CagriSema for Obesity

Not currently recruiting at 46 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a new medication, CagriSema (a combination of cagrilintide and semaglutide), aids weight loss in people with obesity compared to a placebo ("dummy medicine"). Participants will be randomly assigned to receive either CagriSema or the placebo for the first two years. In the third year, those who took the placebo will switch to CagriSema. Individuals with a body mass index (BMI) of 35 or higher and without diabetes may be suitable for this study. Like all medicines, CagriSema may have side effects, and its effectiveness and safety remain under investigation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking obesity treatment.

Will I have to stop taking my current medications?

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

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

Studies have shown that the combination of two treatments, Cagrilintide and Semaglutide, known as CagriSema, is generally well-tolerated. Research indicates that this combination leads to significant weight loss. In one study, 91.9% of participants lost at least 5% of their body weight. Notably, CagriSema has been linked to fewer cases of vomiting compared to similar treatments.

While all medicines can have side effects, evidence so far suggests that CagriSema is safe for many people. This information can reassure those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about CagriSema for obesity because it combines two active ingredients, cagrilintide and semaglutide, into a single treatment which could enhance weight loss effectiveness. Unlike most current treatments that typically focus on appetite suppression or metabolism, CagriSema brings together the unique actions of a long-acting amylin analog (cagrilintide) and a GLP-1 receptor agonist (semaglutide) to potentially offer more comprehensive control of hunger and energy balance. This dual-action approach could not only help people lose weight more effectively but also maintain that weight loss over a longer period, addressing a significant challenge in obesity management.

What evidence suggests that CagriSema might be an effective treatment for obesity?

Research has shown that CagriSema, a combination of cagrilintide and semaglutide, is highly effective for weight loss. In one study, participants lost an average of 20.4% of their body weight over 68 weeks. Another study found that some individuals lost up to 22.7% of their weight. Notably, 91.9% of participants lost at least 5% of their weight, and more than half lost 20% or more. In this trial, participants will receive either CagriSema or a placebo. These results suggest that CagriSema could significantly aid weight loss in individuals with 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?

This trial is for people with obesity who haven't had success with other weight loss methods. Participants should be adults willing to follow the study procedures for three years. Specific medical conditions or treatments may disqualify some individuals, but these details are not provided here.

Inclusion Criteria

* Male or female.

* Body mass index (BMI) greater than or equal to (\>=) 35.0 kilograms per meter square (kg/m\^2).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Treatment

Participants receive either CagriSema or placebo for weight loss over a 2-year period

104 weeks

Extension

Participants receive CagriSema or a dose tapering of CagriSema for those who had it in the main phase, or start CagriSema if they had placebo

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Semaglutide

Trial Overview The trial is testing CagriSema, a new medication by Novo Nordisk, against a placebo over three years. The first two years (main phase) participants receive either CagriSema or placebo randomly. In the final year (extension phase), those on CagriSema might have their dose reduced while others switch from placebo to CagriSema.

How Is the Trial Designed?

Group I: CagriSema Experimental Treatment 2 Interventions

Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) after a dose escalation period of 16 weeks during the maintenance period for 88 weeks in the main phase. Participants randomised to this arm will be included in the extension phase for one year.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously once weekly for 104 weeks. Participants randomised to this arm will be included in the extension phase for one year.

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

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]

In a 32-week trial with 92 participants, the combination of semaglutide and cagrilintide (CagriSema) led to a significant reduction in HbA1c levels compared to cagrilintide alone, indicating improved glycemic control in individuals with type 2 diabetes.

CagriSema also resulted in greater weight loss compared to both semaglutide and cagrilintide, demonstrating its potential as an effective treatment option for managing weight and blood sugar levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias, JP., Deenadayalan, S., Erichsen, L., et al.[2023]

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]

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 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]

Semaglutide 2.4 mg led to significant weight loss in adults with overweight/obesity, achieving a mean change of -15.7% for those on antidepressants compared to -0.2% for placebo, demonstrating its efficacy regardless of antidepressant use.

The safety profile of semaglutide was consistent with previous studies, showing a similar prevalence of adverse events between the semaglutide and placebo groups among participants taking antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis. Kushner, RF., Fink-Jensen, A., Frenkel, O., et al.[2023]

Semaglutide 2.4 mg, administered weekly, can lead to significant weight loss (average 9.6-17.4% of initial body weight) over 68 weeks, improving obesity-related health issues.

While semaglutide is effective, healthcare providers must evaluate patient suitability carefully, considering factors like safety, potential side effects, and individual health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

Semaglutide 2.4 mg has been shown to be effective for weight loss in overweight and obese individuals, including those with type 2 diabetes, outperforming all pharmacological comparators in a systematic review of 41 randomized controlled trials.

Participants taking semaglutide were more likely to lose at least 5% of their baseline body weight after 12 weeks of treatment compared to those on other weight management medications, indicating its strong efficacy in promoting significant weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis. Smith, I., Hardy, E., Mitchell, S., et al.[2022]

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]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[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]

In a meta-analysis of six randomized controlled trials involving 3962 overweight or obese individuals, subcutaneous semaglutide 2.4 mg administered weekly resulted in significant and sustainable weight loss, with an average reduction of 11.8% in body weight compared to placebo.

Semaglutide was well tolerated, with the most common side effects being mild to moderate gastrointestinal issues, indicating a favorable safety profile for non-diabetic overweight or obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial. Qin, W., Yang, J., Deng, C., et al.[2023]

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. 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, ...

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. the-innovation.org the-innovation.org/article/doi/10.59717/j.xinn-med.2025.100150

The next frontier in metabolic health: Cagrilintide-Semaglutide ... Notably, an impressive 91.9% of patients in the combination therapy group achieved at least 5% weight loss, with 53.6% achieving ≥20% and 34.7% achieving ≥25% ...

5. docwirenews.com docwirenews.com/post/cagrilintide-and-semaglutide-combo-highly-effective-for-weight-loss

Cagrilintide and Semaglutide Combo Highly Effective for ... The analysis revealed that participants receiving cagrilintide plus semaglutide achieved a mean 20.4% reduction in body weight at 68 weeks, ...

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.