Research Study to Compare Semaglutide Tablets With Empagliflozin or Metformin Tablets in People With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Efficacy and Safety of First Line Use of Oral Semaglutide 25 mg or 50 mg Once Daily Versus Empagliflozin 25 mg or Versus Metformin 2000 mg in Newly Diagnosed Treatment naïve Patients With Type 2 Diabetes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT06083675
• Other study ID #: NN9924-7663
• Secondary ID: U1111-1291-4976
• Status: Withdrawn
• Phase: Phase 3
• Start date: January 26, 2024
• Est. completion date: May 28, 2027

Study information

• Verified date: February 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares the medicines semaglutide with empagliflozin or metformin in people with newly diagnosed type 2 diabetes. This study will look mainly at how well participant's blood sugar and body weight are controlled when they are taking the study medicines. Participants will either get semaglutide tablets, empagliflozin tablets or metformin tablets. Which treatment participants will get is decided by chance. Currently, doses of 3 milligram (mg), 7 mg and 14 mg semaglutide tablets (Rybelsus) can be prescribed in some countries. 25 mg and 50 mg semaglutide tablets are new doses. 10 mg and 25 mg empagliflozin tablets (Jardiance) can be prescribed in some countries. 500 mg metformin tablets (STADA) can be prescribed in some countries. Participants will get 1 to 4 tablets per day for 104 weeks. The study will last for about 2 years and 7 weeks (111 weeks). Participants should not have been treated for weight management 90 days before screening or never been treated with any medicine for type 2 diabetes (except diabetes during pregnancy) before screening. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 28, 2027
• Est. primary completion date: January 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male or female.
• Age =18 and <60 years at the time of signing the informed consent.
• Diagnosed with type 2 diabetes mellitus within 24 months from the day of screening.
• HbA1c of 7.0-10.0% (53-86 millimoles per mole [mmol/mol])
• Body mass index =25.0 kilogram per square meter (kg/m^2)

Exclusion Criteria:

• Treatment with any medication for the indication of diabetes. Prior insulin treatment for gestational diabetes is allowed.
• Treatment with any medication for the indication of weight management 90 days prior to screening.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) <60 milliliters per minute per 1.73 meter sqaure (mL/min/1.73 m^2) at screening.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days 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.
• C-peptide <1.5 nanograms per milliliter (ng/mL) at screening.
• Positive insulinoma associated-protein 2 (IA-2) antibodies =7.5 Units/mL or anti-glutamic acid decarboxylase (anti-GAD) antibodies greater than (>) 5.0 international units per milliliter (IU/mL).
• Impaired liver function, defined as Alanine aminotransferase (ALT) =2.5 times or Bilirubin >1.5 times upper normal limit at screening.
• History of major surgical procedures involving the stomach potentially affecting absorption of trial products (example subtotal or total gastrectomy, sleeve gastrectomy, gastric bypass surgery) or current presence of gastrointestinal implant.
• Presence of clinically significant gastrointestinal disorders affecting absorption of drugs and/or nutrients, as judged by the investigator.
• Any contraindications for empagliflozin or metformin according to local labelling at the investigator's discretion

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Semaglutide
Administered as oral tablets.
• Empagliflozin
Administered as oral tablets.
• Metformin
Administered as oral tablets.

Locations

Country	Name	City	State
Brazil	Instituto de Ciências Farmacêuticas	Goiânia	Goias
Brazil	Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.	Porto Alegre	Rio Grande Do Sul
Brazil	CPCLIN - Centro de Pesquisas Clínicas	São Paulo	Sao Paulo
Brazil	CPQuali Pesquisa Clínica Ltda	São Paulo	Sao Paulo
Bulgaria	Individual Practice For Specialized Outpatient Medical Care Doctor Miglena Rizova Ltd.	Kyustendil
Bulgaria	"Aipsomcemd - Dr. Petya Georgieva" Eood	Plovdiv
Bulgaria	Diagnostic-Consultative Centre "Sveti Georgi" Eood	Plovdiv
Bulgaria	''Aipsomcidemd - Dr. Lilyana Bodurova-Troharova" Eood	Samokov
Bulgaria	"Medical center Medishtit Velisia" OOD	Stara Zagora
Bulgaria	Diagnostic Consulting Center 1 Velingrad EOOD	Velingrad
Bulgaria	MHAT- Hristo Botev AD	Vratsa
Croatia	Opca bolnica Karlovac	Karlovac
Croatia	Specijalna bolnica Krapinske Toplice - Endokrinologija	Krapinske Toplice
Croatia	Poliklinika SLAVONIJA OSIJEK	Osijek	Osjecko - Baranjska Županija
Croatia	Opca bolnica Pula	Pula
Croatia	Specijalna bolnica Medico	Rijeka
Greece	"Laiko" General Hospital of Athens	Athens
Greece	Iatriko Athinon 'Palaiou Falirou'	Athens
Greece	Iatriko Athinon (Athens Medical Canter)	Athens
Greece	Iatriko Psychicou Private Clinic	Athens
Greece	University Hospital of Athens ATTIKON	Haidari-Athens
Greece	University General Hospital of Ioannina,Internal Medicine	Ioannina
Greece	"Thermi" Private Hosital	Thessaloniki
Greece	EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes	Thessaloniki
Greece	General Hospital of Thessaloniki "G.Papanikolaou"	Thessaloniki
Greece	General Hospital of Thessaloniki 'G. Gennimatas	Thessaloniki
Hungary	ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.	Budapest
Hungary	Belinus Bt.	Debrecen
India	Navneeth Memorial Hospital	Ahmedabad	Gujrat
India	Swasthya Diabetes Care	Ahmedabad
India	Jawahar Lal Nehru Govt. Medical College	Ajmer	Rajasthan
India	Aligarh Muslim University	Aligarh
India	Lifecare Hospital and Research Centre	Bangalore	Karnataka
India	Ramaiah Memorial Hospital	Bangalore	Karnataka
India	Sparsh Hospital, Bhubaneshwar	Bhubaneshwar
India	M.V.Hospital for Diabetes Pvt. Ltd.	Chennai	Tamil Nadu
India	Maulana Azad Medical College	Delhi	New Delhi
India	Goa Medical College	Goa	Maharashtra
India	Endolife Specialty Hospitals	Guntur	Andhra Pradesh
India	Gandhi Hospital & Medical college	Hyderabad	Telengana
India	Osmania General Hospital	Hyderabad	A.p.
India	Yashoda hospital	Hyderabad	Telengana
India	TOTALL Diabetes Hormone Institute	Indore	Madhya Pradesh
India	Diabetes, Thyroid and Endocrine Centre	Jaipur	Rajasthan
India	Excel Endocrine Centre	Kolhapur	Maharashtra
India	BP Poddar Hospital	Kolkata,	West Bengal
India	Medanta Lucknow Hospital	Lucknow	Uttar Pradesh
India	Dayanand Medical College & Hospital_Ludhiana	Ludhiana	Punjab
India	All India Institute of Medical Sciences (AIIMS), Nagpur	Maharashtra
India	BSES MG hospital	Mumbai	Maharashtra
India	Seth GS Medical College & KEM Hospital	Mumbai	Maharashtra
India	K R Hospital	Mysuru	Karnataka
India	JIPMER	Puducherry
India	Lifepoint Multispecialty Hospital	Pune
India	Ashirwad Hospital and Research Centre	Thane	Maharashtra
India	Govt Medical College	Vadodara	Gujrat
India	Yalamanchi Hospitals and Research centres pvt ltd	Vijaywada	Andhra Pradesh
India	Mahatma Gandhi Memorial Hospital, Sherpura	Warangal
India	Acharya Vinoba Bhave Rural Hospital, Sawangi Meghe, Wardha	Wardha	Maharashtra
Malaysia	Klinik Kesihatan Bintulu	Bintulu
Malaysia	Klinik Kesihatan Greentown Ipoh	Ipoh
Malaysia	Klinik Kesihatan Cheras Baru	Kuala Lumpur
Malaysia	Hospital Melaka	Melaka
Malaysia	Klinik Kesihatan Kuang	Rawang	Selangor
Malaysia	Hospital Miri	Sarawak	Miri
Malaysia	Hospital Seri Manjung	Seri Manjung
Malaysia	Hospital Sultan Haji Ahmad Shah	Temerloh,Pahang
Mexico	Medical Care and Research S. A de C.V	Merida	Yucatan
Mexico	Eme Red Hospitalaria	Mérida	Yucatán
Mexico	FAICIC S. de R.L. de C.V.	Veracruz
Poland	NZOZ Vita-Diabetica Malgorzata Buraczyk	Bialystok	Podlaskie Voivodeship
Poland	Centrum Medyczne Intercor Sp. z o.o.	Bydgoszcz
Poland	Diab Serwis Popenda Spólka Jawna	Chorzów
Poland	NZOZ Euromedica	Grudziadz
Poland	Centra Medyczne Medyceusz Sp. z o.o.	Lódz
Poland	Etyka Osrodek Badan Klinicznych Tomasz Pesta S.K.A.	Olsztyn
Poland	ENDOPRACTICA W.Beker, D.Mielczarek, P.Mielczarek, J.Struzik spólka cywilna	Opole
Poland	Trialmed CRS	Piotrków Trybunalski	Lódzkie
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Spólka Partnerska Lekarzy	Poznan
Poland	ETG Siedlce	Siedlce	Masovian
Poland	Clinmedica Research sp. z o.o.	Skierniewice	Lodzkie
Poland	Centrum Medyczne Oporow	Wroclaw
Romania	Clinica Grivitei 224 S.R.L.	Braila
Romania	Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila	Bucharest	Bucurestii
Romania	SC Nutrilife SRL	Bucharest
Romania	Diabet Med SRL	Bucuresti
Romania	S.C. Dianutrilife Medica S.R.L.	Ploiesti
Romania	Clinica Korall S.R.L. Satu Mare	Satu-Mare
Romania	Sc Mediab Srl	Targu Mures	Mures
Romania	Sc Mediab Srl	Tirgu Mures	Mures
Serbia	Healthcare centre Zvezdara	Belgrade	RS
Serbia	Healthcare centre Kragujevac	Kragujevac	RS
Serbia	Healthcare centre Nis	Nis	RS
Thailand	Rajavithi Hospital	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok Noi	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Thammasat University Hospital	Klong Luang	Pathum Thani
Thailand	Songklanagarind Hospital	Songkla
United States	Hillcrest Family Health Center	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Croatia,  Greece,  Hungary,  India,  Malaysia,  Mexico,  Poland,  Romania,  Serbia,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glycated haemoglobin (HbA1c)	Measured in Percentage (%)-points.	From randomisation (week 0) to week 52
Secondary	Change in body weight	Measured in kilograms (kg).	From randomisation (week 0) to week 52
Secondary	Change in fasting plasma glucose (FPG)	Measured in millimoles per liter (mmol/L).	From randomisation (week 0) to week 52
Secondary	Change in 7 point self measured plasma glucose (SMPG) mean profile	Measured in mmol/L.	From randomisation (week 0) to week 52
Secondary	Change in 7-point self-measured plasma glucose (SMPG) mean post prandial increments	Measured in mmol/L.	From randomisation (week 0) to week 52
Secondary	Relative change in body weight	Measured in Percentage (%).	From randomisation (week 0) to week 52
Secondary	Change in waist circumference	Measured in centimeters (cm).	From randomisation (week 0) to week 52
Secondary	HbA1c less than or equal to (=) 6.5% (Yes/No)	Measured as count of participants.	At week 52
Secondary	HbA1c less than (<) 7% (Yes/No)	Measured as count of participants.	At week 52
Secondary	Body weight reduction greater than equal to ( =) 5% (Yes/No)	Measured as count of participants.	At week 52
Secondary	Body weight reduction =10% (Yes/No)	Measured as count of participants.	At week 52
Secondary	Body weight reduction =15% (Yes/No)	Measured as count of participants.	At week 52
Secondary	HbA1c <7.0% and body weight reduction =5% (Yes/No)	Measured as count of participants.	At week 52
Secondary	Change in systolic blood pressure	Measured in millimeters of mercury (mmHg).	From randomisation (week 0) to week 52
Secondary	Change in diastolic blood pressure	Measured in mmHg.	From randomisation (week 0) to week 52
Secondary	Change in High-sensitivity C-reactive protein (hsCRP)	Measured in milligrams per liter (mg/L).	From randomisation (week 0) to week 52
Secondary	Time to rescue medication	Measured in days.	From randomisation (week 0) to week 104
Secondary	Change in HbA1c	Measured in %-points.	From randomisation (week 0) to week 104
Secondary	Change in body weight	Measured in kg.	From randomisation (week 0) to week 104
Secondary	Change in FPG	Measured in mmol/L.	From randomisation (week 0) to week 104
Secondary	Change in 7 point SMPG mean profile	Measured in mmol/L.	From randomisation (week 0) to week 104
Secondary	Change in 7-point SMPG mean post prandial increments	Measured in mmol/L	From randomisation (week 0) to week 104
Secondary	Relative change in body weight	Measured in Percentage.	From randomisation (week 0) to week 104
Secondary	Change in waist circumference	Measured in cm.	From randomisation (week 0) to week 104
Secondary	HbA1c =6.5% (Yes/No)	Measured as count of participants.	At week 104
Secondary	HbA1c <7.0% (Yes/No)	Measured as count of participants.	At week 104
Secondary	Body weight reduction =5% (Yes/No)	Measured as count of participants.	At week 104
Secondary	Body weight reduction =10% (Yes/No)	Measured as count of participants.	At week 104
Secondary	Body weight reduction =15% (Yes/No)	Measured as count of participants.	At week 104
Secondary	HbA1c <7.0% and body weight reduction =5% (Yes/No)	Measured as count of participants.	At week 104
Secondary	Change in systolic blood pressure	Measured in mmHg.	From randomisation (week 0) to week 104
Secondary	Change in diastolic blood pressure	Measured in mmHg.	From randomisation (week 0) to week 104
Secondary	Change in hsCRP	Measured in mg/L.	From randomisation (week 0) to week 104
Secondary	Treatment emergent adverse events	Measured as count of events.	From randomisation (week 0) to week 52
Secondary	Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes	Measured as count of episodes.	From randomisation (week 0) to week 52
Secondary	Treatment emergent adverse events	Measured as count of events.	From randomisation (week 0) to follow-up visit (week 109)
Secondary	Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes	Measured as count of episodes.	From randomisation (week 0) to follow-up visit (week 109)
Secondary	Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain	CoEQ is a 19-item multidimensional patient reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control.	From randomisation (week 0) to week 52
Secondary	Change in CoEQ score - Craving for Savory domain	CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving savoury food subscale, higher score represents a greater level of craving.	From randomisation (week 0) to week 52
Secondary	Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) score - Physical function domain	IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100).	From randomisation (week 0) to week 52
Secondary	Change in American Heart Association (AHA) Life's Simple 7 summary score	The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health.	From randomisation (week 0) to week 52
Secondary	Change in CoEQ score - Craving Control domain	CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control.	From randomisation (week 0) to week 104
Secondary	Change in CoEQ score - Craving for Savory domain	CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving savoury food subscale, higher score represents a greater level of craving.	From randomisation (week 0) to week 104
Secondary	Change in IWQOL-Lite-CT score - Physical function domain	IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100).	From randomisation (week 0) to week 104
Secondary	Change in AHA Life's Simple 7 summary score	The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health.	From randomisation (week 0) to week 104