Ozempic, But Without the Side Effects: Scientists Identify Plant Extracts with GLP-1 Agonist Potential

Scientists in Spain have discovered two plant extracts that have potential as GLP-1 agonist weight loss pills akin to semaglutide injections like Ozempic and Wegovy, following an AI-led study.

In May, the European Congress on Obesity will hear the results of an AI-led study carried out by scientists, who have identified two plant compounds that could be potentially used as GLP-1 agonist weight-loss pills.

The two compounds are derived from very common plants whose extracts have been associated with metabolic benefits. Their identity is being kept under wraps until patents are granted, and they’re currently undergoing a lab testing phase.

GLP-1 agonists like semaglutide have been proven to be effective in helping people lose weight. They replicate the action of a hormone called GLP-1, binding to and activating the hormone’s receptor in cells, which in turn reduces appetite, slows the release of food from the stomach, and prolongs the feeling of being full.

Semaglutide drugs like Ozempic, Wegovy and Mounjaro have taken over the consumer health and food industries in the last couple of years. While such drugs began life as treatments for type 2 diabetes, once the US FDA approved Wegovy for weight loss, sales ballooned and supplies strained, leading to many providers upping their Ozempic stock. In 2022 alone, nine million Americans were prescribed Ozempic, and that could rise to 24 million in the next decade, according to analysis by Morgan Stanley.

However, these drugs are associated with a wide array of side effects, and some say alternatives are needed. Elena Murcia from the BIO-HPC & Eating Disorders Research Unit at the Catholic University of Murcia in Spain is one of them. “Although the effectiveness of current GLP-1 agonists has been demonstrated, there are some side-effects associated with their use – gastrointestinal issues such as nausea, vomiting, and mental health changes like anxiety and irritability,” she notes. “Recent data has also confirmed that when patients stop treatment they regain lost weight.”

Using AI to identify Ozempic-like plant extracts

Murcia and her colleagues used high-performance AI techniques to identify non-peptide natural compounds that can activate the GLP-1 receptor. The team sifted through more than 10,000 compounds via virtual screening to find out which ones bind to the receptor.

More AI-based research explored how closely these bonds resemble the ones that occur between the GLP-1 hormone and its receptor, choosing the 100 most similar ones for further visual analysis. This was done to determine whether they interacted with key residues – amino acids – on the receptor. Then, they created a Venn diagram to identify the compounds with the highest potential as GLP-1 receptor agonists.

A total of 65 compounds were shortlisted, with two binding strongly to key residues. Titled Compound A and Compound B, the scientists are hoping that both can eventually be delivered in pill forms.

“Computer-based studies such as ours have key advantages, such as reductions in costs and time, rapid analysis of large data sets, flexibility in experimental design and the ability to identify and mitigate any ethical and safety risks before conducting experiments in the laboratory,” said Murcia.

“These simulations also allow us to take advantage of AI resources to analyse complex problems and so provide a valuable initial perspective in the search for new drugs.”

Shaking up the Ozempic-influenced food industry

Murcia explained that most GLP-1 agonists are peptides – which are short chains of amino acids that can be degraded by stomach enzymes, and at present, more likely to be injected rather than taken orally.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections. Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron,” she said. “These are synthetic and we were interested in finding natural alternatives.”

This will speak to a key consumer need. A 388-person survey by VC firm Coefficient Capital and tech outlet The New Consumer earlier this year revealed that while 72% of Americans would use GLP-1 drugs for weight loss if there were no side effects, this falls to 52% if there are side effects. Similarly, without these outcomes, 40% plan to start and stop based on needs, compared to 22% with no side effects.

But drugs like Ozempic and Wegovy are already leaving a huge mark on the food industry. People are buying fewer items in supermarkets, they’re eating less fewer carbs and less fat, drinking less coffee and sugar, and ditching fast food. Meanwhile, startups championing prebiotic fibre and gut health stand to gain from this shift, and giants like Nestlé, Danone and Unilever all pivoting their offerings to cater to the Ozempic era.

“We focused on plant extracts and other natural compounds because they may have fewer side effects,” said Murcia. Plants are also naturally rich in dietary fibre, which regulates the incretin hormone in our bodies that can boost GLP-1. Provided that her team’s research can break through in clinical trials, it could prove to be yet another shake-up in the interconnected food and health space. “If our AI-based calculations confirmed in vitro and then in clinical trials, we will have other therapeutic options to manage obesity.”