Study Explores Gene Modifications for Diabetes Treatment

The rise in popularity of Ozempic and Wegovy, known for managing diabetes and aiding weight loss, has been remarkable. Many people contemplate how far they’d go to avoid one significant downside—the weekly injections. A recent study suggests that gene modifications could enable mice to produce their own Ozempic-like substances.

Researchers in Japan conducted the study, focusing on gene-editing techniques to alter the livers of mice, allowing them to internally produce exenatide, a first-generation GLP-1 drug. The modified mice maintained drug levels for several months and displayed more substantial health improvements than those who weren’t altered. Scientists speculate that similar methods could eventually lead to human applications, allowing people to create GLP-1s and other medications for a lifetime.

According to the authors, “This study suggests that genome editing could be used to create lasting treatments for complex diseases, potentially reducing the need for frequent medication,” as noted in their paper published Wednesday in Communications Medicine.

Semaglutide, the key ingredient in Ozempic and Wegovy, belongs to the class of GLP-1 drugs that have existed for about 20 years. These medications mimic the natural GLP-1 hormone, which plays a role in regulating appetite and insulin production. Semaglutide and similar drugs have proved to be significantly more effective for weight loss and blood sugar control than diet and exercise alone.

One reason for semaglutide’s superior effectiveness is that it’s designed to remain in the body longer, providing sustained effects lasting about a week. In contrast, the original formulation of exenatide required a daily or twice-daily dose, though there was a weekly version eventually replaced in the U.S. Many people find managing a weekly injection challenging, contributing to why some discontinue using semaglutide, alongside factors like high costs and side effects such as gastrointestinal issues.

Pharmaceutical companies are currently developing longer-lasting versions of GLP-1 drugs. Meanwhile, the team from Osaka University is exploring an alternative strategy. They posit that safely prompting our cells to produce specific drugs, such as GLP-1s, could entirely eliminate the need for ongoing dosing.

During the study, researchers initially placed the mice on high-calorie diets that led to obesity and prediabetes. Utilizing a CRISPR method, they inserted a gene into the liver cells of these mice, instructing them to produce exenatide. The treated mice maintained detectable levels of exenatide in their bloodstream for up to 28 weeks. Compared to untreated mice on the same diet, they consumed less, gained less weight, and exhibited improved insulin sensitivity, all without any evident side effects affecting their natural GLP-1 production.

Keiichiro Suzuki, a senior study author, expressed hope that their genetic treatment design could apply to various conditions lacking specific genetic causes.

However, it’s essential to note that these findings are currently a proof of concept. Gene therapy has not yet fully transitioned to practical use in humans, often being limited to rare disorders caused by specific mutations. While GLP-1 drugs are generally well-tolerated, ensuring the safety and practicality of editing human cells for such treatments presents significant challenges. Furthermore, a lifetime therapy could potentially lead to lifelong side effects.

That said, many individuals might eagerly embrace such treatments, provided they prove safe and effective. Notably, Fractyl Health is developing its own GLP-1 gene therapy, targeting pancreatic cells instead of liver cells. In 2023, the company reported findings showing that its gene-edited mice lost even more weight than those receiving semaglutide. They are preparing for a human trial submission next year.

For the time being, semaglutide and other conventional GLP-1 medications will continue to dominate obesity treatment. Yet, as advancements progress, who knows what the future might hold?