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

18 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 study team or your doctor.

What data supports the effectiveness of the drug CagriSema for obesity?

Research shows that semaglutide, a component of CagriSema, is effective in achieving significant and sustained weight loss in people with obesity. Additionally, cagrilintide, when combined with semaglutide, has shown promising results in further enhancing weight loss, making this combination a logical approach for effective weight management. ^{1 2 3 4 5}

Is CagriSema safe for humans?

Semaglutide, a component of CagriSema, is generally well-tolerated, but it can cause temporary stomach issues like nausea and diarrhea. No new safety concerns have been raised in recent trials, but long-term safety is still being studied. ^{5 6 7 8 9}

How is the drug CagriSema different from other obesity treatments?

CagriSema combines two drugs, semaglutide and cagrilintide, which work together to reduce appetite and promote weight loss more effectively than using either drug alone. This combination targets different pathways in the brain to help manage obesity, offering a novel approach compared to existing treatments. ^{2 3 5 10 11}

What is the purpose of this trial?

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 medicine that combines two medicines called cagrilintide and semaglutide. It is still being tested in studies and is not yet available for doctors to prescribe. Participants will get an injection with each of the two versions of CagriSema at two different times at the clinic. Like all medicines, the study medicine may have side effects. The study will last for about 18 weeks.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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.

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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 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 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]

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]

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 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]

References

1. England 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? [2022]

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

Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. [2023]

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

Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. [2023]

5. England 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. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. [2023]

8. England 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. [2022]

9. Switzerland 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. [2023]

10. England 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. [2023]

11. England 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. [2021]