Type 2 Diabetes, Cardiovascular Risk
Conditions
Brief summary
This study is being conducted to find out how well zenagamtide works and how safe it is compared to insulin glargine in participants with type 2 diabetes who are at higher risk of heart and blood vessel problems and are already taking 1 to 3 diabetes medications. There are 2 study treatments in this study taken as injections under the skin once a week. Participants will either get zenagamtide, (the treatment being tested) or insulin glargine (a comparator) and which treatment participants get is decided by chance.
Interventions
DRUGZenagamtide
Zenagamtide will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm (administration to the same body part throughout the study).
DRUGInsulin glargine U-100
Insulin glargine U-100 will be administered subcutaneously using SoloSTAR pen-injector to one of the body parts: thigh, abdomen or upper arm (rotation of the injection site within body parts).
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. * Male or female (sex assigned at birth, inclusive of all gender identities). * Age 45 years or above at the time of signing the informed consent. * Diagnosed with type 2 diabetes (T2D) greater than or equal to (≥) 180 days before screening. * Treatment with 1-3 marketed oral glucose-lowering medications (metformin, glinide, thiazolidinedione, sodium-glucose cotransporter-2 inhibitors (SGLT2i), α-glucosidase inhibitors (AGI), or sulfonylureas (SU) as a single agent or in combination) according to local label. Treatment with oral glucose-lowering medications must be stable (same drug(s), stable daily dose(s)) before screening. * Have HbA1c as determined by central laboratory at screening, if background glucose-lowering medications does not include a SU, or if background glucose-lowering medications includes a SU. * Increased risk of cardiovascular events as evidenced by at least one of the following (a-e): * Prior myocardial infarction (MI) * Documented coronary artery disease defined by at least one of the following: -≥ 50% stenosis of coronary artery on angiography or other imaging modality. * Ischaemia documented by stress test with any imaging modality. * Prior unstable angina with electrocardiogram (ECG) changes. * Prior coronary artery bypass graft or prior percutaneous coronary intervention. * Prior stroke (ischemic or haemorrhagic stroke). * History of chronic kidney disease based on medical records or as judged by the investigator as determined by central laboratory at screening. * Symptomatic peripheral arterial disease (PAD) defined as at least one of the following: * Intermittent claudication with an ankle-brachial index (ABI) \< 0.85 at rest. * Intermittent claudication with a ≥ 50% stenosis in a lower extremity peripheral artery documented by X-ray angiography, magnetic resonance (MR) angiography, computer tomography (CT) angiography or Doppler ultrasound. * Prior revascularisation procedure of a lower extremity peripheral artery. * Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis)
Exclusion criteria
* Myocardial infarction, stroke, transient ischaemic attack or hospitalisation for unstable angina pectoris within 60 days before screening. * Planned coronary, carotid or peripheral artery revascularisation. * Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening. Diabetes- or weight related: * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria before screening. However, insulin treatment for gestational diabetes is allowed as well as short term insulin treatment for a maximum of 14 consecutive days. * Treatment with glucagon-like-peptide-1 (GLP-1) receptor agonists (RA), dual GLP1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment), dipeptidyl peptidase 4 (DPP-4) inhibitors or amylin analogues before screening. * Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) within 180 days before screening or are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination. * Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question. * Any episodes of diabetic ketoacidosis before screening. * Uncontrolled thyroid disease as per investigator's discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority of zenagamtide versus insulin glargine: change in haemoglobin A1c (HbA1c) | From baseline (week 0) to week 52 | Measured as percentage (%)-points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of a 4-point major adverse cardiovascular events (MACE) endpoint consisting of: Cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for unstable angina | From baseline (week 0) to 104 weeks or more | Measured as days |
| Relative change in body weight | From baseline (week 0) to week 52 | Measured as percentage (%) change |
| Superiority of zenagamtide versus insulin: Change in HbA1c | From baseline (week 0) to week 52 | Measured as %-points |
| Time to first occurrence of a 3-point MACE endpoint consisting of: CV death, non-fatal myocardial infarction and non-fatal stroke | From baseline (week 0) to 104 weeks or more | Measured as Days |
| Change in waist circumference | From baseline (week 0) to week 52 | Measured as centimeters |
| Change in systolic blood pressure | From baseline (week 0) to week 52 | Measured as millimeters of mercury (mmHg) |
| Change in high-sensitivity C-reactive protein (hsCRP) | From baseline (week 0) to week 52 | Measured as ratio to baseline |
| Change in Triglycerides | From baseline (week 0) to week 52 | Measured as ratio to baseline |
| Change in Non-high-density lipoprotein (non-HDL) cholesterol | From baseline (week 0) to week 52 | Measured as ratio to baseline |
Countries
Argentina, Brazil, Bulgaria, Canada, China, Czechia, Germany, Greece, India, Italy, Mexico, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTNovo Nordisk
Outcome results
None listed