Oral GLP-1 Drugs Advance as Pharmaceutical Companies Race Toward Pill-Based Weight Loss Treatments
Multiple pharmaceutical companies are developing oral versions of GLP-1 receptor agonists. This class of drugs has changed the treatment landscape for obesity and type 2 diabetes. This month, two companies released Phase II trial data on competing oral candidates. Notably, Astrazeneca and Structure Therapeutics each reported weight loss results that are comparable to existing injectable therapies.
Both companies are now moving toward Phase III trials. The Food and Drug Administration requires this stage to support regulatory submission. GLP-1 receptor agonists mimic a naturally occurring peptide hormone that controls appetite and food intake. Semaglutide is a key example of this mechanism and has driven much of the recent growth in weight management treatments.
Most GLP-1 therapies need weekly subcutaneous injections because peptide molecules break down quickly in stomach acid. Therefore, manufacturers are looking for alternative formulations that allow oral use without losing effectiveness. Researchers have tackled this absorption issue with two different strategies. For example, the oral Wegovy tablet includes an absorption enhancer that protects semaglutide from being broken down in the stomach.
Separately, companies have created small molecule GLP-1 mimics that can withstand digestion without needing a protective additive. Eli Lilly’s filofiegrin is an example of this strategy. Astrazeneca’s once-daily small molecule candidate, elecoglipron, resulted in body weight reduction of up to 11.8 percent over 36 weeks. Specifically, two randomized, placebo-controlled Phase II trials produced these results.
Both studies were published in the Lancet. Meanwhile, Structure Therapeutics reported similar results for its candidate, aleniglipron. Patients lost up to 12.1 percent of body weight over the same time frame in that trial. These findings were published in Nature Medicine this month.
Researchers saw no new safety concerns during the aleniglipron trial. Investigators identified an effective dose and plan to slow dose increases in Phase III testing. This change improves how well patients tolerate the treatment. Additionally, this approach is a common way to manage gastrointestinal side effects related to GLP-1 therapy.
Several other oral candidates are still in earlier development stages. Roche’s CT-996, Ascletis’ ASC30, and Viking Therapeutics’ VK2735 are all going through clinical trials. Manufacturers are developing VK2735 in both injectable and oral forms. It’s unclear when any of these candidates will gain regulatory approval.
Each new candidate will compete against established companies like Eli Lilly and Novo Nordisk. Eli Lilly’s injectable retatrutide has shown weight loss results exceeding 30 percent in trials. This outcome highlights the competitive pressure facing oral treatments. As a result, increased competition within the GLP-1 drug class usually leads to lower prices.
Patient preference for oral options is already reflected in the market. This trend began after the launch of oral Wegovy this year. As more candidates enter Phase III trials, prescribing doctors and regulators will assess their efficacy. Officials will also keep an eye on safety and accessibility.
Ongoing action against counterfeit and compounded GLP-1 products will likely remain a priority for the FDA. Patient demand for these therapies continues to grow. Therefore, all GLP-1 medications discussed are only available by prescription under a doctor’s supervision.
