CagriSema for Type 2 Diabetes

(REIMAGINE 5 Trial)

Recruiting at 162 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: Anti-obesity medications

Disqualifiers: Pregnancy, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 60 weeks

1023 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of certain diabetes medications like Metformin or SGLT2 inhibitors for at least 90 days before joining. If you are taking other diabetes or weight-loss medications, you would need to stop those 90 days before the trial.

What data supports the effectiveness of the drug CagriSema for Type 2 Diabetes?

Research shows that semaglutide, a component of CagriSema, is effective in improving blood sugar control in people with type 2 diabetes. Additionally, tirzepatide, another component, has been shown to significantly reduce blood sugar levels and body weight, making it more effective than semaglutide alone. ^{1 2 3 4 5}

Is CagriSema safe for humans?

CagriSema, also known as Tirzepatide, has been tested in clinical trials for type 2 diabetes and is generally considered safe, with common side effects including nausea, vomiting, diarrhea, and constipation, especially at higher doses. Cardiovascular safety has been evaluated, showing no increased risk of major cardiovascular events. ^{4 6 7 8 9}

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

CagriSema is unique because it combines semaglutide, a GLP-1 receptor agonist that helps lower blood sugar and reduce weight, with cagrilintide, an amylin analogue that enhances these effects. This combination aims to provide superior glucose control and weight loss compared to existing treatments. ^{1 4 7 10 11}

What is the purpose of this trial?

This study will look at how much CagriSema lowers blood sugar and body weight in people with type 2 diabetes. CagriSema is a new investigational medicine. Doctors cannot yet prescribe CagriSema. CagriSema will be compared to a medicine called tirzepatide. Doctors can prescribe tirzepatide in some countries. Participants will either receive CagriSema or tirzepatide. Which treatment the participant will receive is decided by chance. For each participant, the study will last for up to 1 year and 4 months.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for people with type 2 diabetes who are currently being treated with metformin, SGLT2 inhibitors, or both. Participants should not have any health conditions that would interfere with the study or make it unsafe for them.

Inclusion Criteria

I am either male or female.

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

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

Exclusion Criteria

I am not pregnant, breastfeeding, planning to become pregnant, or if of childbearing potential, I am using effective contraception.

I haven't taken any diabetes or weight loss drugs in the last 90 days, except for short-term insulin.

I do not have unstable diabetic eye problems verified by a recent eye exam.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-weekly subcutaneous injections of either CagriSema or tirzepatide, with a dose escalation period followed by maintenance for up to 60 weeks

60 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• CagriSema
• Tirzepatide

Trial Overview The study compares CagriSema (a new investigational medicine) and tirzepatide (an existing medication) to see which one better lowers blood sugar and body weight over a period of up to 1 year and 4 months. Treatment assignment is random.

Participant Groups

Group I: Tirzepatide Experimental Treatment 1 Intervention

Participants will receive once-weekly s.c injections of tirzepatide at escalating dose in a 4-week dose escalating period and maintained up to 56 weeks.

Group II: CagriSema Experimental Treatment 2 Interventions

Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 8-week dose escalation period until target dose of CagriSema is achieved and maintained for 52 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 study of 1748 adults with inadequately controlled type 2 diabetes, once-weekly semaglutide led to a greater reduction in HbA1c levels compared to thrice-daily insulin aspart over 52 weeks, indicating better glycemic control.

Semaglutide also resulted in significant weight loss (-4.1 kg) compared to insulin aspart (+2.8 kg), while both treatments had a similar low incidence of severe hypoglycemic episodes, suggesting semaglutide may be a safer and more effective option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. Kellerer, M., Kaltoft, MS., Lawson, J., et al.[2022]

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]

In a phase 3a trial involving 1089 participants, semaglutide significantly reduced HbA1c levels more than insulin glargine, achieving reductions of 1.21% and 1.64% for 0.5 mg and 1.0 mg doses, respectively, compared to 0.83% with insulin glargine.

Semaglutide also led to weight loss (3.47 kg and 5.17 kg for the two doses) while insulin glargine resulted in weight gain (1.15 kg), and semaglutide was associated with fewer hypoglycaemic episodes, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Aroda, VR., Bain, SC., Cariou, B., et al.[2022]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

In a study comparing tirzepatide and semaglutide in patients with type 2 diabetes, tirzepatide demonstrated superior efficacy in reducing HbA1c levels and body weight, indicating it may be a more effective treatment option.

The trial involved a significant number of participants and showed that tirzepatide not only improved glycemic control but also had a favorable safety profile, making it a promising alternative to existing diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide. Gandhi, GY.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

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 significantly reduced HbA1c levels by 1.0 to 1.5% and body weight by 2.2 to 5.0 kg in patients with type 2 diabetes, regardless of their background medications, indicating its broad efficacy across different treatment regimens.

The safety profile of oral semaglutide was consistent across various background medication subgroups, with no significant increase in adverse events, making it a suitable option for patients using other glucose-lowering agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Pratley, RE., Crowley, MJ., Gislum, M., et al.[2021]

Semaglutide, a GLP-1 receptor agonist, significantly reduces HbA1c levels by up to 1.38% and also helps in reducing body weight and systolic blood pressure, making it an effective treatment for type 2 diabetes.

While semaglutide shows a good safety profile with no increased rates of hypoglycemia, it is associated with higher incidences of gastrointestinal side effects like nausea and vomiting, and further monitoring is needed for potential risks of pancreatitis and diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Andreadis, P., Karagiannis, T., Malandris, K., et al.[2022]

Tirzepatide (15 mg) leads to a greater average weight loss of 17.8% compared to semaglutide (2.4 mg), which results in a 12.4% weight loss, making tirzepatide more effective for weight management in patients with type 2 diabetes.

In terms of cost-effectiveness, tirzepatide requires approximately $985 to achieve a 1% reduction in body weight, while semaglutide costs about $1845 for the same reduction, indicating that tirzepatide offers better value for money.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. Azuri, J., Hammerman, A., Aboalhasan, E., et al.[2023]

Long-acting GLP-1 analogues, such as semaglutide and tirzepatide, have shown significant efficacy in lowering blood glucose and body weight, making them promising treatments for type 2 diabetes and obesity.

The increasing demand for GLP-1R agonists like liraglutide and semaglutide has led to shortages, prompting a prioritization of their use in diabetes therapy over obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on peptide-based therapies for type 2 diabetes and obesity. Bailey, CJ., Flatt, PR., Conlon, JM.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. [2022]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. [2022]

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

In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. [2023]

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

Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. [2023]

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

An update on peptide-based therapies for type 2 diabetes and obesity. [2023]