GLP-1 medications have been viewed as a sort of “wonder drug,” as they have been found to improve insulin release, treat diabetes, reduce blood sugar levels and promote weight loss. But scientists are still grasping what allows for those health benefits.

Researchers at the Salk Institute for Biological Studies in La Jolla examined that topic in a new study published March 4 in the Proceedings of the National Academy of Sciences. They concluded that part of a protein complex called Mediator plays a key role in making GLP-1 drugs impactful.

GLP-1 drugs come in brand names such as Ozempic, Wegovy and Mounjaro.

The study, funded by a combination of grants from the U.S. National Institutes of Health and private donors, sought to explore how GLP-1 drugs (short for glucagon-like peptide-1 receptor agonists) can make pancreatic beta cells more viable and stress-resistant.

Along the way, they found that a protein named Med14 can enable gene expression changes and lead to positive health impacts.

The discovery comes from a research team consisting of senior author Dr. Marc Montminy, a biochemist, physiologist and distinguished professor emeritus at the Salk Institute; first author Sam Van de Velde, a staff scientist in Montminy’s lab; and Rueben Shaw, a professor and director of the National Cancer Institute-designated Salk Cancer Center.

Van de Velde explained the group’s findings to the La Jolla Light.

“We basically discovered a small molecular switch,” he said of Med14. “When the cells in the pancreas that make and secrete insulin, which are beta cells … are exposed to GLP-1 drugs … the switch gets turned on. …

“This leads to activation of hundreds of genes simultaneously over time. So this gene activation … allows beta cells to make more insulin and be healthier in conditions where the need for insulin increases.”

GLP-1 drugs mimic hormones made in the body naturally. According to the institute, attaching to corresponding GLP-1 receptors on pancreatic cells allows GLP-1 hormones to produce and release insulin into the body.

The findings open the door for further exploration, and Van de Velde said that starts at the molecular level.

“The hope is that if you do that, it will then pave the way for a new generation of therapies that could be even more effective or more specific … for where they act on your body,” he said.

Van de Velde said he sees potential in several different aspects of GLP-1 drugs.

“There’s great interest … in the field for knowing where in humans the receptor for these drugs exactly is … in our body,” he said.

“One place to take it next is to figure out how our findings really translate to human biology. Because we, of course, use rodent models [and] cells that we grow in petri dishes in the lab … but it’d be a good next step to know how this works in humans.” ♦