Ozempic Without the Nausea or Vomiting? This Drug Might Help

What if you could take Ozempic or similar GLP-1 drugs without having to worry about their gut-churning side effects? An experimental treatment being developed by the company Neurogastrx just might offer that sought-after possibility.

On Friday, the company released the latest data from its Phase II trial of their oral drug NG101. Volunteers who took NG101 while also on semaglutide (the active ingredient of Ozempic and Wegovy) experienced many fewer bouts of nausea and vomiting, the trial showed. The findings suggest that NG101 can help keep people from losing their appetite for taking GLP-1s for obesity.

“GI side effects are the leading reason why people discontinue GLP-1 treatment within the first year,†Jim O’Mara, Neurogastrx CEO, told Gizmodo.

An effective but nauseating drug

Semaglutide and similar agents work by mimicking GLP-1, a hormone that plays a key role in regulating our metabolism and hunger. The newest iterations of GLP-1 drugs have changed the landscape of obesity treatment in recent years, allowing people to lose much more weight on average than they would via lifestyle changes alone. But Ozempic isn’t a free lunch (see what I did there?).

People taking GLP-1s frequently report gastrointestinal symptoms like nausea and vomiting, especially as they increase their dosage of the treatment. Though these symptoms can wane over time, many people are unable to tolerate them and eventually stop using the drug. A recent study of real-world patients found that roughly two-thirds of people taking a GLP-1 for obesity discontinued therapy within a year, with many citing their GI symptoms as a contributing factor.

NG101 aims to prevent these complications by inhibiting one of the ways that GLP-1s can affect the brain. Research has suggested that GLP-induced vomiting is linked to the activation of the area postrema (AP), a structure found in the brainstem. Importantly, this activation of the AP doesn’t cause the appetite-reducing effects of GLP-1s, which are tied to a different region of the brain.

The AP is stocked with dopamine D2 receptors, and NG101 blocks the activity of these D₂ receptors. The structure also resides outside of the brain-blood barrier, whereas the other region affected by GLP-1s lies within it. Most drugs, NG101 included, can’t easily reach parts of the brain protected by the barrier. So by pairing NG101 with semaglutide, the idea is you can prevent vomiting caused by the latter without ruining its helpful benefits elsewhere.

Having your cake without puking it up

In this latest trial, 90 participants between the ages of 18 and 55 were given a single subcutaneous dose of semaglutide (0.5 milligrams). They also received either five days of NG101 (20 milligrams) or a placebo twice daily.

Compared to the placebo group, those on NG101 experienced a 40% reduction in nausea and a 67% reduction in vomiting, with a 56% reduction in the total episodes of vomiting. And even when people on NG101 did have nausea/vomiting, the symptoms lasted for a shorter time and were easier to handle. The severity of people’s nausea declined by 70%, for instance, based on the volunteers’ responses. The NG101 plus semaglutide combination group also experienced fewer adverse effects in general, indicating its potentially improved safety profile over traditional semaglutide.

“These study results are important because nausea and vomiting associated with GLP-1s prevent millions of patients globally from fully realizing the benefits of this transformative class of medicines,†O’Mara said.

The new data is being presented over the weekend at ObesityWeek, the annual conference of The Obesity Society. That means this study is still preliminary, since it hasn’t yet gone through the peer review process. And Neurogastrx is hardly the only one looking to make weight loss treatment less nauseating.

Some companies and research teams are studying whether it’s possible to create GLP-1 drugs that selectively avoid targeting the AP, for instance, while others are hoping to develop alternatives to GLP-1s that can provide similar effectiveness without the GI symptoms. But Neurogastrx is banking that its particular strategy can pay off sooner rather than later and that these latest results will fuel further interest from others in developing NG101 for regulatory approval.

“We are confident that NG101 offers a potential solution to a significant problem for people who want to use GLP-1s but can’t,†O’Mara said. “We’re looking forward to the data being presented and to having discussions with potential investors and partners about a path forward.â€

Judging from the emails I get as well as the accounts I hear from friends and others, there are certainly many people who’d be willing to try or stay on GLP-1s if they didn’t have to worry as much about the nausea and vomiting.