Novo Nordisk CagriSema Tops Eli Lilly Tirzepatide in Diabetes Trial

Novo Nordisk and Eli Lilly have spent years locked in a commercial and scientific rivalry over the fast growing market for GLP-1 and amylin based obesity and diabetes medicines. Novo Nordisk relies on semaglutide, sold as Ozempic for type 2 diabetes and Wegovy for weight management, while Eli Lilly built its franchise around tirzepatide, sold as Mounjaro for diabetes and Zepbound for obesity. Both face patent expiries after 2030 and both are investing in next generation injectables and oral formulations. Novo Nordisk has positioned CagriSema, a fixed dose combination of cagrilintide and semaglutide, as a potential successor to Wegovy.

The pressure intensified earlier this year. Clinical Trials Arena reported on February 23 that CagriSema had been outperformed by Eli Lilly Zepbound in a head to head obesity trial. The phase 3 REDEFINE 4 trial did not meet its primary endpoint of non inferiority on weight loss for CagriSema compared with Zepbound after 84 weeks. Patients treated with CagriSema 2.4 mg achieved 23.0% weight loss after 84 weeks compared with 25.5% for Zepbound 15 mg. Under a treatment regimen estimand, CagriSema produced 20.2% weight loss versus 23.6% for Zepbound. The trial included 809 adults with obesity and at least one comorbidity, with a mean baseline body weight of 114.2 kg. That result was widely viewed as a setback for Novo Nordisk in obesity.

On September 21, 2026, Novo Nordisk delivered a different result in diabetes. Reuters reported on September 21 that once weekly CagriSema 1.0 mg/1.0 mg produced an estimated average weight loss of 12.4% in a late stage trial in patients with type 2 diabetes, outperforming Eli Lilly tirzepatide. The comparison came from the phase 3 REIMAGINE 5 trial, which tested CagriSema 1.0 mg/1.0 mg against tirzepatide 5 mg in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both. The result reversed, at least in diabetes, the earlier head to head loss in obesity.

Novo Nordisk disclosed the data at its Capital Markets Day, alongside results from REDEFINE 9. The company also detailed a multi year rollout for its next generation obesity injectables, targeting a launch of the CagriSema combination early next year, according to Reuters. The announcement arrived as Novo Nordisk faces questions about pricing power and dealmaking ahead of patent expiries.

Key Facts

BioSpace reported on September 21 that Novo Nordisk said once weekly CagriSema 1.0 mg/1.0 mg was superior to tirzepatide 5 mg for weight loss in REIMAGINE 5, achieving average weight loss of 12.4% versus 9.1%. The release said CagriSema confirmed non inferior reduction in HbA1c of 1.71% versus 1.67% for tirzepatide. The dual primary endpoints were measured to week 60 in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both.

In REDEFINE 9, which tested CagriSema versus placebo as an adjunct to diet and exercise in participants with overweight or obesity, the 1.0 mg/1.0 mg dose produced 21.0% weight reduction at week 68 compared with 2.0% for placebo. The primary superiority endpoint was met. Novo Nordisk said CagriSema also showed greater improvements than placebo across prespecified supportive endpoints, including systolic blood pressure, waist to height ratio, and fasting lipid profile.

CagriSema combines cagrilintide, a long acting amylin receptor agonist, with semaglutide, a GLP-1 receptor agonist. It is an investigational product. Novo Nordisk filed a New Drug Application with the U.S. Food and Drug Administration in December 2025 for CagriSema for weight management, and a decision is expected in the fourth quarter of 2026.

Reuters reported on September 21 that Novo Nordisk U.S. listed shares were down more than 4% before the bell as analysts questioned the drugmaker pricing power and dealmaking strategy. BMO analyst Evan Seigerman said the low dose data was encouraging but less impactful, given that tirzepatide has already been proven superior to higher doses of CagriSema in obesity. The Biotech Times reported on September 23 that the REIMAGINE 5 comparison used tirzepatide 5 mg, the starting dose rather than the approved maximum of 15 mg, and that Novo Nordisk acknowledged not all patients reach or tolerate the highest doses, framing dose flexibility as a practical advantage.

Martin Holst Lange, executive vice president for research and development and chief scientific officer at Novo Nordisk, said in the September 21 announcement: 'With only 1.0 mg/1.0 mg, CagriSema shows superior weight loss versus tirzepatide 5 mg as well as strong results across obesity and type 2 diabetes. CagriSema remains investigational, but these findings strengthen our confidence in its potential, add to the growing evidence for amylin biology and reinforce our ambition to advance the next generation of treatments for obesity and type 2 diabetes.'

Analysis

The bigger picture here is that the September 21 result gives Novo Nordisk a credible narrative in type 2 diabetes while leaving important questions about obesity unanswered. In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg beat tirzepatide 5 mg on weight loss, 12.4% versus 9.1%, and matched it on blood sugar reduction, 1.71% versus 1.67%. But the comparison used tirzepatide at 5 mg, the starting dose, not the 15 mg maximum that Eli Lilly has studied and regulators have approved. Clinical Trials Arena reported on February 23 that the earlier REDEFINE 4 obesity trial, which compared CagriSema 2.4 mg with Zepbound 15 mg, went the other way: 23.0% weight loss for CagriSema versus 25.5% for Zepbound at 84 weeks. The contrast matters because it shows how sensitive the competitive picture is to dose selection and patient population.

Analysts have highlighted that sensitivity. Reuters reported on September 21 that BMO analyst Evan Seigerman called the low dose data encouraging but less impactful given tirzepatide prior superiority over higher doses of CagriSema in obesity. The market reaction reflected caution: Novo Nordisk U.S. listed shares fell more than 4% before the bell, according to Reuters, as investors focused on pricing power and dealmaking ahead of patent expiries after 2030. The share move shows that a phase 3 win in diabetes does not automatically translate into confidence about the broader obesity franchise.

There is also a strategic complication. The Biotech Times reported on September 23 that if CagriSema is approved on schedule, Novo Nordisk would enter a market that already includes semaglutide branded forms Ozempic and Wegovy as well as tirzepatide. That creates a situation in which Novo Nordisk competes with itself across two product lines. The company must persuade payers, physicians, and patients that CagriSema offers enough additional benefit to justify a new price, even though semaglutide is already familiar. The REDEFINE 9 result of 21.0% weight loss versus 2.0% for placebo at week 68 is strong, but the obesity market is no longer empty. Eli Lilly has its own next generation programs, and the broader GLP-1 and amylin segment is attracting investment in next generation incretin combinations, oral formulations, and once monthly dosing.

What this really means is that Novo Nordisk has bought itself a stronger hand in diabetes and a fresh set of questions in obesity. The company can point to a superiority win against tirzepatide in type 2 diabetes and to a large placebo controlled weight loss effect in REDEFINE 9. It cannot yet claim that CagriSema is the best obesity medicine against the highest approved dose of tirzepatide, because the September 21 diabetes trial did not test that question and the earlier obesity trial did not favor CagriSema. Novo Nordisk also mentioned promising results in painful diabetic neuropathy, according to The Biotech Times, which signals label expansion ambitions beyond weight and glycaemic control.

Why It Matters

For patients with type 2 diabetes, the REIMAGINE 5 data offer another potential option that combines amylin and GLP-1 biology in a single weekly injection. The trial met its dual primary endpoints: superiority on weight loss and non inferiority on HbA1c reduction. People with diabetes often struggle with weight and blood sugar at the same time, so a therapy that addresses both is clinically meaningful. The modest difference in HbA1c, 1.71% versus 1.67%, suggests that the two drugs are close on glycaemic control, while the weight difference of 12.4% versus 9.1% is more pronounced in this specific comparison.

For Novo Nordisk, the result is a partial answer to the REDEFINE 4 setback. CagriSema is viewed as a successor to Wegovy, which faces patent expiries after 2030. A win in diabetes keeps the product in the conversation and supports the company argument that amylin biology adds to semaglutide. It also supports Novo Nordisk ambition to advance the next generation of treatments, as Martin Holst Lange said. The company has filed for FDA approval in weight management, and a decision is expected in the fourth quarter of 2026.

For Eli Lilly, the trial is a reminder that tirzepatide at 5 mg is not the same as tirzepatide at 15 mg. Eli Lilly has built a strong position with Zepbound and Mounjaro, and the earlier REDEFINE 4 result showed that Zepbound 15 mg can beat CagriSema 2.4 mg in obesity. The September 21 diabetes data do not erase that. They do, however, show that dose for dose, CagriSema can compete. The competitive dynamic will depend on which doses are used, which populations are studied, and how regulators and payers weigh the evidence.

Next Up

Novo Nordisk expects an FDA decision on its CagriSema New Drug Application for weight management in the fourth quarter of 2026. The application was filed in December 2025. Reuters reported on September 21 that Novo Nordisk detailed a multi year rollout for its next generation obesity injectables and is targeting a launch of the CagriSema combination early next year. If approved, the product would enter a market that already includes Ozempic, Wegovy, Mounjaro, and Zepbound.

Further readouts and label expansion efforts will shape the next phase of the competition. Novo Nordisk mentioned promising results in painful diabetic neuropathy, according to The Biotech Times, and the broader segment continues to attract investment in next generation incretin combinations, oral formulations, and once monthly dosing. The key question for investors and clinicians is whether CagriSema can show a consistent advantage in obesity against the highest effective doses of tirzepatide, not only in diabetes at the starting dose. Until that question is answered, the September 21 win remains important but incomplete.