Novo's CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial

Phase 3 data position investigational CagriSema as a potent weight-loss option versus tirzepatide and placebo ahead of an expected FDA decision in late 2026.

Rhea-AI Summary

Novo Nordisk (NVO) reported phase 3 topline results showing once-weekly CagriSema 1.0 mg/1.0 mg achieved 12.4% weight loss versus 9.1% with tirzepatide 5 mg at week 60 in adults with type 2 diabetes in the REIMAGINE 5 trial.

CagriSema also delivered a non-inferior HbA1c reduction of 1.71% versus 1.67% for tirzepatide. In the REDEFINE 9 obesity trial, CagriSema 1.0 mg/1.0 mg produced 21.0% weight loss versus 2.0% with placebo at week 68, meeting the primary superiority endpoint and improving prespecified measures such as systolic blood pressure, waist-to-height ratio and fasting lipid profile. Across both trials, CagriSema was well tolerated overall, with a safety profile consistent with earlier studies. Novo Nordisk has filed a CagriSema New Drug Application for weight management with a US FDA decision expected in Q4 2026.

Positive

• Weight loss 12.4% vs. 9.1% for CagriSema vs. tirzepatide 5 mg at week 60 in type 2 diabetes
• HbA1c reduction 1.71% vs. 1.67% for CagriSema vs. tirzepatide, meeting non-inferiority
• Weight loss 21.0% vs. 2.0% for CagriSema vs. placebo at week 68 in obesity
• Supportive endpoints improved including systolic blood pressure, waist-to-height ratio and fasting lipid profile vs. placebo
• Safety profile described as well tolerated overall and consistent with previous CagriSema studies
• NDA filed for CagriSema in weight management, with US FDA decision expected in Q4 2026

Negative

• None.

Market Context

NVO had a +0.12% pre-headline move, while the momentum scanner listed no peers, so the supplied mark...

Analysis

NVO had a +0.12% pre-headline move, while the momentum scanner listed no peers, so the supplied market data showed no same-direction peer confirmation for these Phase 3 results.

Key Figures

Weight loss: 12.4% vs. 9.1% HbA1c reduction: 1.71% vs. 1.67% Weight reduction: 21.0% vs. 2.0% +1 more

Weight loss

12.4% vs. 9.1%

REIMAGINE 5 at week 60; CagriSema vs. tirzepatide

HbA1c reduction

1.71% vs. 1.67%

REIMAGINE 5 at week 60; CagriSema vs. tirzepatide

Weight reduction

21.0% vs. 2.0%

REDEFINE 9 at week 68; CagriSema vs. placebo

FDA decision timing

Q4 2026

Expected decision on the CagriSema weight-management application

Key Terms

hba1c, non-inferior, amylin receptor agonist, glp-1 receptor agonist, +1 more

5 terms

hba1c medical

"CagriSema also confirmed non-inferior reduction in HbA1c"

A1c (HbA1c) is a blood test that measures how much sugar has stuck to red blood cells over the past two to three months, giving a single number that reflects average blood glucose control—think of it as a running average score for blood sugar. Investors watch A1c because it’s a common clinical measure used to judge whether diabetes drugs, devices or care programs work, influence regulatory approvals, treatment guidelines and market demand.

non-inferior medical

"confirmed non-inferior reduction in HbA1c"

Non-inferior describes a result from a clinical or comparative test showing a new product, treatment, or approach is not meaningfully worse than an existing standard by more than an agreed-upon, acceptable difference. Think of it like proving a new car model performs at least close enough to the old one on key measures so consumers won’t lose out. Investors care because non-inferiority outcomes can clear regulatory or market hurdles and preserve commercial potential without needing to beat the incumbent.

amylin receptor agonist medical

"a long-acting amylin receptor agonist, cagrilintide"

An amylin receptor agonist is a drug that activates the body’s amylin receptors to mimic the hormone amylin, which helps slow stomach emptying, reduce appetite, and regulate blood sugar. For investors, these medicines matter because clinical trial results, safety profiles, and regulatory approval determine their commercial potential in diabetes and obesity markets—similar to how a new feature can change a product’s appeal and sales prospects.

glp-1 receptor agonist medical

"and a GLP-1 receptor agonist, semaglutide"

A GLP-1 receptor agonist is a medicine that mimics a natural gut hormone to trigger insulin release, slow stomach emptying, and curb appetite — like using a key to turn on a lock that controls blood sugar and hunger signals. For investors, these drugs matter because they treat common conditions such as diabetes and obesity, can drive large prescription and sales growth, reshape healthcare costs, and heavily affect drug pipelines, competition and company valuations.

efficacy estimand technical

"Based on efficacy estimand"

An efficacy estimand is the precise definition of the treatment effect a clinical trial aims to measure — who is being measured, what outcome counts, and how events like missed doses or additional medicines are handled. Think of it as the exact recipe and rules for measuring a cake’s taste so different tasters and interruptions don’t muddy the result. Investors care because the estimand determines how convincing and comparable trial results are, which directly affects regulatory decisions, market expectations, and valuation risk.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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• CagriSema 1.0 mg/1.0 mg achieved superior weight loss of 12.4%* versus tirzepatide 5 mg of 9.1%* and non-inferior HbA_1c reduction at week 60 in adults with type 2 diabetes in REIMAGINE 5.
• CagriSema 1.0 mg/1.0 mg delivered significant and clinically meaningful weight loss of 21%* versus placebo at week 68 in adults living with overweight or obesity in REDEFINE 9. In both trials, CagriSema was well tolerated overall, with a safety profile consistent with previous studies.
  

Bagsværd, Denmark, 21 September 2026 – Novo Nordisk today announced topline results from the phase 3 REIMAGINE 5 and REDEFINE 9 trials of once-weekly CagriSema (cagrilintide and semaglutide), an investigational product, and Novo's next innovation in weight management and type 2 diabetes. The findings were highlighted at Novo’s Capital Markets Day investor briefing.

In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg was superior to tirzepatide 5 mg for weight loss, achieving an estimated average weight loss of 12.4%, compared with 9.1%, respectively. CagriSema also confirmed non-inferior reduction in HbA_1c (1.71%) versus tirzepatide (1.67%).

In REDEFINE 9, CagriSema 1.0 mg/1.0 mg provided a weight reduction of 21.0% versus 2.0% for placebo, and the primary superiority endpoint was met. CagriSema also showed greater improvements than placebo across prespecified supportive endpoints, including systolic blood pressure, waist-to-height ratio and fasting lipid profile.

“The results from CagriSema are very encouraging, demonstrating the strong potency of the combination of semaglutide and cagrilintide. 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,” said Martin Holst Lange, executive vice president, Research & Development and chief scientific officer at Novo. “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."

Treatment decisions in obesity and type 2 diabetes are often individualised, and not all patients receive or remain on the highest available dose of current therapies. These data provide important evidence of the potential of CagriSema 1.0 mg/1.0 mg, and expand our understanding of how efficacy, tolerability and dose flexibility may support individualised care.

Also during Capital Markets Day, Novo presented data on painful diabetic neuropathy in type 2 diabetes for the first time, showing promising results. More details will be presented at a later time.

Trial key results

Trial	Population	Treatment	Primary Endpoints	Key Results
REIMAGINE 5	Adults with type 2 diabetes (inadequately controlled on metformin, SGLT2i, or both)	CagriSema 1.0 mg/1.0 mg vs. tirzepatide 5 mg	1) Change in HbA1c 2) Relative change in body weight (week 60)	Weight loss: 12.4% (CagriSema) vs. 9.1% (tirzepatide) – superior HbA1c reduction: 1.71% (CagriSema) vs. 1.67% (tirzepatide) – non-inferior
REDEFINE 9	Adults with overweight or obesity (adjunct to diet & exercise)	CagriSema 1.0 mg/1.0 mg vs. placebo	1) Relative change in body weight 2) Proportion achieving ≥5% weight reduction (week 68)	Weight loss: 21.0% (CagriSema) vs. 2.0% (Placebo) – superior

About the REIMAGINE 5 trial
REIMAGINE 5 was a phase 3 trial investigating once-weekly CagriSema 1.0 mg/1.0 mg compared with tirzepatide 5 mg in participants with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both. The dual primary endpoints were change in HbA_1c and relative change in body weight from baseline to week 60.

About the REDEFINE 9 trial
REDEFINE 9 was a phase 3 trial investigating once-weekly CagriSema 1.7 mg/1.7 mg and CagriSema 1.0 mg/1.0 mg compared with placebo, as an adjunct to a reduced-calorie diet and increased physical activity, in participants living with overweight or obesity. The primary endpoints were relative change in body weight and the proportion of participants achieving at least 5% body-weight reduction from baseline to week 68.

About CagriSema
Once-weekly subcutaneous CagriSema is being investigated by Novo as a treatment for adults with overweight or obesity (REDEFINE programme) and as a treatment for adults with type 2 diabetes (REIMAGINE programme). CagriSema is a fixed-dose combination of a long-acting amylin receptor agonist, cagrilintide, and a GLP-1 receptor agonist, semaglutide.

Novo filed a New Drug Application with the U.S. Food and Drug Administration in December 2025 for CagriSema for weight management, demonstrating the company's commitment to lasting health innovation in obesity. A decision is expected in Q4 2026.

Novo is the global healthcare company that believes lasting health starts now. For over a century, we’ve combined leading scientific expertise with a deep understanding of people’s lives. We develop treatments and support that help millions of people make progress they can see, feel and sustain now and in the future. Every day, over 67,000 employees around the world advance our purpose to drive change for lasting health. Through our partnerships, programmes and investments, we’re working to prevent disease, expand access to treatments and reduce our environmental impact to help even more people live healthier lives. For more information, visit novonordisk.com and follow us on Instagram, LinkedIn, TikTok, Facebook, X and YouTube.

Contacts for further information

Novo Media:
Ambre James-Brown +45 3079 9289 globalmedia@novonordisk.com	Liz Skrbkova (US) +1 609 917 0632 USMediaRelations@novonordisk.com
Novo Investors:
Michael Novod +45 3075 6050 nvno@novonordisk.com	Sina Meyer +45 3079 6656 azey@novonordisk.com
Christoffer Togo Solgaard-Tullin +45 3079 1471 cftu@novonordisk.com
Ida Schaap Melvold +45 3077 5649 idmg@novonordisk.com	Mads Berner Bruun +45 3075 2936 mbbz@novonordisk.com
Frederik Taylor Pitter (US) +1 609 613 0568 fptr@novonordisk.com	Alex Bruce (US) +1 640 230 0276 axeu@novonordisk.com

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*Based on efficacy estimand

Attachment

• PR260921-CagriSema-CMD-2026

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What populations were studied in the REIMAGINE 5 and REDEFINE 9 trials?

REIMAGINE 5 enrolled adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both. REDEFINE 9 enrolled adults living with overweight or obesity who received CagriSema or placebo as an adjunct to a reduced-calorie diet and increased physical activity.

What doses of CagriSema were evaluated in these phase 3 studies?

Both trials evaluated once-weekly subcutaneous CagriSema 1.0 mg/1.0 mg. REDEFINE 9 also investigated a 1.7 mg/1.7 mg CagriSema dose versus placebo, although topline weight-loss results highlighted the 1.0 mg/1.0 mg arm.

What were the primary endpoints and timeframes for REIMAGINE 5 and REDEFINE 9?

In REIMAGINE 5, the dual primary endpoints were change in HbA1c and relative change in body weight from baseline to week 60. In REDEFINE 9, the primary endpoints were relative change in body weight and the proportion of participants achieving at least 5% body-weight reduction from baseline to week 68.

What is CagriSema and in which programmes is it being developed?

CagriSema is an investigational once-weekly fixed-dose combination of the long-acting amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. It is being studied for adults with overweight or obesity in the REDEFINE programme and for adults with type 2 diabetes in the REIMAGINE programme.

When is a US regulatory decision on CagriSema expected?

Novo Nordisk filed a New Drug Application with the US Food and Drug Administration for CagriSema in weight management in December 2025, and a decision is expected in the fourth quarter of 2026.