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04-28-2020 | GLP-1 agonists | News

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Early findings suggest route to GLP-1 receptor agonism with less gastrointestinal discomfort

Author: Eleanor McDermid


medwireNews: A phase 1 study of a novel glycosylated Fc-fused glucagon-like peptide-1 receptor agonist (GLP-1-gFc) suggests it could deliver similar blood glucose-lowering efficacy but with fewer gastrointestinal side effects relative to existing medications in the class.

Young Sung (Genexine Co. Ltd, Seongnam, Republic of Korea) and study co-authors note that other long-acting GLP-1 receptor agonists, such as dulaglutide, are associated with gastrointestinal side effects from the very lowest doses.

But when tested in 48 healthy men, GLP-1-gFc “induced almost no nausea or vomiting” after one-off doses of 0.01–0.16 mg/kg, with just one person reporting nausea after receiving the 0.04 mg/kg dose. Four of six men who received the highest dose of 0.24 mg/kg reported transient nausea and one had transient vomiting.

GLP-1-gFc had “marked” glucose-lowering ability from the lowest dose in an oral glucose tolerance test, report the study authors. Three days after taking the medication, the area under the curve was suppressed by an average of 40.7% compared with at baseline, which the researchers say “is superior to the maximum 29%” reduction seen with dulaglutide in a phase 1 trial.

However, glucose-lowering efficacy at these lower GLP-1-gFc doses tended to be lost by day 5 and was maintained only at the highest dose.

And the team cautions that “it is uncertain whether these distinctive safety profiles of GLP-1-gFc would be reproduced in patients with type 2 diabetes, considering differences in physiological status and susceptibility to GLP-1 [receptor agonists]” compared with healthy people.

The study, which also details preclinical findings, is published in Diabetes, Obesity and Metabolism.

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

Diabetes Obes Metab 2020; doi:10.1111/dom.14058


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