Novo Nordisk Pins Recovery Hopes on CagriSema Combination Therapy

Facing intense competitive pressure, Novo Nordisk is making a strategic push to reclaim its leadership in the lucrative obesity drug market. The Danish pharmaceutical giant has submitted a key regulatory application for its combination therapy, CagriSema, following a period of significant share price weakness. This move represents a critical component of the company's broader plan to counter the growing threat from rival Eli Lilly.

Novo Nordisk's stock has faced substantial headwinds. Over the past twelve months, the share price has fallen sharply, trading approximately 58% below its 52-week high. Since the start of the year, the decline totals roughly 52%. The shares recently closed at 41.08 euros, hovering just above their annual low.

This downturn is largely attributed to mounting concerns over the company's ability to defend its dominant obesity market position against Eli Lilly. Lilly's GLP-1 medications, Zepbound and Mounjaro, have captured meaningful market share. While analysts suggest CagriSema's efficacy is comparable to Zepbound, they note Lilly may hold advantages regarding injection site reactions.

FDA Submission for a Novel Combination

On December 18, 2025, Novo Nordisk filed a New Drug Application (NDA) with the U.S. Food and Drug Administration for CagriSema. The candidate is a once-weekly injectable combination of cagrilintide (2.4 mg) and semaglutide (2.4 mg), intended for chronic weight management in adults with obesity or overweight who have at least one weight-related comorbidity.

If approved, CagriSema would become the first available injection combining a GLP-1 receptor agonist with an amylin analogue. The treatment is designed to be used alongside a reduced-calorie diet and increased physical activity to achieve and sustain weight loss.

CEO Mike Doustdar characterized the submission as a "significant milestone" and a potential "new chapter in weight management," underscoring its strategic importance to the firm's portfolio.

Robust Clinical Data Supports Application

The regulatory filing is backed by compelling data from two Phase III programs within the REDEFINE clinical trial series.

Should investors sell immediately? Or is it worth buying Novo Nordisk?

REDEFINE 1: Demonstrating Substantial Weight Loss
This study involved 3,417 adults with obesity or overweight over a 68-week treatment period. Key outcomes include:
* Participants receiving CagriSema achieved an average weight reduction of 20.4% of their body weight, compared to just 3% for the placebo group.
* Among patients who completed the full study period, weight loss reached 22.7% versus 2.3% with placebo.
* Approximately 91.9% of the CagriSema group lost at least 5% of their body weight, a milestone achieved by only 31.5% of the placebo group.
* About 54% of participants who began the trial with obesity fell below the clinical threshold for obesity after 68 weeks.

REDEFINE 2: Focusing on a High-Risk Population
This trial evaluated 1,206 adults with type 2 diabetes alongside obesity or overweight, assessing efficacy and safety in this relevant cohort. While specific efficacy figures were not disclosed in the summary, the data were included in the NDA, indicating Novo Nordisk views the results as robust enough for regulatory purposes.

Safety Profile Aligns with Drug Class Expectations
The safety data for CagriSema aligns with the known profile of GLP-1-based therapies, with gastrointestinal events being the most common adverse reactions.
* Discontinuation rates due to side effects were 5.9% (CagriSema) vs. 3.5% (placebo) in REDEFINE 1, and 8.4% vs. 3% in REDEFINE 2.
* Frequent side effects (CagriSema vs. placebo) included nausea (55% vs. 12.6%), constipation (30.7% vs. 11.6%), and vomiting (26.1% vs. 4.1%).

Broader Corporate Restructuring Underway

The CagriSema application is part of a series of major corporate developments:
* A complete overhaul of the board of directors by the Novo Nordisk Foundation in November 2025.
* The appointment of Mike Doustdar as Chief Executive Officer in August 2025.
* The completion of a $5.2 billion acquisition of Akero Therapeutics on December 9, 2025, expanding the metabolic and liver disease pipeline.
* A separate FDA application for a higher 7.2 mg dose of Wegovy, submitted on November 26, 2025.

These actions signal a concerted effort to broaden and technologically upgrade the company's obesity and metabolic portfolio to structurally compete with Eli Lilly.

Upcoming Catalysts for Investors

Several near-term milestones will be crucial for Novo Nordisk's trajectory:
* CagriSema FDA Review: A decision is expected in 2026 and will be a key indicator of the company's future competitive standing.
* Oral Semaglutid: An FDA verdict on the tablet form of semaglutide is anticipated before the end of 2025.
* Higher-Dose Wegovy: The 7.2 mg version is also under review by U.S. regulators.
* Q4 2025 Earnings: Financial results are scheduled for release on February 4, 2026.

The coming months will reveal whether Novo Nordisk's regulatory and strategic initiatives can successfully lay the groundwork for a operational recovery and stem the recent decline in its equity value.