Pharmacokinetic drug evaluation of exenatide for the treatment of type 2 diabetes

ABSTRACT

Introduction: Glucagon-like peptide-1 (GLP-1) receptor analogs are a group of therapeutic agents which mimic endogenous GLP-1, exerting their effect by the stimulation of the GLP-1 receptor with a wide distribution. Its activation increases insulin releasing dependent on blood glucose levels, suppression of glucagon secretion and a reduction of hepatic glucose output. It delays gastric emptying and increases satiety. Exenatide is the synthetic version of exendin-4, a natural peptide with similar properties to human GLP-1. There are two pharmaceutical forms, for subcutaneous injection: twice daily and once weekly.

Clinical practice guidelines recommend them because of a high efficacy reducing hyperglycemia, low risk of hypoglycemia and a significative weight loss effect. Gastrointestinal adverse events are the most common beside injection site-related. Their cost is the main limitation to use.

Areas covered: We review the recent literature investigating the pharmacokinetics and pharmacodynamics and efficacy-safety studies of exenatide twice daily and once weekly in type 2 diabetes

Expert opinion: GLP-1 receptor analogs are now positioned as an effective and safe drug for the treatment of type 2 diabetes. Exenatide significally reduces HbA1c and fasting plasma glucose. Additionally, it produces moderate weight loss and decreases blood pressure. One weekly formulation may improve compliance while cost is still a limitation. EXSCEL trial has shown that, despite cardiovascular safety, exenatide do not exhibits cardiovascular benefits.

KEYWORDS:

• Exenatide
• efficacy
• GLP1 receptor analogs
• hypoglycemia
• pharmacokinetics
• type 2 diabetes

Box 1. Drug summary

Acknowledgments

The authors thank all the subjects for their collaboration and thanks to Elsevier for assistance with the English language version of the manuscript. The clinical trials developed by Eli Lilly and Astra-Zeneca Company and subsequent publications form the basis for this review of the current data relevant to this novel antidiabetic drug. Astra-Zeneca was not involved in the writing of this article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The research group belongs to the ‘Centros de Investigación en Red’ of the ‘Instituto de Salud Carlos III’. This work was supported in part by grants from Instituto de Salud Carlos III and Consejería de Innovacion, Ciencia y Empresa de la Junta de Andalucía. This study has been co-funded by FEDER funds.