A new once-daily oral drug, orforglipron, is showing promising results in helping patients maintain weight loss after discontinuing injectable treatments such as Wegovy and Zepbound. The pill could offer a more convenient and accessible option for people with obesity who find long-term injections difficult.
Early findings from a large Phase 3 clinical trial suggest that orforglipron may help preserve weight loss achieved with earlier GLP-1 therapies. This approach could address one of the biggest challenges in obesity treatment: preventing weight regain after medication discontinuation.
Researchers say the results highlight the growing potential of oral GLP-1 therapies in long-term weight-loss management.
Obesity continues to rise as a major public health challenge, with a significant share of adults now living with overweight or obesity, placing long-term strain on healthcare systems and increasing the risk of chronic disease.
Although injectable weight-loss medicines have transformed obesity treatment and delivered meaningful results for many patients, they also create practical barriers, including frequent injections, regular clinic visits, and difficulties with long-term adherence.
In this context, an effective oral alternative could simplify treatment pathways, improve convenience, and widen access for people who dislike needles or struggle to maintain injectable therapy over time.
Eli Lilly and Company led a pivotal Phase 3 clinical trial known as ATTAIN‑MAINTAIN to test whether orforglipron can help people hold on to the weight they lost after injectable treatment.
The study enrolled adults with obesity or overweight who first completed another trial, SURMOUNT‑5, where they received high‑dose injectable GLP‑1 therapies (semaglutide or tirzepatide). Participants then switched to either orforglipron or a placebo for 52 weeks while following a healthy diet and physical activity regimen.
The study used a randomised, double‑blind, placebo‑controlled design , the gold standard in clinical research. Its main aim was to show that orforglipron preserved weight loss better than placebo over one year.
After 12 months on orforglipron, patients who transitioned from Wegovy largely maintained their weight loss, showing an average difference of just 0.9 kg from their weight at the start of the oral treatment phase.
Those moving from Zepbound maintained their weight with an average difference of 5.0 kg.
These outcomes were significantly better than placebo, which saw much higher weight regain in comparative analyses. In a 24-week follow-up analysis, patients who switched from Wegovy to orforglipron showed virtually no change in body weight, while those receiving placebo experienced noticeable weight regain.. Similarly, orforglipron recipients transitioning from Zepbound regained far less weight than their placebo peers.
In simple terms, orforglipron helped many people keep off most of the weight they had initially lost with injectable therapy , a major step forward in chronic weight management.
Orforglipron belongs to a class of drugs called GLP‑1 receptor agonists. These medications mimic a naturally occurring hormone that slows gastric emptying, helps regulate blood glucose, and increases satiety.
Unlike most GLP-1 therapies, orforglipron is a once-daily small-molecule oral tablet with no food or water restrictions, making it a potentially more practical alternative to injections.
This convenience could significantly improve adherence for many patients. Daily oral dosing may also broaden access to treatment, especially for those who are needle‑averse or who struggle with clinic‑based injections.
The trial found that orforglipron’s safety profile was consistent with other GLP‑1 receptor agonists. Most side effects were gastrointestinal (such as nausea and diarrhoea) and generally mild to moderate in severity. No liver safety issues were detected. Discontinuation rates due to adverse events were low across groups.
Regulatory reviews of orforglipron are ongoing, with decisions expected in early 2026. If approved by authorities such as the MHRA or the European Medicines Agency (EMA), the drug could be widely prescribed as a maintenance treatment for obesity. Oral dosing may also ease pressure on NHS services by offering a simpler alternative to injectable therapies.
However, experts note that injectable GLP‑1 drugs still deliver some of the greatest average weight loss seen in clinical practice. Even so, an oral pill with strong maintenance effects could fill an important gap for long‑term weight management strategies.
Industry analysts say these results bolster orforglipron’s case as a maintenance therapy and not merely a competitor to existing oral GLP‑1 drugs. Some also point out that regulatory momentum is building around oral obesity treatments, with other pills (like oral Wegovy) recently approved in the US.
Ultimately, orforglipron’s success will depend on regulatory approval, pricing, and how widely clinicians adopt it alongside lifestyle interventions and existing treatments. Its convenience could make it attractive to both patients and healthcare systems looking for long-term obesity solutions.
The ATTAIN‑MAINTAIN trial signals a potential shift in how weight management is approached after injectable GLP‑1 therapy. Orforglipron’s ability to help people keep weight off , with daily oral dosing and tolerable side effects , makes it a promising candidate in a crowded obesity drug market. Continued research and regulatory review will determine whether this pill becomes a mainstream option globally.
Sources:
- Eli Lilly and Company. (2025, December 18). Lilly’s orforglipron helped people maintain weight loss after switching from injectable incretins to oral GLP‑1 therapy in first‑of‑its‑kind Phase 3 trial. PR Newswire. (prnewswire.com)
- Reuters. (2025, December 18). Lilly pill helps maintain weight loss in trial after switch from injectables. Reuters. (Reuters)
