The Efficacy and Tolerability of Exenatide in Comparison to Placebo; a Systematic Review and Meta-analysis of Randomized Clinical Trials

Recent investigations in finding new drugs in the treatment of diabetes have led to the discovery of several pathological pathways involved in diabetes. Exenatide a drug with incretin mimetic activity was studied in several in vivo and in vitro as well as human studies. It has shown promising results in controlling metabolic indices in type-2 diabetes and was approved by FDA but still there is an active safety alert on it. In this study we aimed to meta-analyze all placebo-controlled clinical trials on the efficacy or tolerability of exenatide in type 2 diabetes. The literature search provided 1016 articles while only 14 articles were eligible to be included in the meta-analysis with a total of 2583 patients enrolled in the study. According to the wide variation in design of various studies, the study duration of 16 weeks and less or more and dose (5 μg bid versus 10 μg bid) were considered and analyzed. The results of this meta-analysis show that exenatide decreases fasting plasma glucose and HbA1C significantly regardless of dose and study duration. The effect of exenatide on weight reduction was more prominent at the dose of 10 μg bid regardless of the study duration, however at the dose of 5 μg bid, significant results were observed after drug administration for more than 16 weeks. Exenatide usage decreased serum triglycerides indifferent to dose and study duration while its effect on cholesterol was not prominent. Along with these impacts, exenatide changed LDL and HDL cholesterol at the lower dose. The hemodynamic effect of exenatide was observed as significant decrements in systolic and diastolic blood pressure at the higher dose. The risk of nausea, vomiting and hypoglycemia was significant and indifferent to dose while headache and nasopharyngaitis were seen more at lower dose. It is concluded that exenatide can be considered as a good hypoglycemic agent in type-2 diabetic patients with benefits on lipid profile and blood pressure with partially questionable tolerability.