CagriSema for Type 2 Diabetes

(REIMAGINE 3 Trial)

No longer recruiting at 71 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Basal insulin, Metformin

Must not be taking: Other diabetes, Obesity drugs

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, a combination of Semaglutide and Cagrilintide, to determine if it can help people with type 2 diabetes lower their blood sugar and lose weight. Participants will receive either CagriSema or a placebo (a "dummy" medicine without active ingredients) alongside their usual diabetes medication. This study may suit individuals with type 2 diabetes who have maintained a stable insulin routine and possibly metformin for the last few months. By joining, participants will help researchers assess how well CagriSema works compared to a placebo. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

You can continue taking your current diabetes medications, like once-daily insulin and metformin, during the trial. However, if you are on other diabetes or obesity medications, you may need to stop those before joining.

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 people with type 2 diabetes. In earlier studies, participants experienced significant weight loss without serious side effects. One study found that CagriSema led to more weight loss than using either semaglutide or cagrilintide alone, and it was well-tolerated by participants.

Some mild side effects, such as stomach issues, were reported, but these were uncommon and did not lead to discontinuation of the treatment. These findings suggest that CagriSema is safe for most people, but discussing any concerns with a healthcare provider is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CagriSema for Type 2 Diabetes because it combines two active ingredients, cagrilintide and semaglutide, offering potential benefits over standard treatments like metformin, sulfonylureas, and insulin. Unlike these standard treatments, CagriSema incorporates cagrilintide, a novel amylin analog, which may help regulate appetite and improve blood sugar control. Additionally, semaglutide is a GLP-1 receptor agonist known for its effectiveness in lowering blood sugar and promoting weight loss. This combination aims to address multiple aspects of diabetes management, potentially providing improved outcomes for patients.

What evidence suggests that CagriSema might be an effective treatment for type 2 diabetes?

Research has shown that CagriSema, a combination of cagrilintide and semaglutide, can significantly aid people with type 2 diabetes in managing their weight and blood sugar. In earlier studies, participants using CagriSema lost up to 15.7% of their body weight, marking a significant reduction. Additionally, about 74% of participants achieved a blood sugar level of 6.5% or lower, a key target for diabetes management. In this trial, participants will receive either CagriSema at varying doses or a placebo. These findings suggest that CagriSema not only aids in weight loss but also enhances blood sugar control, making it a promising treatment for 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 are already taking once-daily basal insulin, with or without metformin. Participants should not be on any other diabetic medications and must have a stable dose of insulin for at least 90 days prior to the start of the study.

Inclusion Criteria

I am either male or female.

Glycated haemoglobin (HbA1c) 7.0-10.5 percent (53-91 millimoles per mole [mmol/mol]) (both inclusive) as determined by central laboratory at screening

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

Exclusion Criteria

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

My kidney function is severely impaired, with an eGFR below 30.

I haven't taken diabetes or obesity drugs not listed in the criteria in the last 90 days.

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 for up to 40 weeks, with dose escalation periods for active comparators

40 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Placebo
• Semaglutide

Trial Overview

The study tests CagriSema, a new medication, against a placebo (a dummy medicine) in lowering blood sugar and body weight in type 2 diabetics. Patients will receive either CagriSema or placebo randomly while continuing their current diabetes treatment.

How Is the Trial Designed?

Group I: 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 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 1 Placebo Group 1 Intervention

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

Group IV: 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 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

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 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 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]

In a 12-week trial involving 75 adults with type 2 diabetes, semaglutide significantly improved both first- and second-phase insulin secretion, indicating enhanced beta cell function.

Semaglutide also led to better glycaemic control, with reduced fasting and postprandial glucose levels, and was well tolerated by participants, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Kapitza, C., Dahl, K., Jacobsen, JB., 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]

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]

In a study involving 56 subjects with varying degrees of renal impairment, semaglutide exposure was found to be similar in those with mild to moderate renal impairment and end-stage renal disease compared to those with normal kidney function, suggesting it is safe for use in these populations.

The drug was well-tolerated overall, with no significant safety concerns or serious adverse events reported, indicating that dose adjustments for semaglutide may not be necessary for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. Marbury, TC., Flint, A., Jacobsen, JB., et al.[2018]

Oral semaglutide significantly reduces HbA1c levels and body weight in patients with type 2 diabetes, showing greater efficacy than placebo and other antidiabetic agents in a review of 11 randomized controlled trials involving 9890 patients.

While oral semaglutide is effective in managing blood glucose and weight, it is associated with increased gastrointestinal side effects like nausea and vomiting, although it has a favorable safety profile regarding severe hypoglycemia and cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. Avgerinos, I., Michailidis, T., Liakos, A., et al.[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]

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Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 ...

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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 ...

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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.

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In people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM ...

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Importantly, findings also showed that 74% of patients with T2D receiving CagriSema achieved a glycated hemoglobin level ≤6.5% vs. 15.9% with ...

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Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated.

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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.