At the annual meeting of the Society for the Study of Ingestive Behavior, a leading international research conference for experts on eating behavior, one of the lead researchers, Dr. Bart De Jonghe of the University of Pennsylvania School of Nursing, highlighted their findings. The research team focused on reducing the most common side effect of nausea and vomiting, associated with glucagon-like peptide-1 (GLP-1) agents in up to 50% of patients who take these FDA-approved agents.
GLP-1 agents are effective in reducing hyperglycemia; however, due to these side effects, they are subject to significant nonadherence. Modification of exendin-4, the ingredient found in these agents, through the molecular attachment of vitamin B12 (cyanocobalamin) resulted in a conjugate compound that is not as readily absorbed into the areas of the brain responsible for triggering these emetogenic adverse effects.
“Drug regimens often have long lists of side effects which negatively impact treatment,” said De Jonghe, adding, “In type 2 diabetes, nausea and vomiting top that list. It’s the main reason people stop taking their diabetes medications, and diminishes quality of life for millions who do take them.”
Studying the exendin-4/B12 conjugate was challenging, however, and leaves much room for additional research because the studies were conducted on animals. Since standard study lab rats and mice are unable to vomit, the researchers used musk shrews, mouse-sized mammals with a vomiting reflex similar to humans’. The results demonstrated that although both versions of the drug demonstrated equal blood glucose control, vomiting occurred with only 12% of the shrews using the conjugate combination, whereas vomiting occurred in almost 90% of shrews dosed with ordinary exendin-4.
The experiments demonstrated that improvements in vomiting seen with the use of the conjugated compound were likely due to decreased activation of the dorsal vagal complex in the brain thought to be responsible for coordinating responses like vomiting to ensure survival.
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