When compared head-to-head in patients with type 2 diabetes mellitus, five once-weekly glucagonlike peptide–1 receptor agonists yield appreciably different effects on hemoglonin A1c (HbA1c) fasting plasma glucose, body weight, and nausea but very similar effects on hypoglycemia, blood pressure, lipids, and C-reactive protein levels, according to a report published online Dec. 7 in Annals of Internal Medicine.
Until now, no studies have directly compared the efficacy and safety of various glucagonlike peptide–1 receptor agonists (GLP-1RAs) for patients with type 2 diabetes. To do so, researchers performed a network meta-analysis of 34 randomized controlled trials of at least 6 months’ duration involving a total of 21,126 patients and comparing albiglutide, dulaglutide, exenatide, semaglutide, or taspoglutide against either placebo or another glucose-lowering agent. All the trials were published between 2008 and 2015, said Dr. Francesco Zaccardi of the Diabetes Research Centre, Leicester (England) General Hospital and his associates.
Taken together, the five once-weekly GLP-1RAs reduced the primary outcome measure, hemoglobin A1c, compared with placebo. Dulaglutide produced the greatest reduction (1.4%). All the agents also significantly reduced fasting plasma glucose, compared with placebo, with exenatide producing the greatest reduction. Exenatide, semaglutide, and higher doses of dulaglutide and taspoglutide also significantly reduced body weight by between 0.7 kg and 1.3 kg, compared with placebo. “Our results would therefore suggest clinically significant differences on three key indicators of metabolic control,” Dr. Zaccardi and his associates said (Ann. Intern. Med. 2015 Dec. 7. doi: 10.7326/M15-1432).
The risk for nausea also differed among the five agents. Taspoglutide carried the highest risk, which ranged from two- to ninefold higher than that of the other GLP-1RAs. With taspoglutide the risk for nausea was more than eight times higher than that with albiglutide.
Conversely, the risks for symptomatic hypoglycemia and rates of beneficial changes in blood pressure, lipid profiles, and C-reactive protein levels were similar across the five GLP-1RAs.
This meta-analysis was supported by an unrestricted grant from Sanofi-Aventis to the University of Leicester, and by the National Institute for Health Research and University Hospitals of Leicester and Loughborough University. Dr. Zaccardi reported having no relevant financial disclosures other than funding from Sanofi-Aventis; his associates reported ties to numerous industry sources, including the manufacturers of the five GLP-1RAs analyzed here.