Plants May Hold Key to New Weight Loss Pills

AI finds two plant extracts that mimic GLP1 agonists like semaglutide and tirzepatide

Researchers have uncovered two promising plant compounds that could lead to a new class of weight loss drugs. The compounds were identified through advanced computer simulations as potential alternatives to medications like Ozempic and Mounjaro that mimic a key hunger-regulating hormone.

The search for plant-derived weight loss pills is driven by the limitations of current injectable GLP-1 agonist drugs according to Elena Murcia from the Catholic University of Murcia in Spain, who will present the findings at the European Congress on Obesity.

“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,” Murcia explained. “Recent data has also confirmed that when patients stop treatment they regain lost weight.”

GLP-1 (glucagon-like peptide-1) agonists like semaglutide (Ozempic) and tirzepatide (Mounjaro) work by mimicking the actions of the GLP-1 hormone to reduce appetite, slow stomach emptying, and increase feelings of fullness after eating. However, since they are composed of amino acid chains, they require injection to avoid being broken down by stomach enzymes before reaching the bloodstream.

“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,” said Murcia. While two promising non-peptide GLP-1 agonist compounds have been synthetically developed, Murcia’s team sought natural alternatives that may carry an even better side effect profile.

Using high-powered artificial intelligence and virtual screening techniques, the researchers analyzed over 10,000 plant compounds to identify those most likely to activate the GLP-1 receptor in a similar manner to the human GLP-1 hormone itself. This computational analysis whittled the field down to just two promising compounds.

“Compound A and Compound B bound strongly to the key residues [amino acid hotspots] on the GLP-1 receptor in a similar way to the leading synthetic compounds,” Murcia reported. “The two compounds are derived from very common plants, extracts of which have been associated with beneficial effects on the human metabolism in the past.”

While Murcia is keeping the plant sources and precise chemical identities of Compounds A and B confidential until patents are secured, she confirmed both have now advanced to laboratory testing to validate the computer modeling predictions.

“If our AI-based calculations are confirmed in vitro [in laboratory studies] and then in clinical trials, we will have other therapeutic options to manage obesity,” Murcia stated. “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.”

Should Compounds A and B ultimately prove successful and safe, Murcia envisions them as orally-administered, plant-derived weight loss pills with a potentially better side effect profile than current injectable GLP-1 drugs. But she cautioned that extensive further research lies ahead: “We are in the early stages of developing new GLP-1 agonists derived from natural sources.”