Gene therapy for weight loss: Can one shot replace lifelong GLP-1 drugs?

US biotech firm Fractyl Health is developing Rejuva, an experimental gene therapy that aims to trigger long-term weight loss by programming the pancreas to produce more GLP-1 hormone

What if the weight-loss drug that people have to inject every week could be replaced by a single treatment that works for years?

 

A new experimental gene therapy is aiming to change how obesity and diabetes are treated, moving beyond the need for lifelong use of glucagon-like peptide-1 (GLP-1) drugs, reported The Washington Post. GLP-1 is a hormone that regulates appetite and blood sugar. In a recent regulatory filing, US biotech company Fractyl Health said it is advancing Rejuva, an experimental therapy designed to help the body produce more of the GLP-1 hormone through a single procedure.

 

The filing draws on early animal studies published in a peer-reviewed journal, which showed significant weight loss after one dose. If the approach succeeds in humans, it could offer longer-lasting metabolic benefits and reduce the high drop-out rates seen with current GLP-1 medications, while also raising important questions around safety, cost and long-term effects, as you cannot easily “switch off” it.

 

 

What problem with GLP-1 drugs is this gene therapy trying to solve?

 

GLP-1 medicines have transformed diabetes and obesity care, but multiple studies show most patients stop these injections within one to two years, often due to side effects, cost or loss of insurance coverage. When people discontinue, many of the long-term benefits, including protection against heart disease, fade away.

 

Fractyl’s co-founder and chief executive, cardiologist Harith Rajagopalan, argues this stop-start reality wastes enormous resources and leaves patients short-changed. The company’s bet is that a long-acting biological solution could deliver steadier benefits without the need for constant dosing.

 

What is Rejuva and how does it work?

 

Rejuva is an experimental gene therapy delivered directly into the pancreas using a specialised catheter. It uses a harmless viral vector to instruct insulin-producing cells to make more GLP-1 hormone on their own.

 

Unlike injected GLP-1 drugs, which cause hormone levels in the blood to spike, Fractyl says its approach leads to more even, physiological GLP-1 signalling throughout the body. In theory, that could translate into fewer side effects such as nausea and vomiting.

 

What do the animal studies show so far?

 

In mice fed a high-fat diet, a single dose of Rejuva led to weight loss of up to 29 per cent within 35 days, according to data the company disclosed last year. In lean mice, weight loss was far more modest, around 6 per cent over three weeks, and did not trigger dangerously low blood sugar.

 

Fractyl describes this as a potential “self-limiting” effect, suggesting the therapy may have less impact when there is less excess weight to lose. While these results are eye-catching, experts caution that animal success often fails to translate cleanly into humans.

 

Why are some scientists uneasy about gene therapy for obesity?

 

According to The Washington Post report, some scientists are worried because with injectable drugs, unpleasant side effects can be managed by lowering the dose or stopping treatment, but gene therapy removes that safety valve. Thus, if the body produces too much GLP-1, reversing the effect could be difficult.

 

Some researchers also worry about the long-term consequences of producing high levels of GLP-1 inside the pancreas, an organ where the hormone is not normally made in large quantities. Potential cancer risks remain theoretical, but they underscore how little is known about chronic, local exposure over many years.

 

Fractyl points to evidence that current GLP-1 drugs are not linked to higher pancreatic cancer risk and may even be protective. Still, human data for a permanent or semi-permanent genetic approach do not yet exist.

 

Is there any way to control the therapy if something goes wrong?

 

There is no precise formula for dosing gene therapies, and companies often start at the lowest level expected to have an effect. Fractyl says it is doing exactly that as it prepares for human trials.

 

Some scientists note that drugs which counteract GLP-1 activity are in development and could, in principle, act as an external safety mechanism if hormone levels become too high. Fractyl stresses it is not relying on such an “antidote”, but acknowledges that future approvals could add another layer of reassurance.

 

When will human trials begin and who will be studied first?

 

According to the exchange filing, Fractyl plans to begin its first human clinical trial later this year. The initial study will enrol patients with Type 2 diabetes who have previously taken GLP-1 drugs without serious side effects but still struggle with high blood sugar.

 

A second version of the gene therapy, designed to stimulate both GLP-1 and another gut hormone, is being developed specifically for obesity.

 

What about cost and insurance coverage?

 

Cost remains a major concern. Approved gene therapies today often carry price tags from the high six figures to millions of dollars. Fractyl has not disclosed a potential price but says using smaller doses could lower manufacturing costs.

 

Health insurers have already pulled back on covering GLP-1 drugs, leaving many patients to stop treatment against their will. Whether payers would accept an even higher upfront cost for a one-time therapy, even if it promises long-term savings, remains an open question.

 

Despite the risks, interest is strong. According to Fractyl, many patients are eager for an option that does not depend on lifelong injections or uncertain insurance coverage. Fractyl says it receives daily enquiries from people wanting to enrol in future trials.

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