CagriSema for Chronic Kidney Disease and Type 2 Diabetes in Obesity

No longer recruiting at 245 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Must be taking: Ace inhibitors, Arbs

Must not be taking: Glp-1ra, Amylin analogues

Disqualifiers: Pregnancy, Hereditary kidney diseases, Dialysis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new medicine, CagriSema, can reduce kidney damage in individuals with chronic kidney disease (CKD), type 2 diabetes (T2D), and who are overweight. The study compares CagriSema (a combination of semaglutide and cagrilintide) to semaglutide, cagrilintide, and a placebo (a "dummy" treatment with no active medicine). Participants will be randomly assigned to one of these treatments without knowing which one they receive. Suitable candidates for this trial have type 2 diabetes, are overweight, and have been managing kidney issues. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of an ACE inhibitor or ARB for at least 30 days before screening. You cannot have used certain diabetes medications like GLP-1 receptor agonists within 60 days before screening.

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

Research has shown that CagriSema, a combination of semaglutide and cagrilintide, has been safe in past studies. One study on people with type 2 diabetes found that this combination was generally well-tolerated, with most side effects being mild, such as nausea or slight discomfort, which are common with weight-loss treatments.

Semaglutide alone has been used for type 2 diabetes and obesity and is considered safe. Studies have shown it helps with kidney health in people with type 2 diabetes and chronic kidney disease. Many people did not experience serious side effects, and the most common ones were minor.

Cagrilintide has also been tested for weight loss and shows promise in treating obesity. Most side effects are manageable and typical for weight-loss drugs.

These treatments are being studied in a trial for people with chronic kidney disease, type 2 diabetes, and obesity. The current phase of the trial suggests there is already some evidence that these treatments are safe, but more data is needed to confirm this fully. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CagriSema because it combines two active ingredients, cagrilintide and semaglutide, which could offer a new way to tackle chronic kidney disease and type 2 diabetes in people with obesity. Unlike existing treatments that typically focus on controlling blood sugar alone, CagriSema targets both appetite suppression and glucose regulation. Cagrilintide is an amylin analogue that helps reduce hunger, while semaglutide is a GLP-1 receptor agonist that improves insulin sensitivity. This dual approach not only aims to enhance blood sugar control but also supports weight management, addressing two critical aspects of managing these conditions effectively.

What evidence suggests that this trial's treatments could be effective for chronic kidney disease and type 2 diabetes in obesity?

This trial will compare the effects of different treatments on weight loss and kidney health in people with type 2 diabetes and obesity. Research has shown that CagriSema, a combination of cagrilintide and semaglutide, may aid weight loss in individuals with obesity and type 2 diabetes. In studies, 60% of participants lost 20% or more of their body weight with this combination, proving more effective than many other treatments. Participants in this trial may receive CagriSema, semaglutide alone, or cagrilintide alone. Semaglutide alone has reduced kidney damage and lowered the risk of serious kidney problems in people with type 2 diabetes and chronic kidney disease. Cagrilintide also shows promise as a weight loss treatment, making it a strong option for managing obesity. These findings suggest that CagriSema could improve both weight loss and kidney health in people with type 2 diabetes and obesity. ^{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?

Adults over 18 with chronic kidney disease, type 2 diabetes, and a BMI of at least 27 can join this study. They must have some kidney function left (eGFR ≥15 to <90), not be on dialysis, and have been treated with specific blood pressure meds for at least a month. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

You have a high level of albumin in your urine, as tested by the central laboratory at the start of the study.

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

My BMI is 27 or higher.

Exclusion Criteria

I haven't used GLP-1 receptor agonists or amylin analogues in the last 60 days.

I have a genetic or autoimmune kidney disease, like polycystic kidney disease or glomerulonephritis.

I have been on dialysis in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants undergo a dose escalation period to reach the target dose of study medication

16 weeks

Maintenance Treatment

Participants receive the assigned study medication or placebo once weekly

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• CagriSema
• Placebo
• Semaglutide

Trial Overview

The trial is testing CagriSema against Semaglutide, Cagrilintide, and placebo in reducing kidney damage for people with CKD and T2D who are overweight. Treatments are assigned randomly like flipping a coin, and neither participants nor doctors know which one they get.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 2 Interventions

Participants will receive semaglutide and placebo matched to cagrilintide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group II: Cagrilintide Experimental Treatment 2 Interventions

Participants will receive cagrilintide and placebo matching to semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group III: CagriSema Experimental Treatment 2 Interventions

Participants will receive cagrilintide and semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously once weekly for 26 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

Oral semaglutide significantly improved glycaemic control and reduced body weight in patients with type 2 diabetes and moderate renal impairment, showing a mean decrease in HbA1c of -1.0 percentage points compared to -0.2 with placebo over 26 weeks.

While more patients experienced adverse events with oral semaglutide (74%) compared to placebo (65%), the safety profile was consistent with other GLP-1 receptor agonists, indicating it may be a viable treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Mosenzon, O., Blicher, TM., Rosenlund, S., et al.[2020]

In a study involving 486 type 2 diabetes patients, semaglutide was found to be effective in improving glycemic control and achieving weight loss, with no significant differences in efficacy between patients with chronic kidney disease (CKD) and those without.

The treatment was safe for all patients, and CKD severity did not notably affect the treatment response, suggesting that semaglutide can be effectively used in managing type 2 diabetes in patients with varying levels of kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. García de Lucas, MD., Caballero, I., Fernández-García, JC., et al.[2023]

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors provide cardiovascular and renal protection for patients with diabetic kidney disease, but there is still a high residual risk and limited effectiveness in moderate to severe chronic kidney disease (CKD).

Oral semaglutide, a GLP-1 receptor agonist, offers a promising alternative with potent antihyperglycemic effects, low risk of hypoglycemia, and cardiovascular and renal benefits, potentially improving early treatment options for patients with type 2 diabetes and diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. Cases, A.[2023]

Subcutaneous semaglutide (Ozempic®), a GLP-1 receptor agonist, has shown significant efficacy in improving glycemic control and reducing HbA1c, albuminuria, and blood pressure in patients with advanced diabetic kidney disease (DKD) during a 6-month follow-up study involving patients on maintenance hemodialysis.

The treatment not only aids in weight loss and appetite suppression but also helps preserve residual kidney function, potentially improving patient outcomes and facilitating their inclusion on kidney transplant waiting lists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. De la Flor, JC., Lorenzo, JD., Marschall, A., et al.[2022]

In the STEP 2 trial involving 1,205 participants, semaglutide (both 1.0 mg and 2.4 mg) significantly improved kidney function as measured by urine albumin-to-creatinine ratio (UACR), with reductions of -14.8% and -20.6% respectively, compared to an increase of +18.3% in the placebo group.

Across pooled data from STEP 1-3, semaglutide did not affect estimated glomerular filtration rate (eGFR) decline in participants with normal kidney function, indicating its safety in terms of kidney function preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Heerspink, HJL., Apperloo, E., Davies, M., et al.[2023]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[2023]

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 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]

Citations

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hcplive.com

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ADA 2025: CagriSema Demonstrates Dual Benefit in ...

CagriSema was associated with weight reductions in the highest range of existing weight loss interventions.

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sup.jclinque.com

sup.jclinque.com/uploads/manuscript_2_ef74582707.pdf

Comparative Efficacy and Safety of Semaglutide, Cagrilintide, ...

A meta-analytic review of the safety and efficacy of. 408 semaglutide in type 2 diabetes mellitus and chronic kidney disease patients. Ann Med Surg (Lond) ...

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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.

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appliedclinicaltrialsonline.com

appliedclinicaltrialsonline.com/view/cagrilintide-semaglutide-weight-loss

REDEFINE 1 Trial Finds Cagrilintide–Semaglutide Combo ...

Once-weekly cagrilintide–semaglutide combination therapy produced unprecedented weight reductions in adults with overweight or obesity, with 60% achieving ≥20% ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06221969

NCT06221969 | A Research Study to See How Much ...

This study will look at how well CagriSema helps people with type 2 diabetes lower their blood sugar and body weight. CagriSema is a new investigational ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0140673623011637

Articles Efficacy and safety of co-administered once-weekly ...

This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes. Methods. This ...

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acc.org

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Cagrilintide-Semaglutide in Type 2 Diabetes - CagriSema

This study medication had an acceptable safety profile. This exploratory trial supports the further investigation of this combination agent in ...