CagriSema vs. Tirzepatide for Weight Loss in Obesity

Recruiting at 87 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

809 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug CagriSema for weight loss in obesity?

Research shows that tirzepatide, a component of CagriSema, is effective for weight loss, with studies indicating it can lead to significant weight reduction. Additionally, semaglutide, another component, is known for its weight-lowering effects, suggesting that CagriSema may be effective for weight loss in obesity. ^{1 2 3 4 5}

Is CagriSema or Tirzepatide safe for weight loss in obesity?

Tirzepatide and semaglutide, components of CagriSema, have been studied for safety in humans, showing similar side effects like nausea, vomiting, diarrhea, and constipation, especially at higher doses. Cardiovascular safety has been demonstrated, with no increased risk of major cardiovascular events. These treatments have been used for type 2 diabetes and obesity, indicating a general safety profile in these conditions. ^{1 2 3 4 6}

How does the drug CagriSema differ from other obesity treatments?

CagriSema combines cagrilintide and semaglutide, offering a unique approach by targeting both appetite regulation and glucose control, potentially enhancing weight loss compared to other treatments. Tirzepatide, another component, acts on two receptors to lower glucose and appetite, showing promising weight loss results similar to or better than existing GLP-1 receptor agonists. ^{2 3 5 7 8}

What is the purpose of this trial?

This trial tests if a new combination of two drugs, given regularly, helps people lose weight better than another treatment. It targets individuals needing to lower their body weight by helping them feel less hungry and manage their weight. Two different drugs are being investigated as options for weight management.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

An update on peptide-based therapies for type 2 diabetes and obesity. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Tirzepatide: A novel, first-in-class, dual GIP/GLP-1 receptor agonist. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. [2023]

7. England 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. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. [2023]