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AMBITION 7: A Research Study Investigating How Well Zenagamtide Lowers Blood Sugar and Body Weight Compared to Insulin Glargine in People With Type 2 Diabetes and Increased Risk of Diseases That Affect the Heart and Blood Vessels Treated With 1-3 Other Diabetes Medications

NCT07797335 · Novo Nordisk A/S
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Official title
Efficacy and Safety of Zenagamtide s.c. Once Weekly Compared to Insulin Glargine s.c. Once Daily in Participants With Type 2 Diabetes and Increased Cardiovascular Risk Inadequately Controlled on 1-3 Oral Glucose-lowering Medications (AMBITION 7)
About this study
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.
Eligibility criteria
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.
Study design
Enrollment target: 1778 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2026-08-24
Estimated completion: 2028-09-20
Last updated: 2026-09-01
Interventions
Drug: ZenagamtideDrug: Insulin glargine U-100
Primary outcomes
  • Non-inferiority of zenagamtide versus insulin glargine: change in haemoglobin A1c (HbA1c) (From baseline (week 0) to week 52)
Sponsor
Novo Nordisk A/S · industry
Contacts & investigators
ContactNovo Nordisk · contact · clinicaltrials@novonordisk.com · (+1) 866-867-7178
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SIYODE S.A. de C.V. UnimedenNot Yet Recruiting
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Centro de Desarrollo Biomédico S.C.P.Not Yet Recruiting
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Medical Care and Research S. A de C.VNot Yet Recruiting
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Zana-Med Medical Group Sp. z o.o.Not Yet Recruiting
Lublin, Lublin Voivodeship, Poland
NZOZ Vita-Diabetica Malgorzata BuraczykNot Yet Recruiting
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Uniwersytecki Szpital Kliniczny w BialymstokuNot Yet Recruiting
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Osteo-Medic s.c. A. Racewicz, J. SupronikNot Yet Recruiting
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Kresmed Sp. z o. o.Not Yet Recruiting
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Zespol Opieki Zdrowotnej w BoleslawcuNot Yet Recruiting
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Diab Serwis Popenda Spółka JawnaNot Yet Recruiting
Chorzów, Poland
Gyncentrum Sp. z o. o.Not Yet Recruiting
Katowice, Poland
Centrum Medyczne MBB-MED Marta Blach-BurekNot Yet Recruiting
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Gabinet Lekarski Malgorzata Saryusz-WolskaNot Yet Recruiting
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Amicare Sp. z o.o. S.K.Not Yet Recruiting
Lodz, Poland
Velocity Nova Sp. z o.o.Not Yet Recruiting
Lublin, Poland
Etyka Osrodek Badan Klinicznych Tomasz Pesta S.K.A.Not Yet Recruiting
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Irmed Klimkiewicz Rudziewicz-Kowalska sp. j.Not Yet Recruiting
Piotrkow Trybunalski, Poland
Centrum Zdrowia Metabolicznego Paweł BogdańskiNot Yet Recruiting
Poznan, Poland
Maciej Wiza Gaja Poradnie LekarskieNot Yet Recruiting
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Velocity Nova Sp. z o.o.Not Yet Recruiting
Puławy, Poland
Centrum Medyczne Medyk Sp.zo.o. Sp.k.Not Yet Recruiting
Rzeszów, Poland
Medicover Integrated Clinical Services Sp. z o.o.Not Yet Recruiting
Torun, Poland
Szpital Czerniakowski Sp. z o.o.Not Yet Recruiting
Warsaw, Poland
PANSTWOWY INSTYTUT MEDYCZNY MSWiANot Yet Recruiting
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Regionalna Poradnia Diabetologiczna-Zytkiewicz-Jaruga, Stasinska Spolka Partnerska LekarzyNot Yet Recruiting
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Velocity Nova Sp. z o.o.Not Yet Recruiting
Zamość, Poland
Prywatna Praktyka Lekarska Anna ChudobaNot Yet Recruiting
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CHUAC_EndocrinologíaNot Yet Recruiting
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Hosp. Vall d'Hebrón_EndocrinologíaNot Yet Recruiting
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Clinic Barcelona_EndocrinologíaNot Yet Recruiting
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Hospital de Mostoles_EndocrinologíaNot Yet Recruiting
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H Virgen del Camino_Sanlúcar_Medicina InternaNot Yet Recruiting
Sanlúcar de Barrameda, Spain
CHUS_EndocrinologíaNot Yet Recruiting
Santiago de Compostela, Spain
Hospital General de Segovia_EndocrinologíaNot Yet Recruiting
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Hospital General de Valencia_EndocrinologíaNot Yet Recruiting
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Sakarya Egitim ve Arastirma Hastanesi-NefrolojiNot Yet Recruiting
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Ankara Bilkent Şehir Hastanesi-DahiliyeNot Yet Recruiting
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Gaziantep Üniversitesi Hastanesi- EndokrinolojiNot Yet Recruiting
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Ege Üniversitesi Tip Fakultesi Hastanesi - NefrolojiNot Yet Recruiting
Izmir, Turkey (Türkiye)
Erciyes Üniversitesi Hastanesi- KardiyolojiNot Yet Recruiting
Kayseri, Turkey (Türkiye)
Kocaeli Üniversitesi Araştıma ve Uygulama Hastanesi - NefrolojiNot Yet Recruiting
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Bursa Yüksek İhtisas Eğitim ve Araştırma Merkezi-EndokrinolojiNot Yet Recruiting
Nilüfer/Bursa, Turkey (Türkiye)
Eskişehir Şehir Hastanesi- KardiyolojiNot Yet Recruiting
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Sivas Cumhuriyet Üniversitesi Hastanesi -EndokrinolojiNot Yet Recruiting
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Dicle Üniversitesi Tıp Fakültesi Sağlık Ve Araştırma Hastanesi- NefrolojiNot Yet Recruiting
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North Coast Medical LtdNot Yet Recruiting
Newquay, Cornwall, United Kingdom
Yeovil HospitalNot Yet Recruiting
Yeovil, Somerset, United Kingdom
Clifton Medical CentreNot Yet Recruiting
Rotherham, South Yorkshire, United Kingdom
Southmead HospitalNot Yet Recruiting
Bristol, United Kingdom
University Hospital Coventry - WISDEM CentreNot Yet Recruiting
Coventry, United Kingdom
Hull Royal Infirmary - DiabetesNot Yet Recruiting
Hull, United Kingdom
Ipswich Hospital - DiabetesNot Yet Recruiting
Ipswich, United Kingdom
Altnagelvin Area HospitalNot Yet Recruiting
Londonderry, United Kingdom
Joint Clinical Research Facility - SwanseaNot Yet Recruiting
Swansea, United Kingdom
Egremont Medical CentreNot Yet Recruiting
Wallasey, United Kingdom
AMBITION 7: A Research Study Investigating How Well Zenagamtide Lowers Blood Sugar and Body Weight Compared to Insulin Glargine in People With Type 2 Diabetes and Increased Risk of Diseases That Affect the Heart and Blood Vessels Treated With 1-3 Other Diabetes Medications · TrialPath