CagriSema for Obesity

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Must not be taking: Amylin analogues

Disqualifiers: Pregnancy, High HbA1c, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two versions of a new medicine called CagriSema, a combination of cagrilintide and semaglutide, to assess their effects on blood levels. Researchers are studying CagriSema for obesity treatment, but it is not yet available for prescription. Participants will receive injections of each version at different times over the 18-week trial. This trial may suit adults with a BMI between 27.0 and 39.9, where excess weight is primarily due to body fat. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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 treatment is likely to be safe for humans?

Earlier studies have tested the combination of cagrilintide and semaglutide, known as CagriSema, for weight loss. Research shows that this treatment has led to significant weight reduction. Specifically, one study found a weight loss of up to 22.7% in adults without diabetes and 15.7% in those with type 2 diabetes.

Regarding safety, studies suggest that the treatment is generally well-tolerated. Although specific side effects are not listed here, it is important to note that the treatment remains in the early testing stages. As a result, safety information is still being collected, and participants might experience some side effects as the treatment undergoes further study. Nonetheless, the promising weight loss results suggest potential benefits that balance these risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CagriSema for obesity because it combines two active ingredients, cagrilintide B and semaglutide I, which work together in a novel way. Unlike traditional treatments that mostly focus on appetite suppression, this combination targets both appetite control and metabolism. The use of a pen-injector for delivery is also noteworthy, as it offers a convenient and precise dosing method. This dual-action approach and user-friendly delivery system set CagriSema apart from existing options like GLP-1 receptor agonists and other appetite suppressants.

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

Research has shown that combining two medicines, cagrilintide and semaglutide, known as CagriSema, can lead to significant weight loss. In one study, participants taking CagriSema lost up to 22.7% of their body weight. Another study found that 91.9% of participants lost at least 5% of their weight. These medicines work better together than alone, enhancing weight loss. This trial will evaluate two different sequences of CagriSema administration to determine its effectiveness for those struggling with obesity. ^{1 2 3 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 adults with overweight or obesity. Participants will receive injections of two different versions of a medication called CagriSema, which combines cagrilintide and semaglutide, at separate times. The study aims to compare the blood levels of these medications after injection.

Inclusion Criteria

Body Mass Index (BMI) between 27.0 and 39.9 kg/m^2 at screening, overweight should be due to excess adipose tissue as judged by the investigator

My health, based on recent tests and exams, qualifies me for the trial.

Exclusion Criteria

I have been treated with an amylin analogue before.

Known or suspected hypersensitivity to study intervention(s) or related products

Glycosylated haemoglobin (HbA1c) >= 6.5 percent (48 mmol/mol) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive a single subcutaneous dose of CagriSema in one of the two versions

1 day

1 visit (in-person)

Washout

A washout period to clear the drug from the system before the next treatment

7 weeks

Treatment Period 2

Participants receive a single subcutaneous dose of the alternate version of CagriSema

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CagriSema

Trial Overview The trial is testing two versions of CagriSema (labeled as 'CagriSema A' and 'Cagrilintide B with Semaglutide I') to see how they affect blood levels of cagrilintide and semaglutide in participants. It's designed to determine if there are differences between the two formulations.

How Is the Trial Designed?

Group I: Treatment sequence 2 Experimental Treatment 2 Interventions

Participants will receive a single s.c. dose of CagriSema A in PDS290 pen-injector in period 1 followed by a single s.c. dose of CagriSema (cagrilintide B and semaglutide I) in DV3384 pen-injector in period 2 separated by a wash out period of minimum 7 weeks.

Group II: Treatment sequence 1 Experimental Treatment 2 Interventions

Participants will receive a single subcutaneous (s.c.) dose of CagriSema (cagrilintide B and semaglutide I) in DV3384 pen-injector in period 1 followed by a single s.c. dose of CagriSema A in PDS290 pen-injector in period 2 separated by a wash out period of minimum 7 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

In a post hoc analysis of the SUSTAIN 1-3 trials involving 2432 participants with type 2 diabetes, semaglutide significantly reduced body weight (BW) by 3.7 to 6.1 kg compared to comparators, which only saw reductions of 1.0 to 1.9 kg.

The improvement in insulin resistance (IR) was primarily linked to weight loss, with 70% to 80% of the IR reduction from semaglutide 0.5 mg and 34% to 94% from semaglutide 1.0 mg being mediated by the decrease in BW.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. Fonseca, VA., Capehorn, MS., Garg, SK., et al.[2023]

In a phase 1b trial involving 96 healthy participants, the combination of cagrilintide and semaglutide 2.4 mg was well tolerated, with most adverse events being mild to moderate, indicating a favorable safety profile for this weight management treatment.

Cagrilintide doses of 1.2 mg and 2.4 mg resulted in significant body weight reductions of 15.7% and 17.1%, respectively, compared to a placebo group, suggesting that this combination therapy may be effective for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Enebo, LB., Berthelsen, KK., Kankam, M., et al.[2021]

A total of 5,442 cases of gastrointestinal adverse events (AEs) associated with semaglutide were identified, with 45 signals detected, indicating a range of gastrointestinal issues, including 17 new and unexpected signals.

The study found that patient age and body weight were significant factors influencing the severity of gastrointestinal AEs, with a median time-to-onset of 23 days for strong signals, suggesting that while risks exist, they may decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. Shu, Y., He, X., Wu, P., et al.[2023]

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]

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]

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]

A study analyzing 31,542 adverse event reports from the FDA found that semaglutide, a GLP-1 analogue, has a higher potential for misuse and abuse compared to other GLP-1 receptor agonists, with significant reporting odds ratios for issues like drug abuse and withdrawal syndrome.

The findings suggest that semaglutide may be misused as a weight-loss treatment in non-obese individuals, highlighting the need for further research to fully understand its safety profile and the implications of its use outside of approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset. Chiappini, S., Vickers-Smith, R., Harris, D., et al.[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]

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]

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 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. 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.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40544432/

Cagrilintide-Semaglutide in Adults with Overweight or ... Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 ...

4. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/combining-cagrilintide-with-semaglutide-amplifies-weight-loss-outcomes/

Combining Cagrilintide With Semaglutide Amplifies Weight ... The proportion of individuals who achieved at least a 5% weight reduction was 91.9% with combined semaglutide and cagrilintide compared with ...

5. acc.org acc.org/Latest-in-Cardiology/Journal-Scans/2025/07/02/14/43/REDEFINE-1-and-REDEFINE-2

REDEFINE 1 and REDEFINE 2: Greater Weight Loss With ... CagriSema recipients were more likely to achieve weight-loss targets of ≥5%, ≥20%, ≥25%, and ≥30% (p<0.001 for all comparisons) vs. placebo.

6. 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 ...

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.