Oral GLP-1 weight‑loss pill shows 13% average loss in Phase 3, could reach market by 2026

A daily 25-milligram semaglutide pill produced meaningful weight loss in a Phase 3 trial, a development that researchers and clinicians described as potentially transformative for GLP-1 therapies and for needle-averse patients seeking obesity management.

In the randomized study conducted across four countries, overweight or obese adults were given either the semaglutide tablet plus diet and exercise counseling or a placebo plus the same counseling. Among 205 participants who received the pill, average body-weight reduction was 13.6% over 64 weeks, compared with 2.2% among 102 placebo participants. The trial’s authors noted that the oral form sought to address barriers associated with injections, including needle fear and refrigeration requirements, while maintaining the drug’s appetite-suppressing mechanism.

Novo Nordisk, which developed semaglutide, published the findings in The New England Journal of Medicine. The company is seeking U.S. regulatory approval to use the pill for obesity, with a decision expected from the Food and Drug Administration by the end of the year. If approved, the pill could reach the market in 2026. This could ease access and distribution, as an oral tablet is generally easier to produce at scale and less dependent on cold-chain logistics than injections.

The oral form could address barriers that have limited uptake of injectable semaglutide. Doctors and health-system officials have pointed to needle anxiety and the need for refrigeration as impediments to widespread use, particularly in settings with limited cold-chain infrastructure. An oral tablet could simplify prescribing and distribution and may help mitigate past supply-chain challenges seen with injectable GLP-1 therapies.

Side effects were common and similar in nature to those seen with injectable semaglutide. About 74% of participants on the pill experienced gastrointestinal issues, such as nausea or dyspepsia, compared with 42.2% in the placebo group. Castro-Tié noted that these side effects align with the drug’s mechanism and that, with the oral formulation, symptoms may emerge more slowly and persist longer than after injections. He added that the overall GI profile is consistent with what has been observed with the injectable form, though the onset and duration can differ by route of administration.

Beyond this study, several GLP-1–based pills are in development. Novo Nordisk already has Rybelsus, an oral semaglutide approved for adults with Type 2 diabetes, and Eli Lilly’s orforglipron, another GLP-1–mimicking drug, has completed late-stage trials and is nearing market for obesity and Type 2 diabetes management.

As regulators weigh the data, health experts say an approved oral semaglutide could broaden access to a proven class of medications that address obesity and metabolic disease. If the FDA clears the pill by year’s end, manufacturers have signaled readiness to ramp up production for a potential 2026 rollout, subject to pricing decisions and payer coverage. The broader GLP-1 landscape remains competitive, with ongoing trials and potential new entrants aiming to replicate or improve upon the weight-loss and glycemic benefits observed in this Phase 3 program.