AMAZE 8: A Research Study Investigating How Well the Medicine NNC0487-0111 Compared to Semaglutide Helps People With Excess Body Weight and Type 2 Diabetes Lose Weight (AMAZE 8)

Efficacy and Safety of NNC0487-0111 s.c. Once-weekly Compared to Semaglutide s.c. Once-weekly in Participants With Overweight or Obesity, and Type 2 Diabetes (AMAZE 8)

The purpose of this clinical study is to find out if NNC0487-0111 is safe and effective for treating people who have excess body weight and type 2 diabetes. Participant will receive 2 injections every week: an active medicine and a placebo, both taken as injections under the skin once a week. The placebo is a treatment with no active medicine in it and will be given to all participants. In addition to placebo, participants will receive either of the active medicine NNC0487-0111 (the treatment being tested) or Semaglutide (an approved and commonly prescribed treatment used as comparator). Which treatment participants get is decided by chance.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Diabetes Mellitus, Type 2; Overweight
• Intervention / Treatment: Drug: NNC0487-0111; Drug: Placebo (matched to semaglutide); Drug: Semaglutide; Drug: Placebo (matched to NNC0487-0111)

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Argentina
  • Córdoba, Argentina, X5006IKK
    • Centro Medico Privado San Vicente Diabetes
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1056ABI
      • Centro de Investigaciones Metabólicas
    • Lanús Este, Buenos Aires, Argentina, B1824KAJ
      • Centro Médico CIMEL
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
      • Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.
  • São Paulo
    • Campinas, São Paulo, Brazil, 13092-133
      • i9 Pesquisas Clínicas
    • São Paulo, São Paulo, Brazil, 01228-000
      • CPQuali Pesquisa Clinica Ltda
    • São Paulo, São Paulo, Brazil, 01236-030
      • BR Trials - Ensaios Clínicos e Consultoria Ltda.
• Bulgaria
  • Gotse Delchev, Bulgaria, 2900
    • Dr. Tatyana Metalova - AIPSMCE EOOD
  • Kozloduy, Bulgaria, 3320
    • Medical centre Zdrave 1 OOD
  • Pazardzhik, Bulgaria, 4400
    • UMHAT Pulmed OOD - Pazardzhik, Department of Internal Diseases
  • Pleven, Bulgaria, 5801
    • DCC I- Pleven EOOD Endocrinology
  • Pleven, Bulgaria, 5800
    • MHAT Heart and Brain EAD - Pleven, Endocrinology and Metabolic Diseases
  • Sofia, Bulgaria, 1606
    • Medical Institute of Ministry of interior
  • Sofia, Bulgaria, 1233
    • MHAT Knyaginya Klementina - Sofia EAD
  • Sofia, Bulgaria, 1431
    • USHATE Akad. Ivan Penchev EAD, Second Clinic of Endocrinology
  • Sofia, Bulgaria, 1404
    • MHAT Sveta Sofia EOOD, Department of Endocrinology and Metabolic diseases
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic UMHAT Tokuda EAD, Endocrinology
  • Varna, Bulgaria, 9000
    • Medical Centre - Clinic Nova EOOD
• Croatia
  • Grad Zagreb, Croatia, 10000
    • Poliklinika Medikol Zagreb
  • Karlovac, Croatia, 47000
    • Opća bolnica Karlovac
  • Krapinske Toplice, Croatia, 49217
    • Specijalna Bolnica za medicinsku rehabilitaciju Krapinske Toplice_Endocrinology
  • Osijek, Croatia, 31000
    • Poliklinika SLAVONIJA OSIJEK
  • Rijeka, Croatia, 51 000
    • Clinical Hospital Centre Rijeka_Endocrinology
  • Slavonski Brod, Croatia, 35 000
    • General Hospital Dr. Josip Bencevic_Diabetic department
  • Varaždin, Croatia, 42 000
    • Opca bolnica Varazdin_Endocrinology
  • Zagreb, Croatia, 10000
    • Poliklinika Solmed
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW - Bad Oeynhausen
  • Elsterwerda, Germany, 04910
    • Zentrum fuer Klinische Studien Suedbrandenburg GmbH
  • Essen, Germany, 45355
    • Praxis am Markt Dr. Becker
  • Fulda, Germany, 36037
    • MVZ im Altstadt-Carree Fulda GmbH - Zentrum für klinische Studien
  • Hamburg, Germany, 21109
    • Diabetes-Zentrum-Wilhelmsburg GbR
  • Lingen, Germany, 49808
    • Diabetologische Gemeinschaftspraxis Dr. Staudenmeyer und Dr. Schiwietz
  • Magdeburg, Germany, 39120
    • SMO.MD GmbH - Zentrum für klinische Studien
  • Osnabrück, Germany, 49080
    • Institut für Diabetesforschung Osnabrück
  • Pohlheim, Germany, 35415
    • ceda - Centrum für Diabetologie und Allgemeinmedizin Pohlheim
  • Witten, Germany, 58455
    • Forschungszentrum Ruhr KliFoCenter GmbH, Kahrmann
• Hungary
  • Gyula, Hungary, 5700
    • Békés Vármegyei Központi Kórház
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem
  • Komárom-Esztergom
    • Komárom, Komárom-Esztergom, Hungary, 2900
      • Komaromi Selye Janos Korhaz
  • Pest County
    • Budapest, Pest County, Hungary, 1036
      • Óbudai Egészségügyi Centrum
  • Szabolcs-Szatmar Varmegye
    • Nyíregyháza, Szabolcs-Szatmar Varmegye, Hungary, 4405
      • Borbánya Praxis E.Ü. Kft.
• India
  • Aligarh, India, 202002
    • Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N Medical College, Aligarh Muslim University
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences (AIIMS)
  • Thriruvananthapuram, India, 695 032
    • Jothydev's Diabetes & Research Center
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Endolife Specialty Hospitals
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital Pvt. Ltd.
    • Vadodara, Gujarat, India, 390001
      • SSG Hospital, Baroda
  • Karnataka
    • Bangalore, Karnataka, India, 560010
      • Diacon Hospital Private Limited
    • Bengaluru, Karnataka, India, 560066
      • Lifecare Hospital and Research Centre
  • Kerala
    • Kochi, Kerala, India, 682041
      • Amrita Institute Of Medical Sciences & Research Centre
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • TOTALL Diabetes Hormone Institute
  • Maharashtra
    • Mumbai, Maharashtra, India, 400058
      • BSES MG hospital
    • Nagpur, Maharashtra, India, 441110
      • Shalini Tai Meghe Hospital and Research Center
    • Pune, Maharashtra, India, 411021
      • Chellaram Diabetes Institute
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • SMS Medical College & Hospital
    • Jaipur, Rajasthan, India, 302006
      • Diabetes, Thyroid and Endocrine Centre
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625 020
      • Arthur Asirvatham hospital,
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Nizam's Institute of Medical Sciences
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • IPGME&R and SSKM Hospital
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Diseño y Planeacion en Investigacion Medica S.C.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64020
      • Alliance CEINV Salud S.A. de C.V.
  • Tamaulipas
    • Ciudad Madero, Tamaulipas, Mexico, 89440
      • Centro de Estudios de Investigación Metabólicos y Cardio
• Poland
  • Bialystok, Poland, 15-435
    • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
  • Bialystok, Poland, 15-879
    • NZOZ Vita-Diabetica Malgorzata Buraczyk
  • Elblag, Poland, 82-300
    • Centrum Kliniczno-Badawcze J.Brzezicki B.Gornikiewicz-Brzezicka Lekarze sp.p.
  • Gorzów Wielkopolski, Poland, 66-400
    • Specjalistyczny Gabinet Diabetologiczny Radoslaw Rumianowski
  • Kalwaria Zebrzydowska, Poland, 34-130
    • SP ZOZ w Kalwarii Zebrzydowskiej
  • Krakow, Poland, 30-105
    • Linden sp. z o.o. sp. k.
  • Krakow, Poland, 31-559
    • Diamond Clinic sp zoo
  • Legnica, Poland, 59-220
    • Beata Miklaszewicz & Dariusz Dabrowski "CARDIAMED" s.j.
  • Leszno, Poland, 64-100
    • Serce Sp. z o.o.
  • Lodz, Poland, 90-132
    • Gabinet Lekarski Malgorzata Saryusz-Wolska
  • Lodz, Poland, 90-338
    • Centrum Terapii Wspolczesnej - J.M. Jasnorzewska S.K.A.
  • Ruda Śląska, Poland, 41-709
    • Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Specjalistyczna A Wittek H Rudzki Sp. j.
  • Siedlce, Poland, 08-110
    • Lukmed 2 Sp. z o.o.
  • Warsaw, Poland, 00-739
    • Szpital Czerniakowski Sp. z o.o.
  • Zabrze, Poland, 41-800
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Szyszko
  • Żyrardów, Poland, 96-300
    • Prywatna Praktyka Lekarska Anna Chudoba
  • Lesser Poland Voivodeship
    • Lublin, Lesser Poland Voivodeship, Poland, 20-064
      • Gabinety Medyczne MATUSZEK Beata Matyjaszek-Matuszek Prywatna Praktyka Specjalistyczna
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-718
      • Ekamed Sp. z o.o.
  • Mazovian Voivodeship
    • Grudziądz, Mazovian Voivodeship, Poland, 86-300
      • Przychodnie Grudziadz Sp. z o. o.
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-404
      • Legeartis Poradnie Specjalistyczne Sp. z o.o.
• Portugal
  • Alcabideche, Portugal, 2755-009
    • Hospital de Cascais
  • Almada, Portugal, 2805-267
    • ULS Almada-Seixal E.P.E. - Hospital Garcia de Orta
  • Braga, Portugal, 4710-243
    • ULS De Braga, E.P.E. - Hospital de Braga
  • Lisbon, Portugal, 1250-189
    • APDP - Associação Protectora dos Diabéticos de Portugal
  • Lisbon, Portugal, 1649-020
    • Hosp. das Forças Armadas_ Endocrinologia
  • Porto, Portugal, 4200-319
    • ULS De São João, E.P.E. - Hospital de São João
  • Senhora Da Hora, Matosinhos, Portugal, 4464-513
    • ULS De Matosinhos E.P.E.- Hospital Pedro Hispano
  • Vila Nova de Gaia, Portugal, 4400-346
    • Hospital da Luz Arrabida, S.A.
• Romania
  • Bacau, Romania, 600154
    • CMI Dr. Pletea Noemi SRL
  • Bucharest, Romania, 013764
    • SC Nutrilife SRL
  • Bucharest, Romania, 050913
    • Diabet Med SRL
  • Oradea, Romania, 410001
    • Medical Practice SRL
  • Satu Mare, Romania, 440055
    • Spital Judetean de Urgenta Satu Mare
  • Timișoara, Romania, 300288
    • Cabinet Medical Dr Geru SRL
  • București
    • Bucharest, București, Romania, 020475
      • Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila
  • Mureș County
    • Reghin, Mureș County, Romania, 545300
      • Poli Cardinal Med Srl
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital_Endocrinology
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital_Diabetes and Endocrinology
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
• Turkey (Türkiye)
  • Adana /yüreği̇r, Turkey (Türkiye), 01240
    • Başkent Üniversitesi Adana-Endokrinoloji
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Şehir Hastanesi-Dahiliye
  • Battalgazi / Malatya, Turkey (Türkiye), 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Hastanesi- Endokrinoloji
  • Istanbul, Turkey (Türkiye), 34722
    • Göztepe Prof. Dr.Süleyman Yalçın Şehir Hastanesi- Dahiliye
  • Pendik/istanbul, Turkey (Türkiye), 34899
    • Marmara Üniversitesi Pendik EAH- Endokrinoloji
  • Sivas, Turkey (Türkiye), 58140
    • Sivas Cumhuriyet Üniversitesi Hastanesi -Endokrinoloji
  • Yüreğir/Adana, Turkey (Türkiye), 1370
    • Adana Şehir Eğitim ve Araştırma Hastanesi-Endokrinoloji
• United States
  • Florida
    • Hollywood, Florida, United States, 33024
      • Encore Medical Research LLC
    • Orange City, Florida, United States, 32763
      • Optimal Research Sites
    • Weston, Florida, United States, 33331
      • Encore Medical Research of Weston
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Endo And Metab Cons
  • Michigan
    • Troy, Michigan, United States, 48098-6368
      • Arcturus Healthcare, PLC.
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clin Res, Dallas
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Virginia
    • Winchester, Virginia, United States, 22601-3834
      • Selma Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female (sex at birth).
• Age 18 years or above at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening.
• Haemoglobin A1c (HbA1c) 7-10 percentage (%) (53-86 millimole per mole [mmol/mol]) (both inclusive) as measured by the central laboratory at screening.
• Treatment with lifestyle intervention, and/or 0-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose cotransporter 2 inhibitor (SGLT2i), thiazolidinediones, or sulfonylureas (SU) as a single agent or in combination) according to local label. Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and dosing frequency) before screening.

Key Exclusion Criteria:

• Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 30 milliliter (mL)/ minute (min)/1.73 meter squared (m^2) (2021 Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula), at 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 within 90 days before screening or in the period between screening and randomization. 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 8.
• Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.
• Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists (RA), dual GLP-1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment), or amylin analogues before screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNC0487-0111; Participants will receive NNC0487-0111 and placebo matched to semaglutide subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: NNC0487-0111; NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.; Drug: Placebo (matched to semaglutide); Placebo matched to semaglutide will be administered subcutaneously using pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.
Active Comparator: Semaglutide; Participants will receive semaglutide and placebo matched to NNC0487-0111 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: Semaglutide; Semaglutide will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.; Drug: Placebo (matched to NNC0487-0111); Placebo matched to NNC0487-0111 will be administered subcutaneously using pre- filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in body weight	Measured as percentage of body weight.	From baseline (week 0) to week 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in diastolic blood pressure (DBP)	Measured as mmHg.	From baseline (week 0) to week 84
Change in waist circumference	Measured as centimeter (cm).	From baseline (week 0) to week 84
Change in systolic blood pressure (SBP)	Measured as millimeter of mercury (mmHg).	From baseline (week 0) to week 84
Change in body weight	Measured as kilograms (kg).	From baseline (week 0) to week 84 and week 104
Change in body mass index (BMI)	Measured as kilograms per meter squared (kg/m^2).	From baseline (week 0) to week 84 and week 104
Number of participants with achievement of in haemoglobin A1c (HbA1c) < 7.0 percent (%) (yes/no)	Measured as count of participants.	From baseline (week 0) to week 84
Number of participants with achievement of HbA1c ≤ 6.5% (yes/no)	Measured as count of participants.	From baseline (week 0) to week 84
Number of participants with achievement of HbA1c < 5.7% (yes/no)	Measured as count of participants.	From baseline (week 0) to week 84
Change in fasting plasma glucose (FPG) measured as millimole per liter (mmol/L)	Measured as mmol/L.	From baseline (week 0) to week 84
Change in FPG measured as milligrams per deciliter (mg/dL)	Measured as mg/dL.	From baseline (week 0) to week 84
Ratio to baseline: change in fasting insulin	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in urinary albumin-to-creatinine ratio (UACR)	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in total cholesterol	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in high-density lipoprotein (HDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in low-density lipoprotein (LDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in very low-density lipoprotein (VLDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in non-HDL cholesterol	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in triglycerides	Measured as ratio.	From baseline (week 0) to week 84
Ratio to baseline: change in high-sensitivity C-reactive protein (hsCRP)	Measured as ratio.	From baseline (week 0) to week 84
Number of Treatment Emergent Adverse Events (TEAEs)	Measured as events.	From baseline (week 0) to week 84 and week 109
Number of Treatment Emergent Serious Adverse Events (TESAEs)	Measured as events.	From baseline (week 0) to week 84 and week 109
Number of TEAEs leading to permanent treatment discontinuation	Measured as events.	From baseline (week 0) to week 84 and week 109
Number of treatment-emergent clinically significant hypoglycaemic episodes (level 2) (< 3.0 millimole per liter [mmol/L] (54 milligrams per deciliter [mg/dL]), confirmed by a blood glucose (BG) meter)	Measured as episodes.	From baseline (week 0) to week 84 and week 109
Number of treatment-emergent severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold	Measured as episodes.	From baseline (week 0) to week 84 and week 109

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): December 12, 2028
• Study Completion (Estimated): January 26, 2029

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; semaglutide
• Other Study ID Numbers: NN9490-8028; U1111-1313-8017 (Other Identifier: World Health Organization (WHO)); 2024-520446-31 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No