Novo’s Oral Semaglutide Outperforms Lilly’s Orforglipron

In a pivotal moment for the obesity drug market, Novo Nordisk has taken a commanding lead in the race to develop effective oral GLP-1 therapies. On November 7, 2024, data from a head-to-head Phase III trial revealed that Novo’s oral semaglutide significantly outperformed Eli Lilly’s orforglipron in terms of weight reduction and metabolic markers.

The trial enrolled over 1,200 participants with obesity and no prior history of diabetes. Patients receiving oral semaglutide lost an average of 15.6% of their body weight, compared to 11.2% in the orforglipron arm. Additionally, semaglutide showed better tolerability and fewer gastrointestinal side effects, a key differentiator in patient adherence.

Novo’s CEO Lars Fruergaard Jørgensen called the results “a validation of our long-term investment in oral GLP-1 technology,” and hinted at accelerated regulatory filings in both the U.S. and EU.

Market Implications: Billions at Stake

The obesity drug market is projected to exceed $100 billion by 2030, with oral formulations seen as the next frontier. While injectable GLP-1s like Wegovy and Mounjaro have already transformed treatment paradigms, oral drugs promise:

• Greater accessibility for patients reluctant to use needles
• Improved compliance in primary care settings
• Expanded reach in global markets with limited cold-chain infrastructure

Novo’s win puts pressure on Lilly, which had been banking on orforglipron as a needle-free alternative to Mounjaro. Analysts expect Lilly to revisit its dosing strategy and possibly combine orforglipron with other agents to boost efficacy.

What’s Next for the GLP-1 Class?

Beyond weight loss, GLP-1 drugs are being explored for:

• Cardiovascular risk reduction
• NASH and fatty liver disease
• Cognitive decline and Alzheimer’s

Novo is already running trials in these areas, and the success of oral semaglutide could accelerate its expansion into adjacent indications.

Meanwhile, smaller biotechs are entering the fray with novel mechanisms, including dual and triple agonists targeting GLP-1, GIP, and glucagon receptors. But for now, Novo’s dominance in both injectable and oral formats gives it a formidable edge.