Dr Harith Rajagopalan looks at the booming market for weight-loss drugs like Wegovy and Ozempic and sees a multi-billion dollar bonfire. While millions have flocked to GLP-1 agonists to treat obesity and diabetes, studies show a sobering reality: most patients stop taking the injections within two years, erasing long-term cardiovascular benefits and wasting billions in healthcare spending. Also read | Endocrinologist explains dark side of weight loss drugs: Potential risks and benefits of Ozempic, Mounjaro, Wegovy
Dr Rajagopalan, a cardiologist and co-founder of the biotech firm Fractyl Health, believes the solution isn’t a better needle, but a fundamental rewrite of human biology. His company is preparing for human clinical trials of Rejuva, a gene therapy designed to program the body to produce its own GLP-1 hormone naturally for years following a single infusion. “We are literally lighting tens of billions of dollars on fire,” Dr Rajagopalan said of the current ‘forever drug’ model in a January 24 The Washington Post report.
A high-stakes clinical frontier
Fractyl’s approach reportedly involves a proprietary catheter that delivers a harmless virus directly into the pancreas. This virus instructs insulin-making cells to ramp up GLP-1 production. Because the hormone is produced locally, Fractyl suggests it may bypass the systemic ‘surges’ that cause the nausea and vomiting associated with current blockbuster drugs.
However, the permanence of gene therapy is its greatest risk. Unlike a daily pill or weekly shot, gene therapy cannot be easily ‘unplugged’. Giles Yeo, a professor at the University of Cambridge who studies the genetics of obesity, told The Washington Post of people who experience nausea and vomiting after taking GLP-1 medications: “The drugs, you can stop… if you genetically modify someone and they can’t stand it, they’re scr**ed.”
While Fractyl points to a ‘self-limiting mechanism’ in animal studies — where lean mice lost significantly less weight than obese mice— experts like Ohio State’s Lei Cao worry about the unknown. Specifically, the long-term effects of high GLP-1 levels in the pancreas, an organ not designed to be the primary factory for the hormone, remain a mystery.
The financial and competitive landscape
Fractyl is a ‘David’ in a land of ‘Goliaths’. While industry titans Novo Nordisk and Eli Lilly develop next-gen pills and even more potent shots, Fractyl is reportedly navigating ‘substantial doubt’ regarding its ability to continue as a going concern, according to recent regulatory filings.
The company reportedly ended 2025 with enough cash to fund operations through 2026, putting immense pressure on the upcoming clinical trials for Type 2 diabetes patients. Meanwhile, Wall Street has shown a preference for ‘gene-lite’ approaches as Wave Life Sciences stock reportedly surged 150 percent in late 2024 after an injectable drug (lasting six months) showed a 9 percent reduction in visceral fat. Additionally, Arrowhead Pharmaceuticals reported similar results from its own drug targeting the same gene, INHBE, by suppressing a protein that encourages the body to store energy rather than burn it.
A ‘cure’ for the coverage crisis?
For many patients, the interest in a one-time fix is driven by the ‘insurance cliff’. Dr Fatima Cody Stanford of Massachusetts General Hospital told The Washington Post that nearly 70 percent of her patients lost coverage for GLP-1 drugs this year as insurers balked at the high costs.
“The patients are coming off not because they want to, but because they have to,” she said. While she viewed a long-lasting therapy as a potential ‘cure’, she admitted the concept sounded almost ‘too good to be true’: “Would that really happen? This sounds almost like a cure, and we’ve never seen that to date.”
Fractyl argued that while the upfront cost of gene therapy is high (often ranging from high six figures to millions), it replaces the ‘indefinite pharmacy spend’ and provides more predictable health outcomes. As Fractyl prepares to seek regulatory clearance for a secondary procedure to regrow healthy gut tissue and begins its Rejuva trials, the medical community remains cautiously optimistic. If successful, Dr Rajagopalan won’t just have disrupted a market — he’ll have doused the fire of a failing pharmaceutical model.
Note to readers: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.
