Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

Spanish

French

Background:

Long-acting glucagon-like peptide-1 receptor agonists (LA-GLP-1RAs) may deliver additional therapeutic benefits over other available incretin-based therapies.

Objective:

To pool results of randomized controlled trials comparing the efficacy and safely of maximum dose LA-GLP-1RAs (liraglutide, exenatide once weekly) with exenatide twice daily and dipeptidyl-peptidase-IV inhibitors in patients with type 2 diabetes.

Methods:

We searched PubMed, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE (all from inception-December 2010), and abstracts presented at the American Diabetes Association Scientific Sessions in 2009 and 2010 to identify English-language reports of studies of at least 24 weeks' duration. The primary endpoint was mean change in hemoglobin A_1c (A1C) from baseline to study endpoint. Weighted mean differences or odds ratios and their 95% confidence intervals for each outcome relative to control were calculated as appropriate.

Results:

A1C was reduced favoring LA-GLP-1RAs compared with exenatide twice daily and sitagliptin (weighted mean difference [WMD] –0.47% [95% CI –0.69 to –0.25] and WMD –0.60% [95% CI –0.75 to –0.45], respectively). Odds ratios greater than 1 favored LA-GLP-1RAs for reaching the A1C target goal of less than 7%. Fasting plasma glucose (FPG) was reduced and favored the LA-GLP-1RA–based regimens. Exenatide demonstrated significantly greater reductions in postprandial glucose (PPG) after the morning and evening meals, compared with LA-GLP-1RAs. Body weight was reduced similarly between LA-GLP-1RAs and exenatide, but favored LA-GLP-1RAs in the sitagliptin comparator trials. LA-GLP-1RA therapy was not associated with severe hypoglycemia or acute pancreatitis. Compared with exenatide twice daily, vomiting was reduced significantly with LA-GLP-1RAs (OR 0.55; 95% CI 0.34 to 0.89); there was a trend toward decreased nausea (OR 0.58; 95% CI 0.32 to 1.06) and no difference in the incidence of diarrhea (OR 1.03; 95% CI 0.67 to 1.58).

Conclusions:

Compared with other incretin-based therapies, LA-GLP-1RAs produce greater improvement in A1C and FPG. They provide lesser effect on PPG, similar reduction in body weight, and result in a potentially favorable adverse event profile compared with exenatide twice daily.

Keywords

dipeptidyl peptidase IV inhibitor exenatide glucagon-like peptide-1 incretins liraglutide sitagliptin type 2 diabetes

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