Following FDA approval of Foundayo (orforglipron), Novo Nordisk reports ORION data showing greater weight loss and better tolerability with oral semaglutide (Wegovy pill).
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Immediately following the U.S. FDA approval of Eli Lilly’s oral GLP-1 therapy orforglipron (marketed as Foundayo™), Novo Nordisk has released new data positioning its oral semaglutide 25 mg (Wegovy® tablet) as a potentially more effective option for weight management. The company announced results from the ORION study, an indirect treatment comparison suggesting greater weight loss and improved tolerability with semaglutide versus orforglipron.
The ORION study compared oral semaglutide 25 mg with orforglipron 36 mg using data from the Phase 3 OASIS 4 and ATTAIN-1 trials, respectively. Notably, the 36 mg dose of orforglipron used in trials corresponds to the FDA-approved Foundayo dose (17.2 mg tablet equivalent). As no direct head-to-head trials exist, Novo used a population-adjusted indirect comparison to generate these findings.
According to Novo Nordisk, oral semaglutide demonstrated significantly greater weight loss than orforglipron, with an estimated difference of about 3 percentage points across analytical models. These results were consistent regardless of whether treatment adherence scenarios or ideal conditions were considered, reinforcing the company’s claim of stronger efficacy.
Novo further reported that orforglipron was associated with higher discontinuation rates. The analysis showed approximately fourfold higher odds of stopping treatment due to any adverse event and nearly fourteenfold higher odds due to gastrointestinal side effects compared with semaglutide. However, the company acknowledged that these estimates are based on indirect comparisons and limited adverse event counts, which should be interpreted cautiously.
In parallel, Novo presented findings from the OPTIC patient preference study conducted in 800 adults with overweight or obesity. Based on modeled treatment profiles, 84% of participants preferred a semaglutide-like profile over an orforglipron-like option. Additionally, most respondents indicated that specific dosing requirements, such as taking medication on an empty stomach, would not significantly impact daily routines.
The timing of these data is notable, coming just after the regulatory entry of Foundayo into the U.S. market. While Novo’s analysis suggests potential advantages for oral semaglutide, the absence of direct comparative trials remains a key limitation. As no head-to-head trials exist, the ORION analysis is based on an indirect comparison, and cross-trial differences may limit interpretation of the findings.
Novo also reiterated the established safety profile of semaglutide, including a boxed warning for thyroid C-cell tumors and common gastrointestinal adverse effects such as nausea, vomiting, and diarrhea.
Novo Nordisk’s ORION and OPTIC findings, released in close proximity to Foundayo’s FDA approval, underscore intensifying competition in the oral obesity therapy space. While the company highlights favorable efficacy, tolerability, and patient preference for its Wegovy pill, further direct comparative evidence will be important to fully define the relative clinical value of these emerging oral treatments.
Reference
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, 02 April 2026, News Details
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.