CagriSema After the “Trial Miss”: What Comes Next for Novo

Copenhagen traders didn’t require translation on the morning the data was released. Years of post-Wegovy euphoria were erased as Novo Nordisk shares fell, and screens glowed red across dealing desks. Bicycles leaned against railings in the gray winter weather outside the glass towers, and inside, analysts revised models that had assumed Novo still held the future of obesity medicine just weeks before.

At first glance, the numbers themselves did not appear to be very bad. Over the course of 84 weeks, CagriSema caused about 23% weight loss, which would have seemed miraculous ten years ago. However, miracles are rated on a curve in the current obesity-drug arms race. Comparable studies showed that Zepbound, Eli Lilly’s tirzepatide therapy, showed about 25% or more, and that small margin suddenly appeared to be decisive.

Apparently, investors think efficacy is predetermined. If a medication aids in weight loss, doctors will recommend it, insurance companies will favor it, and patients looking through social media reviews will specifically request it. Why anyone would pick Novo’s medication over the more effective incumbent was openly questioned by analysts. It’s a chilly calculus that combines elements of psychology and science.

Nearly instantly, Novo’s leadership, especially CEO Mike Doustdar, resisted. He referred to the competitor’s performance as a “abnormality” and maintained that CagriSema is still an effective treatment. Whether this is a near-miss or a misinterpreted success, Novo seems to be debating the narrative as much as the numbers.

There is more than one molecule in CagriSema. It combines cagrilintide, an amylin analogue that suppresses appetite in a different way, with semaglutide, the GLP-1 engine that powers Wegovy. Theoretically, the combination more closely resembles the body’s natural satiety signals. The trial’s outcome in practice points to synergy, though maybe not enough to take over.

It’s difficult not to observe how expectations have changed as you watch the response play out. When Wegovy was introduced in 2021, its weight-loss results astounded doctors and made Novo the most valuable company in Europe. Discussions about currency, real estate markets, and Denmark’s pension funds all started to revolve around the company’s success. The same business is now defending a medication that, in a different time period, would have been revolutionary.

Novo isn’t backing down. The business has already submitted an application for U.S. approval, and a decision is anticipated in late 2026. Perceptions could still be altered by more trials, such as REDEFINE 11 and a higher-dose study. Doustdar suggested that Wegovy’s efficacy was increased by higher dosage, which raised the possibility that the same pattern would manifest here. Dosing strategy may end up being more important than molecular design.

Nevertheless, the pressure from competition is growing. Eli Lilly is promoting a triple-hormone treatment that has been shown in trials to reduce weight by almost 28%. Should those outcomes persist, the efficacy bar will rise once more. Small changes can have a significant commercial impact in a market where consumers are motivated by obvious outcomes, such as decreasing waistlines and viral before-and-after pictures.

Novo seems to understand this fact. The business has indicated that it is open to future agreements after spending $2 billion to acquire the rights to an experimental treatment from a Chinese developer. Even though they are risky, acquisitions have the potential to speed up pipeline depth more quickly than internal development alone. Investors might favor decisive action over gradual advancement.

When semaglutide exclusivity starts to wane in the early 2030s, there is also the patent horizon. CagriSema was meant to close that gap and keep Novo at the top for the ensuing ten years. Analysts now wonder if it is capable of carrying that burden.

However, it seems premature to declare the medication obsolete. In a world where obesity is the primary cause of diabetes, cardiovascular disease, and rising health-system costs, a treatment that results in a 23% weight loss is still clinically meaningful. Tolerability, ease of dosing, and patient adherence—aspects that seldom make the front page of trial summaries—may still be important to doctors.

But clean hierarchies—first place, second place, and irrelevance—are preferred by markets. It is rare for that binary logic to hold up when dealing with actual patients and clinics. Whether the obesity market will support several winners or converge around a single dominant therapy is still up in the air.

The selling slowed late in the afternoon in Copenhagen. The screens remained steady. Over the low industrial skyline of Bagsvaerd, where Novo’s laboratories are tucked away behind security gates and hedges, the winter light dimmed. Scientists continue to hone molecules and dosing curves inside those buildings in an effort to make tiny improvements that could change markets worth billions of dollars.

As this develops, it seems that Novo’s problem is no longer solely a scientific one. Convincing physicians, patients, and investors that finishing second in a trial does not equate to finishing second in the future is a psychological, strategic, and even cultural endeavor.