Novo Nordisk's CagriSema Fails to Outperform Competitors in Weight Loss Trials, Stock Drops

Novo Nordisk's next-generation weight loss drug, CagriSema, has recently disappointed investors with its latest trial results, which failed to demonstrate superior efficacy compared to existing medications. CagriSema contains a novel weight loss therapy component known as a pancreatic polypeptide analog, representing one of the Danish pharmaceutical company's bets in the burgeoning obesity drug market.

Despite the setback, there remains a debate within the industry regarding the broader applications and effects of weight loss drugs beyond overall weight reduction. Novo Nordisk's ambition to usher in a new era of obesity treatment with CagriSema has been called into question following a series of trial results that led to a decline in its stock price.

Earlier this month, the primary results of the late-stage REDEFINE-2 trial showed that Novo Nordisk's next-generation drug, CagriSema, helped obese or overweight adult patients with type 2 diabetes lose 15.7% of their weight over 68 weeks, compared to a 3.1% weight loss in the placebo group. This result fell short of the previously predicted weight loss percentage of over 15%.

An earlier late-stage trial released in December last year indicated that the drug helped obese or overweight patients with one or more comorbidities (but not type 2 diabetes) lose 22.7% of their weight over 68 weeks, also below the expected 25%. Both results contributed to a significant drop in Novo Nordisk's stock price, as investors' hopes for a superior alternative to the company's existing Wegovy injection and competitor Eli Lilly's Zepbound (both GLP-1 class drugs) were dashed.

CagriSema is a combination drug consisting of cagrilintide (a novel weight loss therapy component known as a pancreatic polypeptide analog) and semaglutide (the active ingredient in Wegovy). The drug was hoped to provide better weight loss outcomes for diabetes patients, who typically struggle to lose weight with existing GLP-1 class treatments. However, the 15.7% weight loss result in the REDEFINE-2 trial was disappointing.

Analysts had previously believed that CagriSema's pancreatic polypeptide component could potentially demonstrate superior weight loss effects compared to Zepbound. However, the results showed that CagriSema's effects were similar to those of semaglutide (Sema) and Zepbound across both obese patients and obese diabetic patients. These results were deemed insufficient to withstand future competition.

Concerns also remain regarding CagriSema's tolerability, as only less than two-thirds of patients were able to reach the maximum dose after 68 weeks. Novo Nordisk stated that CagriSema is "well-tolerated," with the most common adverse reactions being gastrointestinal, which were described as mild to moderate and decreased over time.

Investors are seeking the best-in-class treatment option to secure Novo Nordisk's position in the weight loss drug market. The upcoming REDEFINE-4 study, scheduled to release results in early 2026, may provide more information on the drug's efficacy over a longer period and with more flexible dosing regimens, potentially setting it apart from competitors.

Despite the setbacks, the weight loss treatment field continues to expand, with various companies aiming to enter the market. The market is expected to exceed $100 billion by 2030. However, investors and patients will have to wait for these products to hit the market, with Zealand Pharma's Petrelintide expected to launch around 2030. Novo Nordisk plans to submit a regulatory approval application for CagriSema in the first quarter of 2026.

Nevertheless, the company still has some ground to cover to regain the previous enthusiasm surrounding the drug. When asked if investors would consider CagriSema as one of the potential replacements for existing blockbuster drugs, analysts remained cautious but optimistic that they eventually would.