A Research Study to Compare Blood Levels of Cagrilintide and Semaglutide After Combined Versus Separate Injections in People With Overweight or Obesity

Recruiting at 2 trial locations

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Disqualifiers: Pregnancy, Amylin analogue, others

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

Compensation: Varies

Number of Visits: 28

Duration: 22 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug CagriSema?

Research shows that combining semaglutide with cagrilintide (CagriSema) can help with weight loss in people with type 2 diabetes. Semaglutide alone has been effective in controlling blood sugar levels without causing weight gain or other side effects. ^{1 2 3 4 5}

What makes the drug Cagrilintide and Semaglutide unique compared to other treatments?

Cagrilintide and Semaglutide (CagriSema) is unique because it combines two components: semaglutide, a GLP-1 receptor agonist that helps control blood sugar levels, and cagrilintide, which may enhance weight loss. This combination aims to improve glycemic control and promote weight loss more effectively than using semaglutide alone. ^{1 6 7 8 9}

What is the purpose of this trial?

This trial is testing two weight-loss drugs, cagrilintide and semaglutide, given either as one combined shot or as two separate shots. The study targets overweight or obese individuals to find the best way to administer these medications. These drugs work by reducing appetite and controlling blood sugar levels, which helps with weight loss. Cagrilintide is a long-acting drug currently being tested for obesity, and semaglutide has shown significant weight loss effects.

Research Team

Clinical Transparency (dept. 1452)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

Inclusion Criteria

Male or female of non-childbearing potential (NCBP)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cagrilintide and semaglutide as separate injections for 14 weeks, followed by either combined or separate injections for 8 weeks

22 weeks

28 visits (in-person), 4 extended stays

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 days

Treatment Details

Interventions

• Cagrilintide
• Semaglutide

Participant Groups

Group I: Part B: Cagrilintide and semaglutide combined in DV3384 device Experimental Treatment 1 Intervention

Participants will receive a single injection of Cagrilintide 0.25 mg/semaglutide 0.25 mg using the DV3384 manual syringe followed by a 28 days follow-up period.

Group II: Part A: Cagrilintide and semaglutide in separate syringes Experimental Treatment 2 Interventions

Participants will up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks treatment with cagrilintide and semaglutide administered as separate injections. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination). Followed by a 38 days follow-up period.

Group III: Part A: Cagrilintide and semaglutide combined in DV3384 device Experimental Treatment 1 Intervention

Participants will be up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks of treatment with cagrilintide and semaglutide administered using the DV3384 manual syringe. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination. Followed by a 38 days follow-up period.

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 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, 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 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 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, 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 52-week study involving 731 patients with type 2 diabetes, oral semaglutide significantly reduced HbA1c levels and body weight compared to placebo, demonstrating its efficacy when added to insulin with or without metformin.

The most common side effect of oral semaglutide was nausea, which was mostly mild to moderate, indicating a safety profile similar to other glucagon-like peptide 1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Zinman, B., Aroda, VR., Buse, JB., et al.[2022]

Oral semaglutide, a GLP-1 analogue, was found to be safe and well-tolerated in two clinical trials involving 135 healthy males and 23 males with type 2 diabetes, with most adverse events being mild and primarily gastrointestinal.

The pharmacokinetics showed that semaglutide exposure increased with higher doses and was consistent across healthy individuals and those with type 2 diabetes, supporting its suitability for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. Granhall, C., Donsmark, M., Blicher, TM., et al.[2020]

References

1. England 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. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis. [2022]

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

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

4. 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]

5. England 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. [2023]

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

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. [2018]

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

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. [2020]