancement of glucose-dependent insulin secretion, suppression of inappropriate glucagon secretion, slowing of gastric emptying, and affects on satiety leading to reduced food intake. Further research is required to fully understand the role for exenatide to potentially alleviate metabolic disorders associated with type 2 diabetes, including CVD and obesity. Drug Dev. Res. 67:666-676, 2006.

Preparation, Characterization, and Pharmacodynamics of Exenatide-Loaded Poly(DL-lactic-co-glycolic acid) Microspheres

“…[3][4][5] Since these actions all contribute to the reduction in fasting and postprandial blood glucose in patients with type 2 diabetes mellitus without inducing hypoglycemia, exenatide has been approved by US FDA as an adjunctive treatment in patients unable to achieve adequate glucose control using metformin and/or sulfonylurea, with subcutaneous administration twice daily. 6) However, frequent injections are inconvenient for the patients, so the development of sustained-release delivery system would be beneficial.…”