CagriSema for Type 2 Diabetes

(REIMAGINE 2 Trial)

Recruiting at 657 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Metformin, SGLT2 inhibitors

Must not be taking: Insulin, other diabetes drugs

Disqualifiers: Renal impairment, Uncontrolled retinopathy, 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

2734 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You can continue taking your current diabetes medications, like metformin and possibly an SGLT2 inhibitor, while participating in the trial. However, you cannot take other diabetes or obesity medications not listed in the inclusion criteria within 90 days before starting the trial.

What data supports the effectiveness of the drug CagriSema for type 2 diabetes?

Research shows that combining semaglutide with cagrilintide (CagriSema) has weight-loss benefits, and semaglutide alone is effective in controlling blood sugar levels in type 2 diabetes patients, often better than other common treatments. ^{1 2 3 4 5}

Is CagriSema safe for humans?

Semaglutide, a component of CagriSema, has been studied extensively and is generally safe for humans, though it may cause gastrointestinal side effects like nausea. It has been associated with an increased risk of eye problems in people with existing diabetic eye disease. ^{3 5 6 7 8}

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

CagriSema is unique because it combines two components: semaglutide, which helps lower blood sugar and weight, and cagrilintide, a long-acting amylin analogue that also aids in weight loss. This combination may offer enhanced weight-loss benefits compared to using semaglutide alone. ^{1 3 6 9 10}

What is the purpose of this trial?

This trial tests CagriSema, a combination of semaglutide and cagrilintide, in people with type 2 diabetes. It aims to see if it can better manage blood sugar levels and reduce body weight by increasing insulin and reducing hunger. Semaglutide is known for lowering blood glucose levels and reducing appetite.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for adults with type 2 diabetes who have been diagnosed for at least 180 days, have an HbA1c level of 7.0-10.5%, and are on a stable dose of metformin with or without SGLT2 inhibitors. Participants should also have a BMI of at least 25 kg/m^2. Those with severe kidney issues, unstable diabetic eye disease, or recent use of other diabetes/obesity meds (except short-term insulin) cannot join.

Inclusion Criteria

My BMI is 25 or higher.

I have been on a stable dose of metformin, with or without SGLT2 inhibitors, for over 90 days.

I am either male or female.

Exclusion Criteria

I have unstable diabetic eye problems confirmed by a recent eye exam.

My kidney function is severely impaired.

I haven't taken diabetes or obesity drugs, except short insulin uses, in the last 90 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive once-weekly subcutaneous injections of study medications or placebo for 68 weeks

68 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

Treatment Details

Interventions

• CagriSema
• Placebo cagrilintide
• Placebo semaglutide
• Semaglutide

Trial Overview The study tests CagriSema—a combination drug including semaglutide and cagrilintide—against each component alone and a placebo to see how well it lowers blood sugar and body weight in people taking their usual diabetes medication.

Participant Groups

Group I: CagriSema Dose 2 Experimental Treatment 2 Interventions

Participants will receive once-weekly s.c injections of cagrilintide dose 2 and semaglutide dose 2 for 68 weeks.

Group II: CagriSema Dose 1 Experimental Treatment 2 Interventions

Participants will receive once-weekly subcutaneous (s.c) injections of cagrilintide dose 1 and semaglutide dose 1 for 68 weeks.

Group III: Semaglutide Dose 1 Active Control 1 Intervention

Participants will receive once-weekly s.c injection of semaglutide dose 1 for 68 weeks.

Group IV: Semaglutide Dose 2 Active Control 1 Intervention

Participants will receive once-weekly s.c injection of semaglutide dose 2 for 68 weeks.

Group V: Cagrilintide Dose 1 Active Control 1 Intervention

Participants will receive once-weekly s.c injection of cagrilintide dose 1 for 68 weeks.

Group VI: Placebo Dose 1 Placebo Group 2 Interventions

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

Group VII: Placebo Dose 2 Placebo Group 2 Interventions

Participants will receive once-weekly s.c injection of placebo matched to cagrilintide dose 2 and semaglutide dose 2 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 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]

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]

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]

In a network meta-analysis of 26 randomized controlled trials, subcutaneous semaglutide (1 mg once-weekly) significantly reduced HbA1c and fasting blood glucose levels compared to placebo, demonstrating its efficacy in managing type 2 diabetes.

While semaglutide showed comparable safety to placebo, it was associated with higher rates of gastrointestinal adverse events, particularly at doses of 0.8 mg and in comparison to tirzepatide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. Zaazouee, MS., Hamdallah, A., Helmy, SK., et al.[2022]

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]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively lower hemoglobin A1c levels by approximately -1.5% and reduce body weight by about -4.5 kg in phase 3 trials, demonstrating comparable efficacy to dulaglutide.

While semaglutide offers cardiovascular benefits, including a reduced risk of major cardiovascular events, it is associated with an increased risk of retinopathy complications in patients with existing diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. Miles, KE., Kerr, JL.[2021]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

In a meta-analysis of 23 randomized trials involving 22,096 patients with type 2 diabetes, semaglutide was not found to significantly increase the overall risk of diabetic retinopathy (DR) compared to control groups.

However, the analysis indicated that semaglutide was associated with a higher risk of DR in specific subgroups, particularly in patients aged 60 years or older and those with a diabetes duration of 10 years or more, suggesting that caution is warranted in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Wang, F., Mao, Y., Wang, H., et al.[2022]

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

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

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. [2022]

5. 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]

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

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. [2021]

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

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

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

Semaglutide: First Global Approval. [2019]

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

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. [2022]