CagriSema vs. Tirzepatide for Weight Loss in Obesity

Not currently recruiting at 89 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 84 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, CagriSema and Tirzepatide, in helping people with obesity lose weight. CagriSema is a new medicine that combines Cagrilintide and Semaglutide and is not yet available from doctors. Participants will receive weekly injections under the skin, with doses gradually increasing to the planned amount. The trial lasts about a year and a half. Eligible participants are adults with a body mass index (BMI) of 30 or more who do not have diabetes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking obesity treatments.

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 trial coordinators or your doctor.

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

Research shows that both CagriSema and Tirzepatide hold promise for weight loss and are safe for individuals with obesity.

For CagriSema, studies have found that a weekly combination of cagrilintide and semaglutide leads to significant weight loss. Previous studies indicate that this combination is generally well-tolerated. The most common side effects were mild, such as nausea and vomiting, and these often decreased over time as the body adjusted to the medication.

Regarding Tirzepatide, research indicates it also aids in weight loss and is generally safe. Participants experienced similar side effects to CagriSema, with nausea being the most common. Again, these side effects usually lessen with continued use.

Both treatments have undergone thorough testing and have shown a good safety profile. This suggests they are safe for use, though participants should remain aware of potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments CagriSema and Tirzepatide for obesity because they represent fresh approaches to weight loss. CagriSema is a combination of cagrilintide and semaglutide, which leverages the benefits of both a long-acting amylin analog and a GLP-1 receptor agonist to enhance weight loss, potentially offering a dual mechanism of action that current treatments don't provide. On the other hand, Tirzepatide, a dual GIP and GLP-1 receptor agonist, has been shown to support significant weight reduction by mimicking natural hormones that regulate appetite and food intake. Unlike standard treatments like lifestyle changes and medications that target only one pathway, these innovative drugs aim to provide more robust weight management options.

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

This trial will compare the effectiveness of CagriSema and Tirzepatide for weight loss in individuals with obesity. Research has shown that CagriSema, a combination of cagrilintide and semaglutide, can help people lose a significant amount of weight. In studies, individuals without diabetes lost up to 22.7% of their weight, while those with type 2 diabetes lost about 15.7%. This combination led to an additional 5.5% to 8.9% weight loss compared to semaglutide alone.

Tirzepatide, another treatment option in this trial, has also demonstrated strong results. Most participants using Tirzepatide lost at least 5% of their weight, with some studies showing an average weight loss of 18.3% over 72 weeks. Both treatments have shown promising results for weight loss, but CagriSema might help some individuals lose more weight. ^{1 2 3 4 6}

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 adults with obesity, defined as having a BMI of 30 or higher. It's not suitable for people who have diabetes (type 1 or type 2) or those with an HbA1c level of 6.5% or more, which indicates high blood sugar levels.

Inclusion Criteria

I am either male or female.

Body mass index (BMI) of ≥ 30.0 kilogram per square meter (kg/m^2)

Exclusion Criteria

I have a history of diabetes.

Glycated haemoglobin (HbA1c) ≥ 6.5 % (48 millimoles per mole [mmol/mol]) as measured by the central laboratory at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous injections of either CagriSema or Tirzepatide, with a dose escalation period followed by maintenance dosing

84 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Semaglutide
• Tirzepatide

Trial Overview

The study compares the effectiveness of CagriSema—a combination of two drugs, Cagrilintide and Semaglutide—with Tirzepatide in helping individuals lose weight. Participants will self-administer weekly injections using a pen injector over approximately one and a half years.

How Is the Trial Designed?

Group I: CagriSema 2.4 mg/2.4 mg Experimental Treatment 2 Interventions

Participants will receive 2.4 mg cagrilintide and 2.4 mg semaglutide subcutaneously once-weekly (dose escalation period of 16 weeks) for up to 84 weeks.

Group II: Tirzepatide 15 mg Active Control 1 Intervention

Participants will receive 15 mg tirzepatide subcutaneously once-weekly (dose escalation period of 20 weeks) for up to 84 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

Tirzepatide, a novel drug that activates both GLP-1 and GIP receptors, shows glucose-lowering and weight loss effects that are at least as effective as traditional GLP-1 receptor agonists, based on a review of studies leading to its approval.

Current evidence suggests that tirzepatide may be more effective than GLP-1 RAs for weight loss, indicating it could become the preferred treatment option for patients with or without diabetes who want to lose weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. Andraos, J., Muhar, H., Smith, SR.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Long-acting GLP-1 analogues, such as semaglutide and tirzepatide, have shown significant efficacy in lowering blood glucose and body weight, making them promising treatments for type 2 diabetes and obesity.

The increasing demand for GLP-1R agonists like liraglutide and semaglutide has led to shortages, prompting a prioritization of their use in diabetes therapy over obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on peptide-based therapies for type 2 diabetes and obesity. Bailey, CJ., Flatt, PR., Conlon, JM.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Oral semaglutide at doses of 7 mg and 14 mg significantly reduced hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes, with reductions of 1.06% and 1.10% respectively compared to placebo, based on a meta-analysis of 11 randomized controlled trials involving 9821 patients.

Both doses of semaglutide also led to significant weight loss, but the 14 mg dose was associated with a higher incidence of gastrointestinal side effects, such as nausea and vomiting, leading to more medication discontinuations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. Li, A., Su, X., Hu, S., et al.[2023]

Tirzepatide, a once-weekly medication for type 2 diabetes, not only improves blood sugar control but also leads to significant weight loss and positive changes in cardiovascular health, such as reduced blood pressure and improved insulin sensitivity.

The weight loss and metabolic benefits of tirzepatide are linked to its dual action as a GIP and GLP-1 receptor agonist, suggesting that these mechanisms play a crucial role in its effectiveness for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. Várkonyi, TT., Pósa, A., Pávó, N., et al.[2023]

Tirzepatide, a new GLP-1 receptor agonist, was found to be more effective for weight loss compared to other GLP-1RAs like semaglutide and liraglutide, with significant weight loss observed in over 12,300 patients in the analysis.

While all GLP-1RAs were associated with gastrointestinal side effects, tirzepatide showed better efficacy outcomes for weight loss while maintaining a similar safety profile to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. Alkhezi, OS., Alahmed, AA., Alfayez, OM., et al.[2023]

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