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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06083675
• Collaborator: (none)
• Enrollment: 912
• Locations: 102
• Arms: 4
• Anticipated Duration (Months): 40
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Semaglutide; Drug: Empagliflozin; Drug: Metformin	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 912 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Jan 26, 2024
• Anticipated Primary Completion Date: Jan 24, 2025
• Anticipated Study Completion Date: May 28, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide 25 mg Participants will receive 25 mg oral semaglutide once daily in maintenance period after dose escalation period.	Drug: Semaglutide; Administered as oral tablets.
Experimental: Semaglutide 50 mg Participants will receive 50 mg oral semaglutide once daily in maintenance period after dose escalation period.	Drug: Semaglutide; Administered as oral tablets.
Experimental: Empagliflozin 25 mg Participants will 25 mg empagliflozin oral once daily in maintenance period after dose escalation period.	Drug: Empagliflozin; Administered as oral tablets.
Experimental: Metformin 2000 mg Participants will receive metformin 1000 mg orally twice daily (total 2000 mg) in maintenance period after dose escalation period.	Drug: Metformin; Administered as oral tablets.

Outcome Measures

Primary Outcome Measures

1. Change in glycated haemoglobin (HbA1c) [From randomisation (week 0) to week 52]

   Measured in Percentage (%)-points.

Secondary Outcome Measures

1. Change in body weight [From randomisation (week 0) to week 52]

   Measured in kilograms (kg).

2. Change in fasting plasma glucose (FPG) [From randomisation (week 0) to week 52]

   Measured in millimoles per liter (mmol/L).

3. Change in 7 point self measured plasma glucose (SMPG) mean profile [From randomisation (week 0) to week 52]

   Measured in mmol/L.

4. Change in 7-point self-measured plasma glucose (SMPG) mean post prandial increments [From randomisation (week 0) to week 52]

   Measured in mmol/L.

5. Relative change in body weight [From randomisation (week 0) to week 52]

   Measured in Percentage (%).

6. Change in waist circumference [From randomisation (week 0) to week 52]

   Measured in centimeters (cm).

7. HbA1c less than or equal to (≤) 6.5% (Yes/No) [At week 52]

   Measured as count of participants.

8. HbA1c less than (<) 7% (Yes/No) [At week 52]

   Measured as count of participants.

9. Body weight reduction greater than equal to ( ≥) 5% (Yes/No) [At week 52]

   Measured as count of participants.

10. Body weight reduction ≥10% (Yes/No) [At week 52]

    Measured as count of participants.

11. Body weight reduction ≥15% (Yes/No) [At week 52]

    Measured as count of participants.

12. HbA1c <7.0% and body weight reduction ≥5% (Yes/No) [At week 52]

    Measured as count of participants.

13. Change in systolic blood pressure [From randomisation (week 0) to week 52]

    Measured in millimeters of mercury (mmHg).

14. Change in diastolic blood pressure [From randomisation (week 0) to week 52]

    Measured in mmHg.

15. Change in High-sensitivity C-reactive protein (hsCRP) [From randomisation (week 0) to week 52]

    Measured in milligrams per liter (mg/L).

16. Time to rescue medication [From randomisation (week 0) to week 104]

    Measured in days.

17. Change in HbA1c [From randomisation (week 0) to week 104]

    Measured in %-points.

18. Change in body weight [From randomisation (week 0) to week 104]

    Measured in kg.

19. Change in FPG [From randomisation (week 0) to week 104]

    Measured in mmol/L.

20. Change in 7 point SMPG mean profile [From randomisation (week 0) to week 104]

    Measured in mmol/L.

21. Change in 7-point SMPG mean post prandial increments [From randomisation (week 0) to week 104]

    Measured in mmol/L

22. Relative change in body weight [From randomisation (week 0) to week 104]

    Measured in Percentage.

23. Change in waist circumference [From randomisation (week 0) to week 104]

    Measured in cm.

24. HbA1c ≤6.5% (Yes/No) [At week 104]

    Measured as count of participants.

25. HbA1c <7.0% (Yes/No) [At week 104]

    Measured as count of participants.

26. Body weight reduction ≥5% (Yes/No) [At week 104]

    Measured as count of participants.

27. Body weight reduction ≥10% (Yes/No) [At week 104]

    Measured as count of participants.

28. Body weight reduction ≥15% (Yes/No) [At week 104]

    Measured as count of participants.

29. HbA1c <7.0% and body weight reduction ≥5% (Yes/No) [At week 104]

    Measured as count of participants.

30. Change in systolic blood pressure [From randomisation (week 0) to week 104]

    Measured in mmHg.

31. Change in diastolic blood pressure [From randomisation (week 0) to week 104]

    Measured in mmHg.

32. Change in hsCRP [From randomisation (week 0) to week 104]

    Measured in mg/L.

33. Treatment emergent adverse events [From randomisation (week 0) to week 52]

    Measured as count of events.

34. Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes [From randomisation (week 0) to week 52]

    Measured as count of episodes.

35. Treatment emergent adverse events [From randomisation (week 0) to follow-up visit (week 109)]

    Measured as count of events.

36. Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes [From randomisation (week 0) to follow-up visit (week 109)]

    Measured as count of episodes.

37. Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain [From randomisation (week 0) to week 52]

    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.

38. Change in CoEQ score - Craving for Savory domain [From randomisation (week 0) to week 52]

    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.

39. Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) score - Physical function domain [From randomisation (week 0) to week 52]

    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).

40. Change in American Heart Association (AHA) Life's Simple 7 summary score [From randomisation (week 0) to week 52]

    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.

41. Change in CoEQ score - Craving Control domain [From randomisation (week 0) to week 104]

    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.

42. Change in CoEQ score - Craving for Savory domain [From randomisation (week 0) to week 104]

    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.

43. Change in IWQOL-Lite-CT score - Physical function domain [From randomisation (week 0) to week 104]

    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).

44. Change in AHA Life's Simple 7 summary score [From randomisation (week 0) to week 104]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Toluca Lake	California	United States	91602
2	Novo Nordisk Investigational Site	Boston	Massachusetts	United States	02115
3	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
4	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
5	Novo Nordisk Investigational Site	Cedar Park	Texas	United States	78613
6	Novo Nordisk Investigational Site	Houston	Texas	United States	77061
7	Novo Nordisk Investigational Site	Waco	Texas	United States	76708
8	Novo Nordisk Investigational Site	Goiânia	Goias	Brazil	74935-330
9	Novo Nordisk Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90430-001
10	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-000
11	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-200
12	Novo Nordisk Investigational Site	Kyustendil		Bulgaria	2500
13	Novo Nordisk Investigational Site	Plovdiv		Bulgaria	4002
14	Novo Nordisk Investigational Site	Plovdiv		Bulgaria	4018
15	Novo Nordisk Investigational Site	Samokov		Bulgaria	1000
16	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6000
17	Novo Nordisk Investigational Site	Velingrad		Bulgaria	4600
18	Novo Nordisk Investigational Site	Vratsa		Bulgaria	3000
19	Novo Nordisk Investigational Site	Osijek	Osječko - Baranjska Županija	Croatia	31000
20	Novo Nordisk Investigational Site	Karlovac		Croatia	47000
21	Novo Nordisk Investigational Site	Krapinske Toplice		Croatia	49217
22	Novo Nordisk Investigational Site	Pula		Croatia	52100
23	Novo Nordisk Investigational Site	Rijeka		Croatia	51000
24	Novo Nordisk Investigational Site	Athens		Greece	115 25
25	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
26	Novo Nordisk Investigational Site	Athens		Greece	GR-15125
27	Novo Nordisk Investigational Site	Athens		Greece	GR-17562
28	Novo Nordisk Investigational Site	Haidari-Athens		Greece	GR-12462
29	Novo Nordisk Investigational Site	Ioannina		Greece	45500
30	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54635
31	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54643
32	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57001
33	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57010
34	Novo Nordisk Investigational Site	Szeged	Csongrád-Csanád	Hungary	H-6725
35	Novo Nordisk Investigational Site	Budapest		Hungary	1089
36	Novo Nordisk Investigational Site	Budapest		Hungary	1132
37	Novo Nordisk Investigational Site	Debrecen		Hungary	4025
38	Novo Nordisk Investigational Site	Nyíregyháza		Hungary	4405
39	Novo Nordisk Investigational Site	Hyderabad	A.p.	India	500 063
40	Novo Nordisk Investigational Site	Guntur	Andhra Pradesh	India	522001
41	Novo Nordisk Investigational Site	Vijaywada	Andhra Pradesh	India	520002
42	Novo Nordisk Investigational Site	Ahmedabad	Gujrat	India	380009
43	Novo Nordisk Investigational Site	Vadodara	Gujrat	India	390001
44	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560054
45	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560092
46	Novo Nordisk Investigational Site	Mysuru	Karnataka	India	570001
47	Novo Nordisk Investigational Site	Indore	Madhya Pradesh	India	452010
48	Novo Nordisk Investigational Site	Goa	Maharashtra	India	403 202
49	Novo Nordisk Investigational Site	Kolhapur	Maharashtra	India	416008
50	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
51	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400058
52	Novo Nordisk Investigational Site	Thane	Maharashtra	India	421004
53	Novo Nordisk Investigational Site	Wardha	Maharashtra	India	442001
54	Novo Nordisk Investigational Site	Delhi	New Delhi	India	110002
55	Novo Nordisk Investigational Site	Ludhiana	Punjab	India	141001
56	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302006
57	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600 013
58	Novo Nordisk Investigational Site	Hyderabad	Telengana	India	500003
59	Novo Nordisk Investigational Site	Hyderabad	Telengana	India	500082
60	Novo Nordisk Investigational Site	Lucknow	Uttar Pradesh	India	226030
61	Novo Nordisk Investigational Site	Kolkata,	West Bengal	India	700053
62	Novo Nordisk Investigational Site	Ahmedabad		India	390013
63	Novo Nordisk Investigational Site	Aligarh		India	202002
64	Novo Nordisk Investigational Site	Bhubaneshwar		India	751007
65	Novo Nordisk Investigational Site	Maharashtra		India	441108
66	Novo Nordisk Investigational Site	Puducherry		India	605006
67	Novo Nordisk Investigational Site	Pune		India	411057
68	Novo Nordisk Investigational Site	Warangal		India	506002
69	Novo Nordisk Investigational Site	Sarawak	Miri	Malaysia	98000
70	Novo Nordisk Investigational Site	Bintulu		Malaysia	97000
71	Novo Nordisk Investigational Site	Ipoh		Malaysia	30450
72	Novo Nordisk Investigational Site	Melaka		Malaysia	75400
73	Novo Nordisk Investigational Site	Temerloh,Pahang		Malaysia	28000
74	Novo Nordisk Investigational Site	Skierniewice	Lodzkie	Poland	96-100
75	Novo Nordisk Investigational Site	Siedlce	Masovian	Poland	08-110
76	Novo Nordisk Investigational Site	Bialystok	Podlaskie Voivodeship	Poland	15-879
77	Novo Nordisk Investigational Site	Bydgoszcz		Poland	85-605
78	Novo Nordisk Investigational Site	Chorzów		Poland	41-500
79	Novo Nordisk Investigational Site	Grudziadz		Poland	86-300
80	Novo Nordisk Investigational Site	Olsztyn		Poland	10-117
81	Novo Nordisk Investigational Site	Opole		Poland	45-301
82	Novo Nordisk Investigational Site	Poznań		Poland	61-853
83	Novo Nordisk Investigational Site	Wroclaw		Poland	52-416
84	Novo Nordisk Investigational Site	Łódź		Poland	91-053
85	Novo Nordisk Investigational Site	Piotrków Trybunalski	Łódzkie	Poland	97-300
86	Novo Nordisk Investigational Site	Bucharest	Bucurestii	Romania	020475
87	Novo Nordisk Investigational Site	Targu Mures	Mures	Romania	540142
88	Novo Nordisk Investigational Site	Tirgu Mures	Mures	Romania	540142
89	Novo Nordisk Investigational Site	Braila		Romania	810197
90	Novo Nordisk Investigational Site	Bucharest		Romania	013764
91	Novo Nordisk Investigational Site	Bucuresti		Romania	050913
92	Novo Nordisk Investigational Site	Ploiesti		Romania	100561
93	Novo Nordisk Investigational Site	Satu-Mare		Romania	440055
94	Novo Nordisk Investigational Site	Belgrade	RS	Serbia	11050
95	Novo Nordisk Investigational Site	Kragujevac	RS	Serbia	34000
96	Novo Nordisk Investigational Site	Nis	RS	Serbia	18000
97	Novo Nordisk Investigational Site	Bangkok Noi	Bangkok	Thailand	10700
98	Novo Nordisk Investigational Site	Klong Luang	Pathum Thani	Thailand	12120
99	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
100	Novo Nordisk Investigational Site	Chiang Mai		Thailand	50200
101	Novo Nordisk Investigational Site	Khon Kaen		Thailand	40002
102	Novo Nordisk Investigational Site	Songkla		Thailand	90110

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT06083675
• Other Study ID Numbers: NN9924-7663; U1111-1291-4976
• First Posted: Oct 16, 2023
• Last Update Posted: Oct 16, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Empagliflozin

Study Results

No Results Posted as of Oct 16, 2023