Leicester, UK—Because once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are relatively new drugs for the treatment of type 2 diabetes, pharmacists get a lot of questions about their effectiveness and potential adverse effects.
A review recently published in the Annals of Internal Medicine helps arm them with some answers, although an accompanying commentary condemns the lack of high-quality information.
Researchers from the Diabetes Research Centre at the University of Leicester sought to summarize evidence for the cardiometabolic efficacy and adverse effects of once-weekly GLP-1RAs in adults with type 2 diabetes.
For the industry-sponsored review, the researchers searched databases through September 26, 2015, for randomized, controlled trials looking at albiglutide, dulaglutide, once-weekly exenatide, semaglutide, and taspoglutide, which also reported a cardiometabolic outcome, hemoglobin A1c (HbA1c) or safety outcome.
Based on 34 trials involving 21,126 participants, study authors found that, compared with placebo, all once-weekly GLP-1RAs reduced HbA1c and fasting plasma glucose. In addition, taspoglutide 20 mg, once-weekly exenatide, and dulaglutide 1.5 mg were found to reduce body weight.
On the other hand, clinically marginal or no differences were found for blood pressure, blood lipid levels, and C-reactive protein levels.
In terms of adverse effects, study authors report that once-weekly exenatide increased heart rate compared with albiglutide and dulaglutide (1.4 to 3.2 beats/min). Among once-weekly GLP-1RAs, the risk for hypoglycemia was similar, whereas taspoglutide, 20 mg, had the greatest risk for nausea—odds ratios, 1.9 to 5.9.
“Compared with other once-weekly GLP-1RAs, dulaglutide, 1.5 mg; once-weekly exenatide; and taspoglutide, 20 mg, showed a greater reduction of HbA1c, fasting plasma glucose, and body weight,” the researchers conclude. “Taspoglutide, 20 mg, had the highest risk for nausea; risk for hypoglycemia among once-weekly GLP-1RAs was similar.”
An accompanying editorial from Victor M. Montori, MD, MSc, and Rene Rodriguez-Gutierrez, MD, of the Mayo Clinic decried the lack of information allowing insightful comparison of antihyperglycemic agents.
“Data on outcomes of importance to patients, including quality of life, treatment burden and morbidity and mortality, were sparse or nonexistent,” Montori and Rodriguez-Gutierrez write. “Because of the low reliability of the evidence summarized (7), claims of differences between agents should be met with skepticism, including rankings that suggest that, within the once-weekly preparations, exenatide and dulaglutide are associated with the biggest reduction in hemoglobin A1c, level and weight, while being well-tolerated.”
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