A new meta-analysis found little difference in the performance of five once-weekly type 2 diabetes medications, although small differences in side effects surfaced.

British researchers writing in the journal Annals of Internal Medicine concluded that there was no clear winner among once-a-week glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating the prevalent condition.

For instance, exenatide and dulaglutide tended to work better than the rest in glucose control and body weight reduction – but with typically small differences. Many other outcomes yielded no difference.

Lead investigator Dr. Francesco Zaccardi of the University of Leicester said their study,  which was published online on Dec. 8, was the first to directly compare the once-weekly class of diabetes drugs.

“Its aim is to assist decision makers in providing patient-centered care by balancing the potential risks and benefits of individual drugs within the class,” the research team says.

The research covered 34 clinical trials that involved over 20,000 patients, comparing dulaglutide, exenatide, taspoglutide, and albiglutide, and semaglutide.

The team found no substantial difference among the drugs’ impact on hypoglycemia, blood pressure, lipid status, and C-reactive proteins. In decreasing weight and HbA1c, a measure of average blood sugar over around three months, dulaglutide, exenatide, and taspoglutide outperformed albiglutide and semaglutide – but with small differences.

Dr. Sethu Reddy, chief of the Adult's Diabetes Section at Boston’s Joslin Diabetes Center who was not involved in the research, dubbed the weight loss instructive.

"[A] lot of people hear stories of people losing a lot of weight, but the mean weight loss is modest," he said.

As for the risk of nausea, taspoglutide 20 mg was on top, while exenatide raised heart rate by 1.4 to 3.2 beats per minute compared to albiglutide and dulaglutide.

Reddy cautioned that the results were based on comparisons of existing data from different studies, meaning there were no trials comparing the drugs to one another. The researchers noted that they were unable to find published data comparing Novo Nordisk's semaglutide to any of the other drugs mentioned, adding that there may have been a possibility of bias. 

He added, however, that the existing studies showed which drugs work to lower blood sugar and manage other diabetes symptoms.

"That makes me more comfortable that this therapeutic area is real, and not a flash in the pan and the mechanism is real," Reddy said.

In an accompanying editorial, Dr. Victor Montori noted that the studies in the meta-analysis were industry-funded and not created for the purpose of better clinical decision-making.

"Companies design, conduct, and report research to enter the market and position their product favorably within the class ... Often, the available evidence does not provide a useful estimate of differences within the drug class," he explained, calling for the claims of differences to be met with skepticism.

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