Novo Takes Aim at Lilly’s Zepbound in Head-to-Head Trial Versus Wegovy Combo

Novo Nordisk_iStock, hapabapa

Pictured: Novo Nordisk's office in California/iStock, hapabapa

Novo Nordisk on Wednesday launched a new head-to-head Phase III trial, pitting its next-generation weight-loss combo therapy CagriSema against Eli Lilly’s newly approved Zepbound (tirzepatide).

According to the database, the new Phase III study will enroll 800 participants with obesity, excluding those with diabetes, and will wrap up in the second half of 2025. Its main outcome measure is relative change in body weight through 72 weeks of treatment. The study is also designed to evaluate waist circumference, blood pressure and lipid profile as well as safety.

CagriSema is an investigational obesity treatment that combines Novo’s best-selling product Wegovy (semaglutide) with cagrilintide, a long-acting analog of the pancreatic polypeptide amylin, which promotes weight loss by delaying gastric emptying and lowering blood glucose levels.

In August 2022, Novo posted Phase II data for CagriSema, touting 15.6% body weight reduction in overweight type 2 diabetes. This was numerically better when compared to individual injections for Wegovy or cagrilintide alone, which resulted in a 5.1% and 8.1% weight reduction, respectively.  CagriSema injections likewise lowered HbA1c levels to a greater degree.

Martin Lange, Novo’s executive vice president and head of development, revealed during the company’s third-quarter earnings report that CagriSema has recently entered the Phase III REIMAGINE program in type 2 diabetes.

With last week’s approval of Lilly’s Zepbound for chronic weight management in adults, the weight-loss drug space has become an even more heated race between the Indianapolis-based pharma and the Danish drugmaker. Zepbound’s challenge to Wegovy’s market footing opens with a price tag that is potentially around 20% lower.

Lilly in April 2023 also launched its own head-to-head study, dubbed SURMOUNT-5, testing Mounjaro (tirzepatide)—which is indicated for type 2 diabetes and shares the same active ingredient as Zepbound—against Wegovy in around 700 overweight or obese patients with weight-related comorbidities but without type 2 diabetes. SURMOUNT-5 is slated to be completed in late 2024.

Analysts expect the obesity market in the U.S. to continue its explosive growth in the coming years, with some estimating that it could reach up to $200 billion in value. The Novo-Lilly duopoly is expected to capture around 80% of this market by 2030.

In the third quarter of 2023, Novo’s Wegovy raked in $1.3 billion in revenue, a massive 730% in growth. During the same period, Lilly’s Mounjaro took in $1.4 billion.

Other pharma companies are also eyeing a slice of the multibillion-dollar obesity market. Last week, AstraZeneca inked an exclusive licensing contract with Shanghai-based biotech Eccogene for an investigational oral GLP-1 receptor agonist—dubbed ECC5004—being developed for obesity, type 2 diabetes and other cardiometabolic diseases.

The potential $2 billion deal puts AstraZeneca in the same arena as Lilly and Novo, though far behind its competitors. ECC5004 is currently in a Phase I study in the U.S.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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