CagriSema for Type 2 Diabetes

(REIMAGINE 2 Trial)

Not currently recruiting at 801 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called CagriSema to evaluate its effectiveness in helping people with type 2 diabetes manage blood sugar and weight. CagriSema combines two existing medicines, semaglutide and cagrilintide, and is taken once a week. The trial compares CagriSema to each medicine individually and to a placebo (a dummy treatment with no active ingredients). This trial is for individuals who have had type 2 diabetes for at least 6 months and are currently taking metformin, with or without an SGLT2 inhibitor, to manage their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatment CagriSema, which combines cagrilintide and semaglutide, has been tested for safety and effectiveness in people with type 2 diabetes. In earlier studies, no deaths occurred while using CagriSema, suggesting it is safe and encouraging for those considering joining the trial.

Studies have found semaglutide to be generally safe. For instance, only 0.5% of patients experienced serious side effects, and 5.1% stopped using it due to side effects, indicating most people handle semaglutide well.

Similarly, cagrilintide has undergone safety testing and shown positive results. One study found it helped people lose weight without serious safety issues.

Overall, both semaglutide and cagrilintide, whether used alone or together as CagriSema, appear well-tolerated, with no serious safety problems reported in the studies mentioned. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CagriSema for Type 2 Diabetes because it combines two active ingredients, cagrilintide and semaglutide, offering a novel approach to managing the condition. Unlike standard treatments that often focus solely on glucose control, CagriSema targets both blood sugar levels and appetite regulation, potentially leading to better overall metabolic health. Additionally, its once-weekly subcutaneous injection format provides convenience, which could improve patient adherence compared to other daily medications. This dual-action mechanism and ease of use set CagriSema apart from traditional diabetes therapies.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

Studies have shown that CagriSema, a combination of semaglutide and cagrilintide, helps people with type 2 diabetes control blood sugar and lose weight. Research indicates that CagriSema can lead to weight loss of up to 15.7% in these individuals. This trial will test different doses of CagriSema, as well as semaglutide and cagrilintide individually. Semaglutide alone reduces body weight and improves blood sugar, with studies showing most people lose at least 5% of their weight. Cagrilintide by itself led to about a 9.7% weight loss after 26 weeks. Overall, CagriSema shows promise in managing type 2 diabetes by effectively lowering blood sugar and aiding weight loss. ^{1 2 3 4 6}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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]

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]

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]

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]

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]

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]

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]

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. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)01163-7/fulltext

Efficacy and safety of co-administered once-weekly ... In people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37364590/

Efficacy and safety of co-administered once-weekly ... Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06065540

NCT06065540 | A Research Study to See How Well ... The study will look at how well CagriSema helps people lower their blood sugar and body weight. CagriSema is a new weekly medicine that combines two ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05394519

A Research Study to See How Well CagriSema Helps ... This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight.