Early Responders With Oral Semaglutide Indicate Long-Term Weight Loss

New clinical data presented at the European Congress on Obesity provided a more nuanced understanding of the oral semaglutide 25 mg (Wegovy pill), demonstrating that early weight loss response serves as a strong predictor for long-term success. According to subanalyses of the phase 3 OASIS (NCT05564117) 4 trial, nearly 1 in 3 adults were classified as early responders, achieving an average weight loss of 13.2% within the first 4 months of treatment.¹

By the end of the 64-week trial, these early responders reached a total mean weight loss of 21.6%, while those who did not meet the early response criteria still achieved a clinically meaningful 11.5% weight loss. These findings provide pharmacists and other health care providers with a practical tool for managing patient expectations and dose escalation by monitoring the rapidity of weight loss following the initiation of treatment.

About the Data

The clinical benefits of oral semaglutide 25 mg extend beyond weight reduction, showing a profound impact on patient mobility and daily living. In a separate analysis of the OASIS 4 trial, researchers found that nearly 8 in 10 patients with poor physical function at baseline achieved clinically meaningful improvements in their ability to move, bend, and stay active.¹

Specifically, 77.3% of those in the semaglutide group saw improved function scores compared to just 42.9% in the placebo group. These results, which were consistent regardless of the total amount of weight lost, underscore the drug's potential to significantly enhance the quality of life for patients struggling with obesity-related physical limitations.^1,2

Comparative data from the ORION and OPTIC studies further distinguish oral semaglutide 25 mg from other emerging oral therapies, such as orforglipron. In an indirect treatment comparison, oral semaglutide 25 mg demonstrated significantly greater mean weight loss than orforglipron 36 mg.^1,3

Perhaps more critical for long-term adherence, the comparison showed that orforglipron was associated with approximately 14 times higher odds of treatment discontinuation due to gastrointestinal adverse effects (AEs). Patient preference data supported these findings, with 84% of survey respondents favoring a treatment profile similar to oral semaglutide over an orforglipron-like profile. Notably, 65% of patients indicated that the specific dosing requirements for oral semaglutide—taking the pill on an empty stomach and waiting 30 minutes before consuming food or other medications—would not disrupt their daily lives.^1,3

What Pharmacists Should Know

For pharmacists monitoring the holistic health of their patients, the cardiometabolic advantages of the 25 mg oral dose are particularly noteworthy. Post hoc analysis of the OASIS 4 trial revealed that treatment led to significant improvements in glycemic parameters, including reductions in hemoglobin A_1C, fasting plasma glucose, and fasting serum insulin levels. Furthermore, investigators observed positive changes in cardiovascular risk factors such as C-reactive protein and serum triglycerides. These improvements in metabolic health were evident across the study population, though they were most pronounced in patients who achieved greater than 15% weight loss. This data suggests that oral semaglutide 25 mg can be a valuable therapeutic option for managing the complex interplay between obesity and cardiovascular health.

Despite its high efficacy, pharmacists must remain diligent regarding the safety profile and administration of this medication. The most common AEs reported in the OASIS 4 trial were gastrointestinal in nature, occurring in 74% of participants taking the drug compared to 42.2% in the placebo group.^1,3

“Since we’re seeing so many drugs that are beneficial in different areas like obesity, heart disease, kidney disease, liver disease, that type of thing, we as health professionals—doctors, nurses, nutritionists, pharmacists—we need to look at the patient as a whole,” Staci-Marie Norman, PharmD, CDCES, FAPhA, a recently retired pharmacist and diabetes specialist at Martin’s Pharmacy in Indiana, said.⁴ “If I’m a cardiologist looking at the heart, if I’m a nephrologist looking at the kidney, endocrinologist at the diabetes, we need to be looking at the whole.”

Most of these effects were mild to moderate and typically diminished over time. Additionally, the medication carries a boxed warning for the risk of thyroid C-cell tumors, and it is contraindicated for patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. As the evidence base grows, including data from other trials like STEP UP (NCT05646706), which showed higher doses of semaglutide helping patients reach healthy cardiovascular targets, oral semaglutide 25 mg continues to solidify its role as a potent and preferred oral option in the chronic management of obesity.^1-3

“Making sure that we’re getting the right medicine for the right patient is really super important,” Norman said. “I think that there’s great benefits for the GLP-1s, and they’re wonderful for our arsenal of medications.”

READ MORE: Obesity Management Resource Center

Are you ready to elevate your pharmacy practice? Sign up today for our free Drug Topics newsletter and get the latest drug information, industry trends, and patient care tips straight to your inbox.

REFERENCES

1. Wegovy pill delivered 21.6% weight loss in early responders and doubled mobility improvement, according to new Novo Nordisk data at ECO2026. News release. Novo Nordisk. May 13, 2026. Accessed May 18, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916548

2. Gallagher A. Oral semaglutide shows improvements in blood glucose, cardiovascular risk factors. Drug Topics. November 8, 2025. Accessed May 18, 2026. https://www.drugtopics.com/view/oral-semaglutide-shows-improvements-in-blood-sugar-cardiovascular-risk-factors

3. Wegovy pill demonstrated greater weight loss than orforglipron and lower odds of stopping medication due to side effects in a new indirect comparison to be presented at Obesity Medicine Association 2026. News release. Novo Nordisk. April 2, 2026. Accessed May 18, 2026. https://www.prnewswire.com/news-releases/wegovy-pill-demonstrated-greater-weight-loss-than-orforglipron-and-lower-odds-of-stopping-medication-due-to-side-effects-in-a-new-indirect-comparison-to-be-presented-at-obesity-medicine-association-2026-302732768.html