Nuohe finally won the battle against Tilpotide, but the market didn't buy it.

On September 21st, Novo announced the latest data from two Phase III clinical studies of CagriSema on Capital Market Day. Both studies achieved the primary endpoint, and the safety was consistent with previous studies, with no new safety signals found.

What is more noteworthy is that in the "head to head" experiment with tilboptin, CagriSema showed a weight loss effect superior to tilboptin.

Specifically, in this trial called REIMAGINE 5, CagriSema reduced the average weight of patients with type 2 diabetes by 12.4%, and Lilly's Tilpolide by 9.1%. Another REDEFINE 9 study showed that in overweight or obese adults, CagriSema lost 21.0% weight, while the placebo group lost 2.0%.

CagriSema is positioned as the next-generation core weight loss drug of Novo Nordisk. But for this good news, the market did not buy it.

On September 21st, the stock price of Novo Nordisk remained sluggish, with a decline of nearly 8%. Novo has been in a difficult situation for too long and urgently needs a new story to boost confidence. Obviously, the surprises brought by CagriSema are not enough.

01. CagriSema won, why isn't the market buying into it

Tilpotide once caused a lot of trouble for Nuohe.

Eli Lilly has demonstrated through a "head to head" clinical trial that the weight loss effect of tilboptin is significantly better than that of semaglutide, and has since achieved a comeback to surpass Novo Nordisk. Citibank analysts pointed out that Eli Lilly has already occupied nearly 57% of the GLP-1 market share, while Novo Nordisk's share remains relatively stable at 37%.

In 2025, the annual sales revenue of Tilpotide will reach 36.507 billion US dollars, surpassing the 36.1 billion US dollars of the entire Simeglutide series, officially topping the "Global Medicine King".

In 2026, the sales gap between the two parties will continue to widen. In the first half of 2026, the sales revenue of Eli Lilly's entire range of Tilpotide products reached 27.693 billion US dollars, a year-on-year increase of 88%; The product portfolio of Novo Smirnotide, including hypoglycemic and weight loss indications, has a total sales revenue of 112.193 billion Danish kroner, equivalent to approximately 17.5 billion US dollars.

With the iterative development of the weight loss drug market, players including Eli Lilly and Novo have entered the competition for the next generation of drugs. CagriSema naturally became the most important card for Novo in the second half of the battle for weight loss drugs.

However, in February of this year, Novo Nordisk announced that CagriSema failed to demonstrate non inferiority compared to tilboptin in the REDEFINE 4 study.

This 84 week open label study included 809 obese patients with an average baseline weight of 114.2 kilograms. Among the patients who persisted in medication, the CagriSema (2.4mg/2.4mg) group lost 23.0% weight, while the Tilpotide (15mg) group lost 25.5% weight; According to the estimated value of the treatment plan, the two groups lost 20.2% and 23.6% weight respectively.

After the announcement, the stock price of Novo Nordisk fell by over 10% at one point.

Nowadays, with the update of new clinical data from CagriSema, the market is inevitably curious: why did the results of CagriSema's "head to head" tilboptin reverse in just a few months?

The answer is actually quite simple, because these two clinical trials target different populations.

REDEFINE 4 is compared to a high-dose CagriSema of 2.4mg/2.4mg on 15mg tilboptide. The subjects are obese and the main focus is on the non inferiority of weight loss.

REIMAGINE 5 was administered at a low dose of 1.0mg/1.0mg CagriSema to 5mg Telopotide in patients who had poor blood glucose control after treatment with metformin, SGLT2 inhibitors, or a combination of both.

As of week 60, CagriSema achieved an excellent weight loss effect, with an average weight loss of 12.4% for participants, compared to 9.1% in the tilboptide group; At the same time, CagriSema reduced glycated hemoglobin (HbA1c) by 1.71%, while the tilboptide group reduced it by 1.67%, achieving the non inferiority primary endpoint.
The dosage, population, and endpoint of the two experiments are different.

Martin Holst Lange, Executive Vice President and Chief Scientific Officer of Novo Nordisk, stated in his speech: "With a dose of only 1.0 mg/1.0 mg, the weight loss effect of CagriSema is superior to that of 5 mg of tilboptide. ”

The implication is that REIMAGINE 5 has chosen a low-dose design, leaving room for further dosing of Cagrisma - if higher doses are introduced in the future, the weight loss effect may still be improved.

CagriSema is a fixed dose combination formulation of semaglutide and the long-acting amygdalin receptor agonist Cagralintide, injected once a week. The latter further suppresses appetite and delays gastric emptying by activating the amygdalin receptor. This is also the difference between CagriSema and the dual target mechanism of GIP/GLP-1 in tilpotide.

GLP-1 plus amylin, this is the new story that Novo tells CagriSema. But obviously, the market did not buy it.

02. Novo needs the next semaglutide

REIMAGINE 5 has not completely dispelled the concerns brought by REDEFINE 4. Because the market anxiety is not about CagriSema, but whether CagriSema can help Novo sustain growth.

The biggest headache facing Nuohe is that the cash cow, semaglutide, has already entered the countdown.

Smeglutide has always been the core pillar of Novo diabetes and obesity business. In the first half of 2026, the adjusted total sales of Simeglutide amounted to 112.193 billion Danish kroner, accounting for 64% of the total sales.

Novo CEO Mike Doustdar bluntly stated that the expiration of Simeglutide's patent is like an 'elephant in the room'. This sentence is not exaggerated.

IQVIA's statistics show that semaglutide is experiencing a global wave of patent expiration. In 2026, the first batch of key markets, including Canada, Brazil, China, India, Mexico, Türkiye, Saudi Arabia, and South Africa, will enter the stage of patent and data protection expiration; Subsequently, it will also expand to the Baltic States and some regions of Central and Eastern Europe; Most importantly, the relevant patents in the United States are expected to expire in 2032.

The competition in the Chinese market has also started ahead of schedule. According to the Insight database, currently 10 generic drugs of semaglutide have been declared for market, and another 11 have entered phase III clinical trials.
According to the latest performance guidance, Novo Nordisk predicts that its sales and operating profit may decrease by 5% to 13% in 2026. This may be the first time since entering the GLP-1 era that Novo has faced an annual performance decline.

Since taking office, Doustdar has been making drastic reductions, including cleaning some pipelines, including some weight reducing pipelines.

In November 2024, Novo Nordisk reached a monthly GLP-1 drug TransCon Semaglutide cooperation agreement with Ascendis Pharma, with a potential total amount of $285 million. But in September of this year, this agreement was confirmed to be terminated and the authorized license will be returned to Ascendis.

Also abandoned is the oral CB1 receptor inverse agonist monlunabant, which was one of the core pipelines acquired by Novo Nordisk for $1.1 billion in 2023. At this point, all candidate drugs obtained during the acquisition of Inversago have been abandoned.

The pipeline is undergoing subtraction, and the organization is also undergoing subtraction.

Novo Nordisk disclosed on this capital market day that the organizational restructuring involves approximately 13000 positions, and this round of restructuring is expected to save more than 10 billion Danish kroner per year, approximately 1.535 billion US dollars. The saved funds will be reinvested in commercialization and research and development.

03. Weight loss remains the main focus of the future

According to Novo's sharing on Capital Market Day, weight loss will remain the company's core focus in the coming years.

According to data cited by Novo, the global adult obesity population is expected to increase from 942 million in 2025 to 1.23 billion in 2035, an increase of approximately 31%; However, the current penetration rate of obesity medication treatment is still less than 2%.

In Novo's view, this means that the market is far from reaching its ceiling.

More importantly, obesity is not simply a matter of weight. Obesity is associated with over 200 complications, making it not just a matter of weight, but a gateway to a range of chronic diseases.

The potential population is also very large - more than 550 million people with diabetes, more than 900 million people with obesity, more than 550 million people with cardiovascular diseases, more than 300 million people with liver diseases, and more than 13 million people with blood and endocrine diseases.

The plate is large enough, but problems also arise. The weight loss needs of different types of patients vary. Therefore, the next stage of Novo's approach is no longer to search for the next "stronger" drug, but to precisely meet the needs of different patients.

Novo Research shows that over 50% of people prefer oral treatment; 40% of people have one or more complications, 38% are concerned about gastrointestinal side effects, and 33% have discontinued medication due to side effects; 32% pursue the highest possible weight loss, 30% hope to see results as soon as possible, 29% are concerned about muscle loss, and 24% are concerned about drug interactions.

This list of requirements is actually a map of Novo's future product layout. Weight loss range, muscle preservation, tolerance, convenience, onset speed, price, complications - each demand may correspond to a new product route.
Therefore, Novo is continuing to expand its product matrix outward.

In the oral market, Novo currently holds a first mover advantage once again. According to the latest data from IQVIA, Wegovy is still far ahead in terms of prescription volume.

Regarding the oral route, Novo Nordisk did not solely rely on semaglutide. Novo presented three candidate oral weight loss drugs. Among them, oral ACSL5i is targeted at GLP-1 intolerant individuals and can be used as a combination option with other weight loss drugs; Oral zenagamtide is the first and best single molecule GLP-1 and amygdalin dual agonist in its class, and has entered phase III; The core selling point of oral amylin 355 is its better gastrointestinal tolerance.

In other words, what Novo wants to do is not an oral weight loss medication, but a complete set of oral product combinations.

At the same time, Novo is also supplementing multi-target assets.

In 2025, Novo Nordisk introduced the GLP-1/GIP/GCG triple target agonist UBT251 from Federal Pharmaceuticals. The drug's phase II study in China showed a maximum weight loss rate of 19.7% at 24 weeks. Novo Nordisk plans to retrieve phase 1b/2a data in the first half of 2027 and initiate phase III weight loss in mid-2027.

Behind this, it is actually Novo's judgment on the next stage of competition: in the future weight loss market, it will be difficult to satisfy all people with just one product. Whoever can provide more choices between different therapeutic effects, tolerability, prices, and administration methods is more likely to cover a larger patient population.

For this reason, Novo proposes to launch at least one potential blockbuster product in the field of obesity every year before 2030, and to compress the average period from the first human dose of obesity and diabetes peptides to the declaration to five years or less. This requires the company to accelerate its research and development speed.

In terms of research and development strategy, Novo will accelerate the development pipeline through various methods such as pipeline organization, end-to-end AI and data science, clinical and market insights feedback, external innovation, etc.

Novo has merged research and development into one organization and reorganized its R&D portfolio according to strategic priorities.

AI is also embedded in various stages of drug discovery and clinical development. AI can help improve target hit rates, shorten the design synthesis testing analysis cycle, and significantly reduce the time required for clinical report generation, trial site selection, and patient population analysis.

One of the cases is that Novo utilizes an active learning mode of "manual design+machine learning" to optimize the monthly production of amygdalin analogs. After multiple iterations, the time to reach the candidate is reduced by about 50%, and the DMTA cycle is reduced by about 60%.

The true value of AI here is not to make decisions for scientists, but to help R&D avoid some detours. This is particularly important for Novo because what it is facing now is essentially a race against time.

On the one hand, Novo invests about 50% of its research and development resources in new mechanisms and high-risk innovation, in search of the next generation of growth engines; On the other hand, about 50% of the resources are reserved for projects with more mature mechanisms and shorter development cycles.

What Novo has truly announced on this Capital Market Day is not just a pipeline list, but a redefinition of its growth model: from relying on super single products such as semaglutide for high-speed growth in the past, to using multiple products, mechanisms, dosage forms, and price bands to cover a wider range of patients, and then using AI and organizational restructuring to compress the research and development cycle, while continuously supplementing the pipeline through external BD.

What Novo wants to switch is not actually a product, but a set of growth logic. However, this new logic requires time to be validated, and time is precisely its scarcest asset.