CagriSema for Obesity

(REDEFINE 1 Trial)

Not currently recruiting at 496 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 68 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new weight-loss treatment, CagriSema (a combination of Semaglutide and Cagrilintide), compared to other treatments and a placebo ("dummy" medicine). Participants will receive one of four treatments, including CagriSema, to determine which is most effective for weight loss. The trial targets adults with a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher if they have health issues related to being overweight, such as high blood pressure or sleep apnea. This trial may suit those struggling with excess weight and related health problems. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study staff or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial are generally well-tolerated. Studies have found that CagriSema helps adults with obesity lose significant weight without serious safety concerns. Some participants experienced mild side effects, such as nausea, but these were not severe.

Cagrilintide alone is similarly safe. It has been tested in adults with obesity and has demonstrated effective weight loss, with fewer side effects like vomiting compared to other treatments.

Semaglutide is already approved for weight loss under a different name. Studies show it is effective but can cause mild side effects like nausea and diarrhea, which are usually temporary and manageable.

Overall, the treatments in this trial have undergone previous testing and are considered safe for most people. Participants can expect some mild side effects, but serious issues are rare. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CagriSema for obesity because it combines two active ingredients, cagrilintide and semaglutide, which work together to target and manage weight loss. Unlike traditional weight loss medications that often focus on appetite suppression or fat absorption, CagriSema utilizes the unique combination of these ingredients to enhance satiety and improve metabolic control. Cagrilintide, an amylin analogue, and semaglutide, a GLP-1 receptor agonist, both play roles in regulating appetite and weight, offering a potential new approach to obesity management that could be more effective than using either agent alone.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will evaluate different treatment arms for managing obesity. Participants in one arm will receive CagriSema, a combination of cagrilintide and semaglutide. Studies have shown this combination can help people lose up to 22.7% of their body weight. Another arm will test cagrilintide alone, which proved effective in previous studies, with patients losing about 9.7% of their weight by week 26. A separate arm will evaluate semaglutide alone, which has shown weight loss results between 14.9% and 17.4% in people without type 2 diabetes. These treatments offer promising options for managing obesity. ^{1 3 5 6 7}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

Adults with a BMI of at least 30, or at least 27 with weight-related health issues like high blood pressure or sleep apnea can join. It's not for those who have diabetes or an HbA1c level of 6.5% or higher.

Inclusion Criteria

Body mass index (BMI) greater than or equal to 30.0 kilograms per square meter (kg/m^2) or BMI greater than or equal to 27.0 kg/m^2 with the presence of at least one weight-related comorbidity including, but not limited to hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease

I am either male or female.

Exclusion Criteria

Glycaemia related: Glycated Haemoglobin (HbA1c) greater than or equal to 6.5 percent (48 millimoles per mole [mmol/mol]) as measured by the central laboratory at screening

I have a history of diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of four study medicines, including CagriSema, cagrilintide, semaglutide, or placebo, with weekly injections for weight loss

68 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants who continue in the extension study are monitored for changes in body weight and related diseases without receiving study medicine

97 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Placebo Cagrilintide
• Placebo Semaglutide
• Semaglutide

Trial Overview The trial is testing CagriSema against placebo and two other drugs, cagrilintide and semaglutide, to see which helps more with weight loss. Participants get one injection weekly by chance and are monitored for about 1.5 years, followed by a 2-year extension study without medication.

How Is the Trial Designed?

Group I: Cagrisema Experimental Treatment 2 Interventions

Participants will receive cagrilintide and semaglutide once-weekly after a dose escalation period of 16 weeks during the maintenance period for 52 weeks in the main phase. Participants randomised to this arm will be included in the extension phase for 97 weeks.

Group II: Cagrilintide Active Control 2 Interventions

Participants will receive cagrilintide s.c. and placebo matching to semaglutide once-weekly after a dose escalation period of 16 weeks during the maintenance period for 52 weeks.

Group III: Semaglutide Active Control 2 Interventions

Participants will receive semaglutide s.c.and placebo matched to cagrilintide once-weekly after a dose escalation period of 16 weeks during the maintenance period for 52 weeks.

Group IV: Placebo s.c. Placebo Group 2 Interventions

Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide once weekly for 68 weeks. Participants randomised to this arm will be included in the extension phase for 97 weeks.

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide, approved by the FDA on June 4, 2021, is the first new drug for chronic weight management in adults with obesity or overweight since 2014, specifically targeting those with a BMI of 27 or greater and at least one weight-related condition.

This medication is intended to be used alongside a weight management program that includes a reduced-calorie diet and increased physical activity, highlighting its role as part of a comprehensive approach to weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Mares, AC., Chatterjee, S., Mukherjee, D.[2023]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

Obesity is a major public health concern, with projections indicating that over 1.1 billion individuals will be affected by 2030, highlighting the urgent need for effective treatments.

GLP-1 receptor agonists, particularly semaglutide, are at the forefront of clinical development for obesity treatment, showing promise in improving metabolic health and potentially serving as a benchmark for future anti-obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Jepsen, MM., Christensen, MB.[2022]

Cagrilintide, an amylin-analog, is being developed alongside semaglutide, a GLP-1 receptor agonist, to enhance weight loss in individuals with obesity, leveraging their complementary mechanisms to reduce appetite.

Clinical trials have shown that both cagrilintide alone and in combination with semaglutide lead to promising weight loss results, supporting the potential of this combination therapy for effective long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. D'Ascanio, AM., Mullally, JA., Frishman, WH.[2023]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

In the STEP clinical trial program, participants with obesity who received once-weekly semaglutide 2.4 mg experienced significant weight loss, averaging between 14.9% and 17.4% over 68 weeks, with 69%-79% achieving at least 10% weight loss compared to only 12%-27% with placebo.

Semaglutide 2.4 mg also led to improvements in cardiometabolic risk factors and had a consistent safety profile, primarily involving gastrointestinal side effects, indicating its potential as an effective treatment for obesity and related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. Bergmann, NC., Davies, MJ., Lingvay, I., et al.[2023]

Subcutaneous semaglutide (Wegovy) has been shown to significantly reduce body weight in overweight and obese individuals, with a dose-dependent effect observed in four Phase 3 trials involving 5000 participants.

While semaglutide resulted in greater weight loss compared to placebo, gastrointestinal side effects were the most common safety concerns, highlighting the need for further studies in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of subcutaneous semaglutide for obesity. Phillips, A., Clements, JN.[2022]

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

In a 20-week trial with 72 adults, once-weekly subcutaneous semaglutide 2.4 mg significantly reduced appetite and energy intake, leading to a 9.9% reduction in body weight compared to only 0.4% with placebo.

Semaglutide improved participants' control over eating and reduced food cravings without causing delayed gastric emptying, indicating its efficacy in managing obesity without adverse effects on gastric function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Friedrichsen, M., Breitschaft, A., Tadayon, S., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2502081

Coadministered Cagrilintide and Semaglutide in Adults ... In a phase 2 trial, cagrilintide at a dose of 2.4 mg led to a 9.7% weight reduction by week 26. Because the combination of therapies with ...

2. sciencehub.novonordisk.com sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/easd2025/garvey1/documents/Garvey_EASD25_REDEFINE_1_Cagrilintide_Short_oral_with_disclosures.pdf

Efficacy and safety of cagrilintide 2.4 mg in adults with ... Efficacy and safety of cagrilintide 2.4 mg in adults with overweight/obesity: Data from REDEFINE 1. W. Timothy Garvey1*, Lei Liu2, John ...

3. diabetes.org diabetes.org/newsroom/press-releases/cagrisema-demonstrates-significant-weight-loss-adults-obesity

CagriSema Demonstrates Significant Weight Loss in Adults ... Once-weekly medication results in weight loss of up to 22.7% in adults without diabetes and 15.7% in those with type 2 diabetes.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40544433/

Coadministered Cagrilintide and Semaglutide in Adults ... Conclusions: Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, ...

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06716307

NCT06716307 | A Research Study to Compare Blood ... This study will compare the blood levels of cagrilintide and semaglutide when the same dose is given in two different versions of CagriSema. CagriSema is a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39676787/

Efficacy and Safety of Cagrilintide Alone and in ... Cagrisema outperforms semaglutide regarding weight loss. Cagrilintide shows comparable weight loss to semaglutide/liraglutide with significantly lower vomiting.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05394519

NCT05394519 | A Research Study to See How Well ... This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight.