CagriSema for Type 2 Diabetes and Obesity

(REDEFINE 2 Trial)

Recruiting at 304 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Oral antidiabetics

Disqualifiers: Pregnancy, Renal impairment, Hypoglycaemia, 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

1200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that your current diabetes medications remain stable for at least 90 days before joining. So, you should not stop taking them if you want to participate.

What data supports the effectiveness of the drug CagriSema for Type 2 Diabetes and Obesity?

Research shows that combining semaglutide with cagrilintide (CagriSema) has weight-loss benefits, and semaglutide alone has been effective in providing significant and sustained weight loss in obesity, which can help manage type 2 diabetes. Additionally, oral semaglutide has been shown to improve blood sugar control and reduce body weight in patients with type 2 diabetes. ^{1 2 3 4 5}

Is CagriSema safe for humans?

Semaglutide, a component of CagriSema, has been shown to be generally safe in humans, with the most common side effects being temporary stomach issues. It has been tested in people with type 2 diabetes and obesity, and no new safety concerns have been raised in recent trials. ^{3 6 7 8 9}

What makes the drug CagriSema unique for treating type 2 diabetes and obesity?

CagriSema combines semaglutide, a drug that helps with weight loss and reduces insulin resistance, with cagrilintide, an amylin agonist that enhances weight loss. This combination aims to provide greater and more sustained weight loss than semaglutide alone, offering a novel approach to managing type 2 diabetes and obesity. ^{2 10 11 12 13}

What is the purpose of this trial?

This trial tests if the new medicine CagriSema can help people with excess body weight and type 2 diabetes lose weight. Participants will receive either CagriSema or another treatment. The study will last about a year and a half. Cagrilintide and semaglutide are both being investigated for weight management.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

Adults with type 2 diabetes and a BMI of at least 27.0 kg/m^2 can join this study if they've been on stable oral diabetic medication for the past 90 days and have an HbA1c level between 7%-10%. They shouldn't be pregnant, breastfeeding, or planning pregnancy during the trial. People with severe kidney issues, recent serious hypoglycemia, or unstable diabetic eye problems cannot participate.

Inclusion Criteria

I am either male or female.

I was diagnosed with type 2 diabetes more than 6 months ago.

Your HbA1c level is between 7% and 10% as measured by the central laboratory at screening.

Exclusion Criteria

I don't have unstable diabetic eye problems as checked by a recent eye exam.

I haven't had severe low blood sugar or unnoticed low blood sugar episodes in the last 6 months.

My kidney function is low, with an eGFR below 30.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CagriSema or placebo once weekly for weight loss and diabetes management

68 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

Treatment Details

Interventions

• Cagrilintide
• Placebo cagrilintide
• Placebo semaglutide
• Semaglutide

Trial Overview The trial is testing CagriSema—a new medicine—against placebo versions to see how well it helps people with excess body weight and type 2 diabetes lose weight. Participants will receive either the real drug or a dummy version randomly over about one and a half years.

Participant Groups

Group I: CagriSema Experimental Treatment 2 Interventions

Cagrilintide + semaglutide once weekly

Group II: Placebo Placebo Group 2 Interventions

Placebo cagrilintide + semaglutide once weekly

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 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]

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]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

In a phase 3 trial involving 388 treatment-naive patients with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.45% with 0.5 mg and 1.55% with 1.0 mg doses compared to placebo, indicating its efficacy in improving glycaemic control.

Semaglutide also led to significant weight loss, with reductions of 3.73 kg and 4.53 kg for the respective doses, while maintaining a safety profile similar to existing GLP-1 receptor agonists, with most adverse events being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Sorli, C., Harashima, SI., Tsoukas, GM., et al.[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]

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]

In the SUSTAIN 1 to 5 trials involving 3918 participants with type 2 diabetes, semaglutide significantly helped more individuals achieve their HbA1c targets (47% to 74%) compared to placebo (7% to 19%) and other active comparators (16% to 29%).

Semaglutide was effective in achieving these results while minimizing unwanted outcomes, such as weight gain, severe hypoglycaemia, and gastrointestinal side effects, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. DeVries, JH., Desouza, C., Bellary, S., et al.[2022]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[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]

Semaglutide, approved by the FDA on June 4, 2021, is the first new drug for chronic weight management in adults with obesity or overweight since 2014, specifically targeting those with a BMI of 27 or greater and at least one weight-related condition.

This medication is intended to be used alongside a weight management program that includes a reduced-calorie diet and increased physical activity, highlighting its role as part of a comprehensive approach to weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Mares, AC., Chatterjee, S., Mukherjee, D.[2023]

References

1. 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]

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

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

3. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. [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. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. [2022]

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

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

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

Semaglutide for the treatment of obesity. [2023]

12. 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]

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

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. [2023]