CagriSema for Obesity

Recruiting at 23 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes, others

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: 68 weeks

300 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 obesity?

Research shows that semaglutide, a component of CagriSema, is effective in causing 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 potentially effective treatment for obesity. ^{1 2 3 4 5}

Is CagriSema safe for humans?

Semaglutide, a component of CagriSema, is generally well tolerated in humans, with the most common side effects being temporary stomach issues like nausea. Long-term studies have not raised new safety concerns, but ongoing monitoring is important to fully understand its safety. ^{5 6 7 8 9}

How is the drug CagriSema unique for treating obesity?

CagriSema combines two drugs, semaglutide and cagrilintide, which work together to reduce appetite and promote weight loss. This combination targets different pathways in the brain to enhance the feeling of fullness, making it a novel approach compared to other treatments that typically focus on a single mechanism. ^{2 3 5 10 11}

What is the purpose of this trial?

This study will look at how well CagriSema helps people with excess body weight lose weight. CagriSema is a new medicine developed by Novo Nordisk that combines cagrilintide and semaglutide. CagriSema cannot yet be prescribed by doctors. In the study, participant will either get CagriSema or dummy medicine and which treatment participant get is decided by chance. The study will last for about 1½ years for each participant.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for individuals with excess body weight, commonly referred to as obesity. Participants will be randomly assigned to receive either the experimental medication CagriSema or a placebo (dummy medicine) and will participate in the study for approximately 1½ years.

Inclusion Criteria

I am either male or female.

Body Mass index (BMI) greater than or equal to (≥) 30.0 kilogram per meter square (kg/m^2) or BMI ≥27.0 kg/m2 with the presence of at least one obesity related complication including, but not limited to hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease

Exclusion Criteria

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

I have a history of diabetes (type 1 or 2).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-weekly subcutaneous injections of CagriSema or placebo for weight loss, with dose escalation over 8-12 weeks and maintenance for up to 60-68 weeks

68 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• CagriSema

Trial Overview The effectiveness of different doses of CagriSema, a new combination drug made up of cagrilintide and semaglutide by Novo Nordisk, is being tested. The goal is to determine how well it helps people lose weight compared to a placebo.

Participant Groups

Group I: CagriSema Dose 1 Experimental Treatment 2 Interventions

Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 8-week dose escalation period until target dose (dose 1) of CagriSema (cagrilintide and semaglutide) is achieved and maintained up to 60 weeks.

Group II: CagriSema Dose 2 Active Control 2 Interventions

Participants will receive once-weekly s.c injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 12-week dose escalation period until target dose (dose 2) of CagriSema(cagrilintide and semaglutide) is achieved and maintained up to 56 weeks.

Group III: Placebo Dose 2 Placebo Group 1 Intervention

Participants will receive once-weekly s.c injection of placebo matched to cagrisema dose 2 (cagrilintide and semaglutide) for 68 weeks.

Group IV: Placebo Dose 1 Placebo Group 1 Intervention

Participants will receive once-weekly s.c injection of placebo matched to cagrisema dose 1 (cagrilintide and semaglutide) for 68 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]

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]

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]

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]

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 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. 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]

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

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

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

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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