Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs), new therapeutic agents for the treatment of type 2 diabetes, have shown promise in the reduction of hemoglobin A1c (HbA1c) levels, fasting plasma glucose levels, and body weight, according to a systematic review and network meta-analysis published in the January 19 issue of the Annals of Internal Medicine. 


Senior author Melanie J. Davies, MD, and fellow investigators analyzed 34 randomized, controlled trials (21,126 participants; ≥24 weeks of follow-up) of albiglutide, dulaglutide, once-weekly exenatide, semaglutide, and taspoglutide. They found that all once-weekly GLP-1RAs reduced HbA1c and fasting plasma glucose, when compared with placebo. Compared with other once-weekly GLP-1RAs, dulaglutide (1.5 mg), once-weekly exenatide, and taspoglutide (20 mg) showed a greater reduction of HbA1c levels, fasting plasma glucose levels, and body weight. Taspoglutide, once-weekly exenatide, and dulaglutide reduced body weight, when compared with placebo. 


Among the drugs, differences found in blood pressure, blood lipid levels, and C-reactive protein levels were clinically insignificant. Once-weekly exenatide increased heart rate, compared with albiglutide and dulaglutide (1.4 to 3.2 beats/min). Taspoglutide had the highest risk for nausea. The risk for hypoglycemia among the once-weekly GLP-1RAs studied was similar. 


The study was limited by poor data on semaglutide, and the definitions of outcomes varied among the trials in the analysis, the authors said.