CagriSema for Type 2 Diabetes

(REIMAGINE 1 Trial)

Not currently recruiting at 63 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must not be taking: Diabetes medications

Disqualifiers: Pregnancy, Renal impairment, 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: 40 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 determine if it helps people with type 2 diabetes lower their blood sugar and body weight. Participants will receive either CagriSema (a combination of Semaglutide and Cagrilintide) or a placebo (a "dummy" medicine with no active ingredients) through injections. The study compares different doses of CagriSema to assess its effectiveness. Suitable candidates for this trial have type 2 diabetes, struggle with managing blood sugar levels, and have a body mass index (BMI) of 23 or higher. 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.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking any medication for diabetes or obesity 90 days before screening, except for short-term insulin treatment for up to 14 days or insulin for gestational diabetes.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any diabetes or obesity medications at least 90 days before joining the trial, except for short-term insulin treatment for up to 14 days or insulin for gestational diabetes.

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

Research has shown that CagriSema, a combination of cagrilintide and semaglutide, is generally safe for patients. Together, these medicines help people lose significant weight, regardless of whether they have type 2 diabetes.

The treatment has undergone previous testing, and the results are encouraging. Participants using CagriSema reported fewer side effects than when taking each medicine alone, suggesting the combination might be gentler on the body.

Some participants experienced side effects like nausea, but these were manageable. These findings come from earlier trials, which ensure the treatment's safety before wider use. For those considering joining a trial, these studies indicate that the treatment has been carefully reviewed for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

CagriSema is unique because it combines two active ingredients, cagrilintide and semaglutide, which work together to manage type 2 diabetes. Unlike the standard treatments that often focus solely on insulin regulation or glucose absorption, CagriSema targets both appetite control through cagrilintide and blood sugar regulation via semaglutide. This dual-action approach may offer a more comprehensive management of diabetes, potentially leading to better overall outcomes for patients. Researchers are excited about this combination because it could provide enhanced efficacy in weight management and glucose control compared to existing options like metformin or insulin therapy alone.

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

Research has shown that CagriSema, a combination of cagrilintide and semaglutide, may help treat type 2 diabetes. In this trial, participants will receive different doses of CagriSema or a placebo. Studies have found that CagriSema can lead to significant weight loss, up to 15.7%, in people with type 2 diabetes. It also helps control blood sugar, which is crucial for managing diabetes. Reports indicate other health benefits, such as lower blood pressure and a smaller waist size. Overall, evidence suggests that CagriSema effectively helps manage both weight and blood sugar levels in people with type 2 diabetes. ^{1 2 5 6 7}

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 people with type 2 diabetes who manage their condition through diet and exercise. Participants will be involved in the study for about a year, receiving either the investigational medicine CagriSema or a placebo.

Inclusion Criteria

HbA1c 7.0-9.5 percent (53-80 mmol/mol) as determined by central laboratory at screening

I am either male or female.

I was diagnosed with type 2 diabetes more than 30 days ago.

Exclusion Criteria

My kidney function is low, with a filtration rate under 30 ml/min.

I am pregnant, breastfeeding, planning to become pregnant, or not using effective birth control.

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

Timeline for a Trial Participant

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. Dose escalation occurs over 8 to 16 weeks, followed by maintenance for up to 40 weeks.

40 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and hypoglycemic episodes.

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Placebo
• Semaglutide

Trial Overview

The study tests how well CagriSema, an experimental medication not yet available by prescription, lowers blood sugar and body weight compared to a placebo—a treatment with no active effect on the body.

How Is the Trial Designed?

Group I: CagriSema Dose 2 Active Control 2 Interventions

Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 16-week dose escalation period until target dose (dose 2) of CagriSema (cagrilintide and semaglutide) is achieved and maintained up to 24 weeks.

Group II: Cagrisema Dose 1 Active Control 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 32 weeks.

Group III: Placebo Dose 2 Placebo Group 1 Intervention

Participants will receive once-weekly s.c injection of placebo matched to Cagrisema (cagrilintide and semaglutide) dose 2 for 40 weeks.

Group IV: Placebo Dose 1 Placebo Group 1 Intervention

Participants will receive once-weekly s.c injection of placebo matched to Cagrisema (cagrilintide and semaglutide) dose 1 for 40 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 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, 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]

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]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

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 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]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively improve blood sugar control and promote weight loss, with a favorable safety profile similar to other GLP-1RAs, based on extensive phase 3 trials including cardiovascular outcome studies.

The most common side effects of semaglutide are mild-to-moderate gastrointestinal disturbances, and while there are concerns about pancreatic and thyroid cancer, no unexpected safety issues have been identified, making it a beneficial option for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. Smits, MM., Van Raalte, DH.[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]

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]

Citations

1.

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.

2.

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 ...

3.

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. ... We now provide the efficacy and safety results ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40544433/

Coadministered Cagrilintide and Semaglutide in Adults ...

The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with ...

5.

the-innovation.org

the-innovation.org/article/doi/10.59717/j.xinn-med.2025.100150

The next frontier in metabolic health: Cagrilintide-Semaglutide ...

Furthermore, the combination therapy led to significant improvements in BMI, waist circumference, blood pressure (systolic blood pressure reduction of 9.9 mmHg ...

6.

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.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05394519

NCT05394519 | A Research Study to See How Well ...

This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight.