New Data Ranks Oral Obesity Drugs on Weight Loss Performance

Two new studies comparing oral Wegovy 25 mg (semaglutide) and Foundayo (orforglipron) indirectly compare the two in effectiveness.1 The data, being presented at the Obesity Medicine Association's annual conference in San Diego, arrive shortly after the FDA approved orforglipron, giving the market its second oral GLP-1 option.

The comparison was indirect, drawing on data from two separate phase III trials, OASIS 4 for oral semaglutide and ATTAIN-1 for orforglipron, rather than a head-to-head study.1 Analysts and developers should note that limitation, though the methodology adjusted for key baseline differences, including body weight, glycemic status, and sex. Residual differences between trial populations and protocol designs may still influence comparability.

On weight loss efficacy, oral semaglutide 25 mg outperformed orforglipron 36 mg by a mean of 3.2 percentage points regardless of whether patients stayed on treatment, and by 3 percentage points in a scenario modeling full adherence.1 Both differences carried 95% confidence intervals that excluded zero, suggesting the gap is unlikely to be attributable to chance alone.

The tolerability findings may carry equal or greater weight for those thinking about long-term commercial viability of these molecules.1 Patients taking orforglipron 36 mg were approximately 4 times more likely to stop treatment due to any adverse event compared to those on oral semaglutide 25 mg, and roughly 14 times more likely to discontinue specifically due to gastrointestinal side effects. The authors caution that the absolute numbers of adverse events were low, so the ratios should be interpreted carefully.

Jamey Millar, executive vice president of US Operations, Novo Nordisk, noted, in a press release,1 "These studies add to the growing body of evidence supporting the clinical strength of semaglutide and highlight attributes that patients value when choosing an obesity medicine that fits their lifestyle."

Robert Kushner, MD, Northwestern Feinberg School of Medicine, stated in the press release,1 "People often ask how one medication compares to another when making obesity treatment management decisions. Since there are no head-to-head trials comparing oral semaglutide for obesity to orforglipron, this indirect treatment comparison from the ORION study provides important information that can be used during the shared decision-making process."

How Are Patients Likely to Factor Into Market Uptake?

A parallel patient preference survey conducted among 800 US adults with obesity or overweight adds a demand-side dimension that matters for anyone forecasting volume or modeling commercial trajectories for either molecule.1 Run between October and November 2025, the survey presented respondents with hypothetical treatment profiles modeled on the two drugs' clinical characteristics: efficacy, cardiovascular risk reduction, dosing instructions, and administration requirements, among other attributes.

Eighty-four percent of respondents preferred the profile resembling oral semaglutide 25 mg over the orforglipron-like alternative.1 One attribute that might have been expected to disadvantage semaglutide, its requirement to be taken on an empty stomach with a 30-minute wait before eating, was not widely seen as a barrier. Sixty-five percent of all respondents said that dosing requirement would not disrupt their daily lives.

This preference data carry practical implications.1 Patient adherence is a known driver of real-world efficacy, and persistent discontinuation due to gastrointestinal side effects has been a recurring challenge across the GLP-1 class. Tolerability differentiation between 2 oral agents in the same indication could meaningfully affect adherence rates at scale, with downstream consequences for outcomes data, lifecycle positioning, and payer negotiations.

It is worth noting that the survey was completed before orforglipron received regulatory approval, meaning the profiles presented to respondents may not precisely reflect FDA-approved labeling for either product.1

Oral semaglutide 25 mg carries a boxed warning for possible thyroid tumors, including cancer, and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. 1 Its most commonly reported side effects include nausea, diarrhea, vomiting, constipation, and abdominal pain, among others.

How Does Novo Nordisk's Pipeline Strength Extend Beyond Oral Obesity Drugs?

The oral semaglutide and orforglipron comparison data arrive at a moment when Novo Nordisk is demonstrating broader ambitions across metabolic disease.2 The FDA's approval of Awiqli (insulin icodec-abae), the first once-weekly basal insulin indicated for adults with type 2 diabetes, signals that the company's pipeline activity is not confined to the GLP-1 obesity market. Supported by the ONWARDS phase III program across approximately 2680 adults, Awiqli reduced daily basal insulin injections to one per week, with a safety profile consistent with the existing basal insulin class. A US launch is expected in the second half of 2026.

References

1. Novo Nordisk A/S. Awiqli approved in the US, the first and only once-weekly basal insulin treatment for adults with type 2 diabetes. March 26, 2026. Accessed April 2, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916526.
2. Novo Nordisk A/S. Awiqli approved in the US, the first and only once-weekly basal insulin treatment for adults with type 2 diabetes. March 6, 2026. Accessed April 2, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916521.