The popularity of Ozempic and Wegovy as diabetes and weight loss medications has skyrocketed. But how far would people go to avoid one of their major drawbacks—the need for weekly injections? A study out today shows it’s possible to genetically modify mice to make their own Ozempic-like drugs.
Scientists in Japan led the research, which involved gene-editing mice’s livers to produce an internal supply of exenatide, a first-generation GLP-1 drug. The edited mice were able to sustain levels of the drug for several months and experienced greater health improvements compared to controls. Similar gene therapies could possibly allow people to produce GLP-1s and other medications for life one day, the researchers say.
“This study suggests that genome editing could be used to create lasting treatments for complex diseases, potentially reducing the need for frequent medication,” the authors wrote in their paper, published Wednesday in Communications Medicine.
Semaglutide is the active ingredient in Ozempic and Wegovy. It’s part of the latest roster of GLP-1s, a drug class that’s now been around for 20 years. These drugs mimic the natural GLP-1 hormone, which regulates our hunger and insulin production, among other things. Newer agents like semaglutide are far more effective at helping people lose weight and control their blood sugar compared to diet and exercise alone.
One major reason why semaglutide is more effective than its earlier cousins is that it’s engineered to stay longer in the body, with its sustained effects lasting about a week. The original exenatide, by contrast, needed to be taken once or twice a day (a weekly extended-release formulation eventually replaced it, though both versions are now discontinued in the U.S.). A weekly injection schedule can still be difficult for some people to manage, however, which may help explain why many in the real world eventually stop using semaglutide and similar drugs (high costs and common gastrointestinal side effects being other important factors).
Pharmaceutical companies are working on longer-lasting formulations of GLP-1 drugs. The study researchers, based at the University of Osaka, are tinkering with a different approach, however. They argue that it’s possible to safely induce our cells to make certain drugs on their own, including GLP-1s, eliminating the need for continuous dosing completely.
In the study, the mice were first given high-calorie diets that made them obese and prediabetic. Using a CRISPR-based method, the researchers then inserted a gene into the liver cells of these mice with the instructions for making exenatide. As hoped, the treated mice produced levels of exenatide detectable in their blood for up to 28 weeks. Compared to untreated mice on the same diet, they also ate less food, gained less weight, and had improved insulin sensitivity. The treatment also appeared to be safe, with no noticeable side effects, such as interference with the mice’s production of natural GLP-1.
“We hope that our design of a one-time genetic treatment can be applied to many conditions that do not have exact genetic causes,” said senior study author Keiichiro Suzuki in a statement from the university.
The findings are, of course, only a proof of concept. Gene therapy is still in its early clinical days and is largely only used in humans today to treat rare diseases caused by specific mutations. While GLP-1 drugs are generally tolerable, it would take a considerable amount of work to confirm the safety and practicality of editing people’s cells to produce them. A lifelong therapy might also come with lifelong side effects, for example.
That said, it’s likely that some people would jump at the chance to take such treatments if they’re safe and reliable. And at least one pharmaceutical company is taking a shot at it. Fractyl Health has been developing its own GLP-1 gene therapy, which targets cells in the pancreas instead of the liver. In 2023, the company presented data showing that its gene-edited mice actually lost more weight than mice simply given semaglutide. This May, the company submitted paperwork to European health regulators for the first human trial of its gene therapy, which it expects to begin next year.
For now, semaglutide and other conventional GLP-1 drugs will remain atop the obesity treatment throne. In the not-so-distant future, though, who knows?
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