GLP-1 Receptor Agonists vs Other Anti-Diabetics

A newly published meta-analysis using data from 78 trials showed that most glucagon-like peptide (GLP)-1 receptor agonists effectively lowered glycemic levels in patients with type 2 diabetes, and also decreased the rate of hypoglycemia compared with treatment with insulin.

“The network meta-analysis based on Bayesian model makes indirect comparison among multiple treatments available, especially when there are few trials for direct comparison between different anti-diabetic drugs, such as comparisons between dulaglutide and insulin in our study,” wrote researchers led by Zhixia Li, Peking University Health Science Center, Beijing, China. “Network meta-analysis has been proved to be the most appropriate method for multiple treatments comparison to date.”

For the study, the researchers conducted a systematic review of literature comparing GLP-1 receptor agonists with placebo or other traditional anti-diabetes treatments in patients with type 2 diabetes. They used data from 78 trials including 13 treatments (seven GLP-1 receptor agonists) to calculate odds ratios [ORs] for incidence of hypoglycemia, treatment discontinuation, and achievement of HbA1c goals. The studies were published between 2004 and 2014. The results were published in PLOS One.

All of the GLP-1 receptor agonists in the studies were found to increase the risk for hypoglycemia compared with placebo except for albiglutide. However, compared with insulin and sulphonylureas, all of the GLP-1 receptor agonists decreased the risk for hypoglycemia with the exception of dulaglutide.

A higher proportion of patients were found to discontinue treatment when treated with exenatide (OR=3.11), liraglutide (OR=3.48), lixisenatide (OR=1.78) and taspoglutide (OR=5.43) compared with placebo, insulin, or sitagliptin.

The researchers listed two reasons why this increase may occur.

“Firstly, all GLP-1 receptor agonists are injected subcutaneously, and cannot be administered orally. The incidence of treatment discontinuation among patients who had injection site adverse events was high,” the researchers wrote. “Secondly, the adverse events of GLP-1 receptor agonists like nausea, diarrhea, and vomiting, also account for the incidence of treatment discontinuation. Especially for the most commonly occurred nausea, which usually lasts a long time, is a tough experience for type 2 diabetics to bear.”

Looking at glycemic levels, the researchers found that compared with placebo, patients assigned to any of the GLP-1 receptor agonists in the studies had decreases in levels. Additionally, compared with sitagliptin and insulin, dulaglutide, exenatide long-acting release, liraglutide, and taspoglutide significantly lowered HbA1c.

Li Z, Zhang Y, Quan X, et al. Efficacy and acceptability of glycemic control of glucagon-like peptide-1 receptor agonists among type 2 diabetes: a systematic review and network meta-analysis. PLoS One. Epub 2016 May 9.