Nove regained his weight loss leg in the doll arena – but Lily is coming

After losing significant ground to rival Eli Lilly in the GLP-1 space over the past two years, Novo Nordisk is defending the field it now dominates — oral therapies. But as Lilly prepares to launch an obesity pill, or forgliperone, as early as the second quarter, can Novo’s grip on the oral market last?

This year has been a rocky start for the Danish pharma giant. The company said last month that it expects sales and profits to decline in 2026 as it faces federal pricing restrictions, and stiff competition from Lilly and Compounding Pharma.

The company’s shares have fallen after a series of disappointing clinical readings, wiping out nearly all of the stock’s gains since its blockbuster obesity shot Vigovi was approved nearly five years ago.

Faced with pressure on multiple fronts, Novo is doubling down on next-generation oral peptides with improved tolerability while forging new partnerships to strengthen its pipeline. But Lilly is now trespassing in the healing space as well.

A new track record with bullets

Novo became the first oral pioneer with the GLP-1 pill, Rybelsus, which was approved by the FDA in 2019 for type 2 diabetes. The pharma giant reached another milestone late last year when the agency OK’d Vigovi’s oral formulation, the first oral GLP-1 approved for weight loss.

Since its launch in the United States in early January, sales of Vigovi pills have soared. The drugmaker said more than 600,000 prescriptions were written in the first two months alone, many of which went to patients new to the GLP-1 drug.

Meanwhile, Novo has ended up losing several head-to-head tests against its main rival in the ongoing battle for the best injectable options.

The company recently reported that its next-generation obesity shot CagriSema failed to top Lilly’s dual GLP-1/GIP agonist Zepbound in a head-to-head comparison study.

A fixed-dose combination of Novo’s best-selling drug semaglutide and the amylin analog coagrelintide was initially championed as a candidate that could overtake Lille Monjaro and return Novo to market leadership. But when Kaigre Sima fell short of Zip Bound’s 25% weight loss benchmark, those hopes were dashed.

A few days later, Lily reported another victory, this time for diabetes. The company’s GLP-1 pill orforglipron did better than the new Rebelsos in the first phase of its kind, leading to more weight loss and lower blood sugar levels. However, these benefits from the pill, which is currently under FDA review, have come at the cost of high side effects.

Patients taking orforglipron were actually more likely to discontinue treatment due to side effects than those taking Rybelsus. Discontinuations due to adverse events were approximately doubled in the orforgliprone groups, regardless of dose.

A new oral tender

With tolerability becoming a key competitive differentiator in the GLP-1 field, Novo is focused on improving its oral drug delivery — the most difficult task in obesity and diabetes treatment development. To get there, start making new deals.

A day before Rybelsus trial results came down, Novo announced it had signed a $2.1 billion deal with biotech startup Vivtex Corp. to develop new oral biologics for obesity, diabetes and other metabolic diseases. The partnership combines nine decades of experience in protein and oral peptide engineering with Vivtex’s proprietary drug screening technology to identify oral assets with improved bioavailability and tolerability.

Their collaboration aims to overcome the challenges of developing oral biologics, which are generally poorly absorbed in the GI tract. If Novo can develop a biologic that’s easier to take while maintaining strong efficacy, big pharma could regain some market ground. But with a wave of new candidates making their way through the clinic, Novo’s position in the oral GLP-1 market is likely to remain turbulent.