SUSTAIN 11: A Research Study to Compare Semaglutide to Insulin Aspart, When Taken Together With Metformin and Insulin Glargine, in People With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03689374
• Collaborator: (none)
• Enrollment: 2,274
• Locations: 210
• Arms: 2
• Actual Duration (Months): 28.7
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will compare the effect of semaglutide once weekly to insulin aspart 3 times daily as add on to metformin and insulin glargine in people with type 2 diabetes. Participants will either get insulin glargine and semaglutide or insulin glargine and insulin aspart - which treatment the participant get is decided by chance. Insulin glargine is taken once a day and semaglutide once a week. Insulin aspart is taken three times per day before a meal. All three medicines come in pre-filled pens for injection under the skin. The study will last for about 71 weeks. If participant's blood sugar gets under or over certain values participant will only participate in 14 weeks. The study doctor will inform the participant about this. The participant will have 15 clinic visits and 22 phone calls with the study doctor.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Semaglutide; Drug: Insulin aspart; Drug: Insulin glargine U100	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2274 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes A 52-week, Multi-centre, Multinational, Open-label, Active-controlled, Two Armed, Parallel-group, Randomised Trial in Subjects With Type 2 Diabetes
• Actual Study Start Date: Oct 1, 2018
• Actual Primary Completion Date: Feb 22, 2021
• Actual Study Completion Date: Feb 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide Run-in period (12 weeks): subjects will be treated with metformin and insulin glargine (IGlar) U100. Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in will receive semaglutide for 52 weeks in addition to metformin and IGlar U100. Metformin will be considered as background therapy during the trial.	Drug: Semaglutide; Subjects will receive subcutaneous (s.c., under the skin) injections of semaglutide once weekly (OW) with a dose of 0.25 mg. The dose should be increased after four weeks to 0.5 mg semaglutide. After 4 more weeks the dose can be increased to 1.0 mg semaglutide if the study doctor decides and further dose adjusted throughout the study.; Drug: Insulin glargine U100; Run-in period: Subjects will receive s.c. injections of IGlar U100 OD in accordance with the approved local label of IGlar U100. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.0-6.9 mmol/L)
Active Comparator: Insulin aspart Run-in period (12 weeks): subjects will be treated with metformin and insulin IGlar U100. Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in receive insulin aspart for 52 weeks in addition to metformin and IGlar U100. Metformin will be considered as background therapy during the trial.	Drug: Insulin aspart; Subjects should initiate treatment with 4U of Insulin aspart (s.c. injections) before each main meal, three times daily (TID). The dose will be adjusted individually based on pre-prandial and bedtime self measured plasma glucose (SMPG) from the preceding 3 days; Drug: Insulin glargine U100; Run-in period: Subjects will receive s.c. injections of IGlar U100 OD in accordance with the approved local label of IGlar U100. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.0-6.9 mmol/L)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycated Haemoglobin (HbA1c) [Baseline (week 0), week 52]

   Change from baseline in HbA1c at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

Secondary Outcome Measures

1. Time to First Event Adjudication Committee (EAC)-Confirmed Severe Hypoglycaemic Episode American Diabetes Association (ADA) From Randomization up to Week 52 [From randomization (week 0) up to week 52]

   First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with plasma glucose (PG) less than or equal to (<=) 3.9 millimoles per liter (mmol/L) (70 milligrams per deciliter (mg/dL)). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

2. Time to First Event Adjudication Committee-confirmed Severe Hypoglycaemic Episode (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening Randomization up to Week 52 [From randomization (week 0) up to week 52]

   First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

3. Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) From Randomization to Week 52 [From randomization (week 0) to week 52]

   Number of EAC-confirmed severe hypoglycaemic episodes from randomization (week 0) up to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

4. Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose (BG) Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose Less Than (<) 3.1 mmol/L (56 mg/dL)) From Randomization to Week 52 [From randomization (week 0) to week 52]

   Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <3.1 mmol/L (56 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode, that was BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

5. Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose <= 3.9 mmol/L (70 mg/dL)) From Randomization to Week 52 [From randomization (week 0) to week 52]

   Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <=3.9 mmol/L (70 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode during which symptoms of hypoglycaemia were not accompanied by a PG determination but that was presumably caused by a PG concentration <= 3.9 mmol/L (70 mg/dL). Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

6. Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening From Randomization to Week 52 [From randomization (week 0) to week 52]

   Number of EAC-confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life-threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

7. Number of Event Adjudication Committee-confirmed Severe (ADA) or Clinically Significant Hypoglycaemic Episodes (Plasma Glucose < 3.0 mmol/L (54 mg/dL)) From Randomization to Week 52 [From randomization (week 0) to week 52]

   Number of EAC-confirmed severe or clinically significant hypoglycaemic episodes (plasma glucose < 3.0 mmol/L (54 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Hypoglycaemic episode with plasma glucose < 3.0 mmol/L (54 mg/dL)) was considered as clinically significant. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

8. Daily Basal Insulin Dose at Week 52 [At week 52]

   Daily basal insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

9. Total Daily Insulin Dose at Week 52 [At week 52]

   Total daily insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

10. Change From Baseline to Week 52 in Body Weight (Kilogram (kg)) [Baseline (week 0), week 52]

    Change from baseline in body weight at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

11. Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG) [Baseline (week 0), week 52]

    Change from baseline in FPG at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

12. Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile (SMPG ): Mean 7-point Profile (7-PP) [Baseline (week 0), week 52]

    Change from baseline in 7-point self-measured plasma glucose profile: mean 7-PP at week 52 is presented. All participants were instructed to perform 7-point SMPG profiles before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal (dinner), 90 minutes after the start of main evening meal (dinner) and at bedtime. The measurements were to be performed before any injection of bolus insulin and just before the start of the meal (breakfast, lunch or main evening meal), and values measured before breakfast were performed in a fasting condition. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

13. Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile: Mean Post-prandial Increment (Over All Meals) [Baseline (week 0), week 52]

    Change from baseline in 7-point SMPG profile: mean post-prandial increment (over all meals) at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

14. Change From Baseline to Week 52 in Body Mass Index (BMI) [Baseline (week 0), week 52]

    Change from baseline in BMI at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

15. Change From Baseline to Week 52 in Waist Circumference [Baseline (week 0), week 52]

    Change from baseline in waist circumference at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

16. Change From Baseline to Week 52 in Body Weight (Percentage): Ratio to Baseline [Baseline (week 0), week 52]

    Change from baseline in body weight (measured in percentage) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

17. Change From Baseline to Week 52 in Fasting Blood Lipids: Total Cholesterol (Ratio to Baseline) [Baseline (week 0), week 52]

    Change from baseline in total cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

18. Change From Baseline to Week 52 in Fasting Blood Lipids: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline) [Baseline (week 0), week 52]

    Change from baseline in LDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

19. Change From Baseline to Week 52 in Fasting Blood Lipids: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline) [Baseline (week 0), week 52]

    Change from baseline in HDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

20. Change From Baseline to Week 52 in Fasting Blood Lipids: Triglycerides (Ratio to Baseline) [Baseline (week 0), week 52]

    Change from baseline in triglycerides (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

21. Change From Baseline to Week 52 in Systolic and Diastolic Blood Pressure [Baseline (week 0), week 52]

    Change from baseline in systolic and diastolic blood pressure at week 52 are presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

22. Change From Baseline to Week 52 in Pulse Rate [Baseline (week 0), week 52]

    Change from baseline in pulse rate at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

23. Change From Baseline to Week 52 in 36-item Short Form Health Survey Version 2 (SF-36v2): Total Summary Scores (Physical Component and Mental Component) and Scores From the 8 Domains [Baseline (week 0), week 52]

    SF-36v2 is 36-item patient-reported survey of patient health to measure participant's overall health-related quality of life (HRQoL). It has 36 items: 8 domains of physical, mental health status (physical functioning, role physical health (range:21.23-57.16), bodily pain (range: 21.68-62.00), general health (range: 18.95-66.50), vitality (range: 22.89-70.42), social functioning (range: 17.23-57.34), role emotional problem (range: 14.39-56.17) and mental health (range: 11.63-63.95)) and 2 total summary scores: physical components summary (range: 7.32-70.14) and mental components summary (range: 5.79-69.91) calculated from domain scores. All 10 scores range from 5.79-70.42 . Higher scores indicated a better health state. Change from baseline in SF-36v2, 2 summary and 8 domains scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from date of first dose of trial product (week 0) to last date on trial product with a visit window of +7 days (week 52).

24. Change From Baseline to Week 52 in Diabetes Quality of Life Clinical Trial Questionnaire (DQLCTQ-R): Scores From the 8 Domains [Baseline (week 0), week 52]

    The DQLCTQ-R questionnaire was used to assess participants' HRQoL. The DQLCTQ-R questionnaire contains 57 items and measures and provide scores for the 8 domains (physical function, energy or fatigue, health distress, mental health, satisfaction, treatment satisfaction, treatment flexibility and frequency of symptoms). The 8 domain scores related to DQLCTQ-R are measured on a scale from 0-100. For all scores, higher values indicated better health status. Change from baseline in DQLCTQ-R 8 domain scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent

• Diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening

• Treated with basal insulin once daily or twice daily for greater than or equal to 90 days prior to the day of screening

• Stable daily dose for 90 days prior to the day of screening of the following anti-diabetic drugs or combination regimens: Any metformin formulations (greater than or equal to 1500 mg to less than or equal to 3000 mg or maximum tolerated or effective dose documented in subject's medical record), alone or in combination (including fixed-dose drug combination) with up to one additional of the following oral antidiabetic drugs: sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors or alpha-glucosidase inhibitors

• Glycated haemoglobin (HbA1c) of greater than 7.5% to less than or less than or equal to 10.0% (greater than 58 mmol/mol to less than or equal to 86 mmol/mol)

Exclusion Criteria:

• History or presence of pancreatitis (acute or chronic)

• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening

• Subjects presently classified as being in New York Heart Association Class IV

• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term bolus insulin treatment for a maximum of 14 days prior to the day of screening is allowed

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (for example, optometrist) within the past 90 days prior to run-in

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Banja Luka		Bosnia and Herzegovina	78000
2	Novo Nordisk Investigational Site	Sarajevo		Bosnia and Herzegovina	71000
3	Novo Nordisk Investigational Site	Tuzla		Bosnia and Herzegovina	75000
4	Novo Nordisk Investigational Site	Burgas		Bulgaria	8000
5	Novo Nordisk Investigational Site	Byala		Bulgaria	7100
6	Novo Nordisk Investigational Site	Dimitrovgrad		Bulgaria	6400
7	Novo Nordisk Investigational Site	Plovdiv		Bulgaria	4002
8	Novo Nordisk Investigational Site	Ruse		Bulgaria	7000
9	Novo Nordisk Investigational Site	Sofia		Bulgaria	1632
10	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6000
11	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6001
12	Novo Nordisk Investigational Site	Varna		Bulgaria	9010
13	Novo Nordisk Investigational Site	Karlovac		Croatia	47000
14	Novo Nordisk Investigational Site	Osijek		Croatia	31 000
15	Novo Nordisk Investigational Site	Pula		Croatia	52100
16	Novo Nordisk Investigational Site	Rijeka		Croatia	51 000
17	Novo Nordisk Investigational Site	Varazdin		Croatia	42 000
18	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
19	Novo Nordisk Investigational Site	Beroun		Czechia	26601
20	Novo Nordisk Investigational Site	Brno		Czechia	602 00
21	Novo Nordisk Investigational Site	Kladno - Krocehlavy		Czechia	272 01
22	Novo Nordisk Investigational Site	Mlada Boleslav		Czechia	293 50
23	Novo Nordisk Investigational Site	Nachod		Czechia	54701
24	Novo Nordisk Investigational Site	Olomouc		Czechia	77900
25	Novo Nordisk Investigational Site	Plzeň		Czechia	301 00
26	Novo Nordisk Investigational Site	Prostejov		Czechia	79601
27	Novo Nordisk Investigational Site	Pärnu		Estonia	80018
28	Novo Nordisk Investigational Site	Tallinn		Estonia	10138
29	Novo Nordisk Investigational Site	Tallinn		Estonia	10617
30	Novo Nordisk Investigational Site	Tallinn		Estonia	13419
31	Novo Nordisk Investigational Site	Viljandi		Estonia	71024
32	Novo Nordisk Investigational Site	Bad Kreuznach		Germany	55545
33	Novo Nordisk Investigational Site	Bad Mergentheim		Germany	97980
34	Novo Nordisk Investigational Site	Berlin		Germany	10437
35	Novo Nordisk Investigational Site	Berlin		Germany	10629
36	Novo Nordisk Investigational Site	Berlin		Germany	10787
37	Novo Nordisk Investigational Site	Berlin		Germany	13597
38	Novo Nordisk Investigational Site	Eisenach		Germany	99817
39	Novo Nordisk Investigational Site	Essen		Germany	45136
40	Novo Nordisk Investigational Site	Essen		Germany	45355
41	Novo Nordisk Investigational Site	Essen		Germany	45359
42	Novo Nordisk Investigational Site	Esslingen		Germany	73728
43	Novo Nordisk Investigational Site	Falkensee		Germany	14612
44	Novo Nordisk Investigational Site	Friedrichsthal		Germany	66299
45	Novo Nordisk Investigational Site	Hamburg		Germany	22041
46	Novo Nordisk Investigational Site	Hamburg		Germany	22607
47	Novo Nordisk Investigational Site	Hohenmölsen		Germany	06679
48	Novo Nordisk Investigational Site	Jerichow		Germany	39319
49	Novo Nordisk Investigational Site	Kiel Kronshagen		Germany	24119
50	Novo Nordisk Investigational Site	Leipzig		Germany	04249
51	Novo Nordisk Investigational Site	Münster		Germany	48145
52	Novo Nordisk Investigational Site	Münster		Germany	48153
53	Novo Nordisk Investigational Site	Oldenburg I. Holst		Germany	23758
54	Novo Nordisk Investigational Site	Pohlheim		Germany	35415
55	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
56	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
57	Novo Nordisk Investigational Site	Schwabenheim		Germany	55270
58	Novo Nordisk Investigational Site	Schweinfurt		Germany	97421
59	Novo Nordisk Investigational Site	Stuhr		Germany	28816
60	Novo Nordisk Investigational Site	Stuttgart		Germany	70199
61	Novo Nordisk Investigational Site	Stuttgart		Germany	70378
62	Novo Nordisk Investigational Site	Villingen-Schwenningen		Germany	78048
63	Novo Nordisk Investigational Site	Alexandroupolis		Greece	GR-68100
64	Novo Nordisk Investigational Site	Athens		Greece	115 21
65	Novo Nordisk Investigational Site	Athens		Greece	115 25
66	Novo Nordisk Investigational Site	Athens		Greece	11522
67	Novo Nordisk Investigational Site	Athens		Greece	GR-115 27
68	Novo Nordisk Investigational Site	Athens		Greece	GR-11521
69	Novo Nordisk Investigational Site	Athens		Greece	GR-11526
70	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
71	Novo Nordisk Investigational Site	Larissa		Greece	GR-41110
72	Novo Nordisk Investigational Site	Piraeus		Greece	GR-18536
73	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54642
74	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54643
75	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57001
76	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57010
77	Novo Nordisk Investigational Site	Budapest		Hungary	1033
78	Novo Nordisk Investigational Site	Budapest		Hungary	1042
79	Novo Nordisk Investigational Site	Budapest		Hungary	1089
80	Novo Nordisk Investigational Site	Gyula		Hungary	5700
81	Novo Nordisk Investigational Site	Nagykanizsa		Hungary	8800
82	Novo Nordisk Investigational Site	Pécs		Hungary	7623
83	Novo Nordisk Investigational Site	Salgótarján		Hungary	3100
84	Novo Nordisk Investigational Site	Szeged		Hungary	H-6725
85	Novo Nordisk Investigational Site	Zalaegerszeg		Hungary	8900
86	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500072
87	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India
88	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560034
89	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560092
90	Novo Nordisk Investigational Site	Indore	Madhya Pradesh	India	452010
91	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
92	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400058
93	Novo Nordisk Investigational Site	Nagpur	Maharashtra	India	440010
94	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411040
95	Novo Nordisk Investigational Site	Delhi	New Delhi	India	110002
96	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
97	Novo Nordisk Investigational Site	Bhubaneswar	Orissa	India	751005
98	Novo Nordisk Investigational Site	Bhubaneswar	Orissa	India	751019
99	Novo Nordisk Investigational Site	Chandigarh	Punjab	India	160012
100	Novo Nordisk Investigational Site	Ludhiana	Punjab	India	141001
101	Novo Nordisk Investigational Site	Mohali	Punjab	India	160062
102	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302006
103	Novo Nordisk Investigational Site	Madurai	Tamil Nadu	India	625 020
104	Novo Nordisk Investigational Site	Hyderabad	Telengana	India	500003
105	Novo Nordisk Investigational Site	Hyderbad	Telengana	India	500 012
106	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
107	Novo Nordisk Investigational Site	New Delhi		India	110001
108	Novo Nordisk Investigational Site	Jelgava		Latvia	LV-3001
109	Novo Nordisk Investigational Site	Ogre		Latvia	LV-5001
110	Novo Nordisk Investigational Site	Riga		Latvia	LV-1002
111	Novo Nordisk Investigational Site	Riga		Latvia	LV-1024
112	Novo Nordisk Investigational Site	Sigulda		Latvia	LV-2150
113	Novo Nordisk Investigational Site	Talsi		Latvia	LV-3201
114	Novo Nordisk Investigational Site	Kaunas		Lithuania	48259
115	Novo Nordisk Investigational Site	Kaunas		Lithuania	49449
116	Novo Nordisk Investigational Site	Kaunas		Lithuania	50009
117	Novo Nordisk Investigational Site	Panevezys		Lithuania	37355
118	Novo Nordisk Investigational Site	Vilnius		Lithuania	04318
119	Novo Nordisk Investigational Site	Vilnius		Lithuania	08661
120	Novo Nordisk Investigational Site	Skopje		North Macedonia	1000
121	Novo Nordisk Investigational Site	Bialystok		Poland	15-276
122	Novo Nordisk Investigational Site	Bialystok		Poland	15-351
123	Novo Nordisk Investigational Site	Bialystok		Poland	15-704
124	Novo Nordisk Investigational Site	Gorzow Wielkopolski		Poland	66-400
125	Novo Nordisk Investigational Site	Lodz		Poland	94-074 LODZ
126	Novo Nordisk Investigational Site	Lublin		Poland	20-044
127	Novo Nordisk Investigational Site	Lublin		Poland	20-090
128	Novo Nordisk Investigational Site	Lublin		Poland	20-538
129	Novo Nordisk Investigational Site	Poznan		Poland	60-589
130	Novo Nordisk Investigational Site	Poznan		Poland	61-251
131	Novo Nordisk Investigational Site	Poznan		Poland	61-853
132	Novo Nordisk Investigational Site	Pulawy		Poland	24-100
133	Novo Nordisk Investigational Site	Ruda Slaska		Poland	41-709
134	Novo Nordisk Investigational Site	Siedlce		Poland	08-110
135	Novo Nordisk Investigational Site	Skorzewo		Poland	60-185
136	Novo Nordisk Investigational Site	Warsaw		Poland	00-465
137	Novo Nordisk Investigational Site	Wierzchoslawice		Poland	33-122
138	Novo Nordisk Investigational Site	Wroclaw		Poland	50-127
139	Novo Nordisk Investigational Site	Wroclaw		Poland	51-685
140	Novo Nordisk Investigational Site	Zabrze		Poland	41-800
141	Novo Nordisk Investigational Site	Almada		Portugal	2805-267
142	Novo Nordisk Investigational Site	Braga		Portugal	4710-243
143	Novo Nordisk Investigational Site	Coimbra		Portugal	3000-561
144	Novo Nordisk Investigational Site	Lisboa		Portugal	1250-230
145	Novo Nordisk Investigational Site	Loures		Portugal	2674-514
146	Novo Nordisk Investigational Site	Porto		Portugal	4200-319
147	Novo Nordisk Investigational Site	Setubal		Portugal	2910-446
148	Novo Nordisk Investigational Site	Cluj Napoca	Cluj	Romania	400006
149	Novo Nordisk Investigational Site	Targoviste	Dambovita	Romania	130086
150	Novo Nordisk Investigational Site	Targu Mures	Mures	Romania	540098
151	Novo Nordisk Investigational Site	Ploiesti	Prahova	Romania	100018
152	Novo Nordisk Investigational Site	Brasov		Romania	500101
153	Novo Nordisk Investigational Site	Brasov		Romania	500283
154	Novo Nordisk Investigational Site	Galati		Romania	800578
155	Novo Nordisk Investigational Site	Belgrade		Serbia	11000
156	Novo Nordisk Investigational Site	Belgrade		Serbia	11080
157	Novo Nordisk Investigational Site	Kragujevac		Serbia	34000
158	Novo Nordisk Investigational Site	Nis		Serbia	18000
159	Novo Nordisk Investigational Site	Novi Sad		Serbia	21000
160	Novo Nordisk Investigational Site	Zajecar		Serbia	19000
161	Novo Nordisk Investigational Site	Bardejov		Slovakia	08501
162	Novo Nordisk Investigational Site	Bratislava		Slovakia	811 08
163	Novo Nordisk Investigational Site	Bratislava		Slovakia	81108
164	Novo Nordisk Investigational Site	Bratislava		Slovakia	82606
165	Novo Nordisk Investigational Site	Dolny Kubin		Slovakia	02601
166	Novo Nordisk Investigational Site	Levice		Slovakia	93401
167	Novo Nordisk Investigational Site	Lubochna		Slovakia	03491
168	Novo Nordisk Investigational Site	Martin		Slovakia	03601
169	Novo Nordisk Investigational Site	Presov		Slovakia	080 01
170	Novo Nordisk Investigational Site	Prievidza		Slovakia	97101
171	Novo Nordisk Investigational Site	Sabinov		Slovakia	08301
172	Novo Nordisk Investigational Site	Brezice		Slovenia	8250
173	Novo Nordisk Investigational Site	Jesenice		Slovenia	SI-4270
174	Novo Nordisk Investigational Site	Koper		Slovenia	SI-6000
175	Novo Nordisk Investigational Site	Murska Sobota		Slovenia	SI-9000
176	Novo Nordisk Investigational Site	Nova Gorica		Slovenia	SI-5000
177	Novo Nordisk Investigational Site	Nova Gorica		Slovenia	SI-5290
178	Novo Nordisk Investigational Site	Benoni	Gauteng	South Africa	1501
179	Novo Nordisk Investigational Site	Cosmo City	Gauteng	South Africa	2188
180	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1818
181	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2198
182	Novo Nordisk Investigational Site	Lenasia	Gauteng	South Africa	1827
183	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0002
184	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0122
185	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4092
186	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
187	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal	South Africa	4170
188	Novo Nordisk Investigational Site	Almeria		Spain	04009
189	Novo Nordisk Investigational Site	Antequera		Spain	29200
190	Novo Nordisk Investigational Site	Córdoba		Spain	14004
191	Novo Nordisk Investigational Site	Fuenlabrada - Madrid		Spain	28942
192	Novo Nordisk Investigational Site	Madrid		Spain	28006
193	Novo Nordisk Investigational Site	Málaga		Spain	29006
194	Novo Nordisk Investigational Site	Palma de Mallorca		Spain	07010
195	Novo Nordisk Investigational Site	Segovia		Spain	40002
196	Novo Nordisk Investigational Site	Sevilla		Spain	41003
197	Novo Nordisk Investigational Site	Adana		Turkey	01130
198	Novo Nordisk Investigational Site	Ankara		Turkey	06500
199	Novo Nordisk Investigational Site	Antalya		Turkey	07058
200	Novo Nordisk Investigational Site	Denizli		Turkey	20070
201	Novo Nordisk Investigational Site	Erzurum		Turkey	25240
202	Novo Nordisk Investigational Site	Istanbul		Turkey	34303
203	Novo Nordisk Investigational Site	Istanbul		Turkey	34390
204	Novo Nordisk Investigational Site	Istanbul		Turkey	34400
205	Novo Nordisk Investigational Site	Istanbul		Turkey	34722
206	Novo Nordisk Investigational Site	Istanbul		Turkey	34760
207	Novo Nordisk Investigational Site	Istanbul		Turkey	34899
208	Novo Nordisk Investigational Site	Izmir		Turkey	35100
209	Novo Nordisk Investigational Site	Izmir		Turkey	35340
210	Novo Nordisk Investigational Site	Trabzon		Turkey	61080

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Jul 8, 2020
• Statistical Analysis Plan - Jan 25, 2021

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03689374
• Other Study ID Numbers: NN9535-4386; U1111-1200-0164; 2017-003219-20
• First Posted: Sep 28, 2018
• Last Update Posted: Jul 6, 2022
• Last Verified: Jun 1, 2022

• 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
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Aspart

Study Results

Participant Flow

Recruitment Details

The trial was conducted at 209 sites in 21 countries: Bosnia-Herzegovina (3 sites), Bulgaria (9 sites), Croatia (7 sites), Czech Republic (7 sites), Estonia (5 sites), Germany (25 sites), Greece (14 sites), Hungary (8 sites), India (20 sites), Latvia (7 sites), Lithuania (6 sites), Macedonia (3 sites), Poland (20 sites), Portugal (6 sites), Romania (7 sites), Serbia (14 sites), Slovakia (9 sites), Slovenia (6 sites), South Africa (11 sites), Spain (8 sites) and Turkey (14 sites).

Pre-assignment Detail

This trial consisted of 12-week run-in, 52-week treatment period and participants were followed up 5 weeks for safety. Participants were randomized 1:1 to receive treatment with: metformin + insulin glargine (IGlar) U100 + once-weekly semaglutide subcutaneously (s.c). or metformin + insulin glargine U100 + mealtime insulin aspart s.c. three times daily.

Arm/Group Title	All Participants	Semaglutide	Insulin Aspart
Arm/Group Description	During run-in period insulin glargine in combination with metformin was to be optimized. All enrolled participants received metformin orally and IGlar U100 s.c. injection in run-in period. Metformin was optimized in dose range of greater than or equal to (>=) 1500 milligrams (mg) to less than or equal to (<=) 3000 mg. After run-in period, participants were randomized 1:1 to receive add-on treatment with semaglutide once weekly or insulin aspart three times daily (TID) in treatment period.	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Period Title: Run-in Period (12 Weeks)
STARTED	2274	0	0
COMPLETED	1748	0	0
NOT COMPLETED	526	0	0
Period Title: Run-in Period (12 Weeks)
STARTED	0	874	874
Treated	0	874	864
Full Analysis Set	0	874	874
Safety Analysis Set	0	874	864
COMPLETED	0	850	831
NOT COMPLETED	0	24	43

Baseline Characteristics

Arm/Group Title	Semaglutide	Insulin Aspart	Total
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.	Total of all reporting groups
Overall Participants	874	874	1748
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.8 (9.4)	61.5 (9.5)	61.2 (9.4)
Sex: Female, Male (Count of Participants)
Female	429 49.1%	425 48.6%	854 48.9%
Male	445 50.9%	449 51.4%	894 51.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 2.6%	22 2.5%	45 2.6%
Not Hispanic or Latino	851 97.4%	852 97.5%	1703 97.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska native	0 0%	0 0%	0 0%
Asian	176 20.1%	166 19%	342 19.6%
Black or African American	21 2.4%	14 1.6%	35 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	674 77.1%	691 79.1%	1365 78.1%
Other	3 0.3%	3 0.3%	6 0.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycated Haemoglobin (HbA1c)
Description	Change from baseline in HbA1c at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	795	783
Mean (Standard Deviation) [Percentage of HbA1c]	-1.5 (1.0)	-1.2 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide, Insulin Aspart
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The responses were analyzed using an ANCOVA with treatment as fixed factor and baseline value as a covariate. Before analysis, missing data were multiple imputed using observed data from participants within the same group defined by randomized treatment, using a regression model including randomized treatment group and data from baseline and all previous visits as covariates. The prespecified non inferiority margin was 0.3%-point.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-distributed test
	Comments	The non-inferiority p-value was calculated as two times the one-sided p-value from a t-distributed test.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to First Event Adjudication Committee (EAC)-Confirmed Severe Hypoglycaemic Episode American Diabetes Association (ADA) From Randomization up to Week 52
Description	First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with plasma glucose (PG) less than or equal to (<=) 3.9 millimoles per liter (mmol/L) (70 milligrams per deciliter (mg/dL)). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) up to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	864
Number [First event per 100 years of exposure]	0.4	0.7

3. Secondary Outcome

Title	Time to First Event Adjudication Committee-confirmed Severe Hypoglycaemic Episode (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening Randomization up to Week 52
Description	First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) up to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	864
Number [First event per 100 years of exposure]	0.2	0.4

4. Secondary Outcome

Title	Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) From Randomization to Week 52
Description	Number of EAC-confirmed severe hypoglycaemic episodes from randomization (week 0) up to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	874
Number [Episodes]	4	7

5. Secondary Outcome

Title	Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose (BG) Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose Less Than (<) 3.1 mmol/L (56 mg/dL)) From Randomization to Week 52
Description	Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <3.1 mmol/L (56 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode, that was BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	874
Number [Episodes]	254	1744

6. Secondary Outcome

Title	Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose <= 3.9 mmol/L (70 mg/dL)) From Randomization to Week 52
Description	Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <=3.9 mmol/L (70 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode during which symptoms of hypoglycaemia were not accompanied by a PG determination but that was presumably caused by a PG concentration <= 3.9 mmol/L (70 mg/dL). Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	874
Number [Episodes]	1420	5616

7. Secondary Outcome

Title	Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening From Randomization to Week 52
Description	Number of EAC-confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life-threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	874
Number [Episodes]	2	4

8. Secondary Outcome

Title	Number of Event Adjudication Committee-confirmed Severe (ADA) or Clinically Significant Hypoglycaemic Episodes (Plasma Glucose < 3.0 mmol/L (54 mg/dL)) From Randomization to Week 52
Description	Number of EAC-confirmed severe or clinically significant hypoglycaemic episodes (plasma glucose < 3.0 mmol/L (54 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Hypoglycaemic episode with plasma glucose < 3.0 mmol/L (54 mg/dL)) was considered as clinically significant. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	From randomization (week 0) to week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	874	874
Number [Episodes]	339	2270

9. Secondary Outcome

Title	Daily Basal Insulin Dose at Week 52
Description	Daily basal insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants exposed to at least one dose of trial product. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	803	794
Mean (Standard Deviation) [Units of insulin]	35.8 (19.4)	40.7 (22.0)

10. Secondary Outcome

Title	Total Daily Insulin Dose at Week 52
Description	Total daily insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants exposed to at least one dose of trial product. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	803	797
Mean (Standard Deviation) [Units of insulin]	35.8 (19.4)	77.7 (40.0)

11. Secondary Outcome

Title	Change From Baseline to Week 52 in Body Weight (Kilogram (kg))
Description	Change from baseline in body weight at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	801	793
Mean (Standard Deviation) [kilograms]	-4.2 (4.6)	2.9 (4.1)

12. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)
Description	Change from baseline in FPG at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	770	762
Mean (Standard Deviation) [millimoles per liter (mmol/L)]	-1.3 (2.9)	-0.8 (3.1)

13. Secondary Outcome

Title	Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile (SMPG ): Mean 7-point Profile (7-PP)
Description	Change from baseline in 7-point self-measured plasma glucose profile: mean 7-PP at week 52 is presented. All participants were instructed to perform 7-point SMPG profiles before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal (dinner), 90 minutes after the start of main evening meal (dinner) and at bedtime. The measurements were to be performed before any injection of bolus insulin and just before the start of the meal (breakfast, lunch or main evening meal), and values measured before breakfast were performed in a fasting condition. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	757	737
Mean (Standard Deviation) [mmol/L]	-2.1 (2.0)	-2.1 (2.0)

14. Secondary Outcome

Title	Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile: Mean Post-prandial Increment (Over All Meals)
Description	Change from baseline in 7-point SMPG profile: mean post-prandial increment (over all meals) at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure .

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	747	724
Mean (Standard Deviation) [mmol/L]	-0.7 (1.8)	-0.9 (2.1)

15. Secondary Outcome

Title	Change From Baseline to Week 52 in Body Mass Index (BMI)
Description	Change from baseline in BMI at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	801	793
Mean (Standard Deviation) [kilograms per meter square (kg/m^2)]	-1.5 (1.7)	1.0 (1.5)

16. Secondary Outcome

Title	Change From Baseline to Week 52 in Waist Circumference
Description	Change from baseline in waist circumference at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	799	793
Mean (Standard Deviation) [centimeters (cm)]	-3.3 (5.6)	2.1 (4.9)

17. Secondary Outcome

Title	Change From Baseline to Week 52 in Body Weight (Percentage): Ratio to Baseline
Description	Change from baseline in body weight (measured in percentage) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	801	793
Mean (Standard Deviation) [Ratio of body weight]	1.0 (0.1)	1.0 (0.0)

18. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Blood Lipids: Total Cholesterol (Ratio to Baseline)
Description	Change from baseline in total cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	792	784
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	1.0 (19.6)	1.0 (20.9)

19. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Blood Lipids: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)
Description	Change from baseline in LDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	789	781
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	1.0 (36.2)	1.0 (35.2)

20. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Blood Lipids: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)
Description	Change from baseline in HDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	751	741
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.0 (16.7)	1.0 (16.4)

21. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Blood Lipids: Triglycerides (Ratio to Baseline)
Description	Change from baseline in triglycerides (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	789	781
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.9 (40.4)	1.0 (42.0)

22. Secondary Outcome

Title	Change From Baseline to Week 52 in Systolic and Diastolic Blood Pressure
Description	Change from baseline in systolic and diastolic blood pressure at week 52 are presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	784	765
Diastolic Blood Pressure	-1.4 (8.7)	-0.4 (9.0)
Systolic Blood Pressure	-2.8 (13.8)	1.0 (14.0)

23. Secondary Outcome

Title	Change From Baseline to Week 52 in Pulse Rate
Description	Change from baseline in pulse rate at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants exposed to at least one dose of trial product. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	784	765
Mean (Standard Deviation) [Beats per minute (beats/min)]	2.2 (8.7)	1.1 (8.7)

24. Secondary Outcome

Title	Change From Baseline to Week 52 in 36-item Short Form Health Survey Version 2 (SF-36v2): Total Summary Scores (Physical Component and Mental Component) and Scores From the 8 Domains
Description	SF-36v2 is 36-item patient-reported survey of patient health to measure participant's overall health-related quality of life (HRQoL). It has 36 items: 8 domains of physical, mental health status (physical functioning, role physical health (range:21.23-57.16), bodily pain (range: 21.68-62.00), general health (range: 18.95-66.50), vitality (range: 22.89-70.42), social functioning (range: 17.23-57.34), role emotional problem (range: 14.39-56.17) and mental health (range: 11.63-63.95)) and 2 total summary scores: physical components summary (range: 7.32-70.14) and mental components summary (range: 5.79-69.91) calculated from domain scores. All 10 scores range from 5.79-70.42 . Higher scores indicated a better health state. Change from baseline in SF-36v2, 2 summary and 8 domains scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from date of first dose of trial product (week 0) to last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	803	794
Physical Component Summary	1.4 (6.4)	0.4 (6.7)
Mental Component Summary	0.1 (8.6)	-0.3 (8.4)
Physical Functioning	1.4 (7.7)	0.2 (7.8)
Role Physical Health	0.1 (7.8)	-0.2 (8.0)
Bodily Pain	1.5 (9.0)	0.8 (9.8)
General Health	1.6 (8.0)	0.3 (8.0)
Vitality	1.1 (8.6)	0.1 (7.9)
Social Functioning	0.2 (9.5)	-0.6 (9.1)
Role Emotional Problem	0.0 (9.4)	-0.2 (9.8)
Mental Health	0.6 (8.7)	0.1 (8.7)

25. Secondary Outcome

Title	Change From Baseline to Week 52 in Diabetes Quality of Life Clinical Trial Questionnaire (DQLCTQ-R): Scores From the 8 Domains
Description	The DQLCTQ-R questionnaire was used to assess participants' HRQoL. The DQLCTQ-R questionnaire contains 57 items and measures and provide scores for the 8 domains (physical function, energy or fatigue, health distress, mental health, satisfaction, treatment satisfaction, treatment flexibility and frequency of symptoms). The 8 domain scores related to DQLCTQ-R are measured on a scale from 0-100. For all scores, higher values indicated better health status. Change from baseline in DQLCTQ-R 8 domain scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).
Time Frame	Baseline (week 0), week 52

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.

Arm/Group Title	Semaglutide	Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.	Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
Measure Participants	802	795
Physical function	2.4 (24.6)	-0.4 (26.4)
Energy or fatigue	2.3 (13.0)	0.4 (12.9)
Health distress	-0.2 (12.4)	0.3 (13.2)
Mental health	7.2 (18.5)	0.5 (20.2)
Satisfaction	4.1 (18.6)	-0.2 (16.2)
Treatment satisfaction	9.9 (23.9)	0.8 (24.4)
Treatment flexibility	4.2 (20.1)	-1.2 (19.8)
Frequency of symptoms	4.1 (15.5)	1.8 (14.7)

Adverse Events

Time Frame	From week 0 to week 52
Adverse Event Reporting Description	All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAEs were defined as AEs with onset during the 'on-treatment' observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product. One participant died after completing end-of-study visit by an ongoing AE which created discrepancies between all cause mortality deaths and participant flow deaths.
Arm/Group Title	Semaglutide		Insulin Aspart
Arm/Group Description	Participants received metformin, IGlar U100 and semaglutide for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast self-measured plasma glucose (SMPG) values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of semaglutide at an initiation dose of 0.25 mg once weekly, after 4 weeks dose was increased to 0.5 mg, and 1 mg after at least 4 weeks to further improve glycaemic control, at investigator's discretion. Dose reduction from 1 to 0.5 mg was allowed in case of safety concern/unacceptable intolerability. Participants were followed up for 5 weeks (week 57) for safety.		Participants received metformin, IGlar U100 and insulin aspart for 52 weeks in treatment period. Metformin dose was maintained at same level and frequency as optimized in run-in period unless safety concern related to background medication arose; IGlar U100 dose was adjusted in run-in period, increases in IGlar U100 dose was based on mean of 3 prebreakfast SMPG values obtained on day of visit/telephone contact and 2 days before contact and dose reduction of IGlar U100 was considered in accordance with approved local label to reduce risk of hypoglycaemia. Participants self-administered s.c. injection of insulin aspart at an initiation dose of 4 units three times daily, dose adjustments were considered twice weekly based on pre-prandial and bedtime SMPG from the preceding 3 days and the individualized goal according to investigator's discretion. Participants were followed up for 5 weeks (week 57) for safety.
All Cause Mortality
	Semaglutide		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/874 (1.4%)		1/864 (0.1%)
Serious Adverse Events
	Semaglutide		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/874 (7.4%)		84/864 (9.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/874 (0%)	0	1/864 (0.1%)	1
Lymphadenitis	1/874 (0.1%)	1	0/864 (0%)	0
Pancytopenia	1/874 (0.1%)	1	0/864 (0%)	0
Cardiac disorders
Acute myocardial infarction	3/874 (0.3%)	4	4/864 (0.5%)	4
Angina pectoris	0/874 (0%)	0	2/864 (0.2%)	2
Angina unstable	1/874 (0.1%)	1	1/864 (0.1%)	1
Aortic valve disease	1/874 (0.1%)	1	0/864 (0%)	0
Aortic valve stenosis	0/874 (0%)	0	2/864 (0.2%)	2
Arteriosclerosis coronary artery	1/874 (0.1%)	1	0/864 (0%)	0
Atrial fibrillation	1/874 (0.1%)	1	3/864 (0.3%)	3
Atrial flutter	1/874 (0.1%)	1	0/864 (0%)	0
Atrioventricular block second degree	0/874 (0%)	0	1/864 (0.1%)	1
Bradyarrhythmia	0/874 (0%)	0	1/864 (0.1%)	1
Cardiac arrest	1/874 (0.1%)	1	0/864 (0%)	0
Cardiac failure	2/874 (0.2%)	2	1/864 (0.1%)	1
Cardiac failure chronic	1/874 (0.1%)	1	1/864 (0.1%)	2
Cardiac failure congestive	0/874 (0%)	0	1/864 (0.1%)	1
Cardiogenic shock	1/874 (0.1%)	1	0/864 (0%)	0
Cardiopulmonary failure	1/874 (0.1%)	1	0/864 (0%)	0
Coronary artery disease	4/874 (0.5%)	4	1/864 (0.1%)	1
Coronary artery occlusion	1/874 (0.1%)	1	0/864 (0%)	0
Coronary artery stenosis	1/874 (0.1%)	1	3/864 (0.3%)	4
Mitral valve incompetence	1/874 (0.1%)	1	0/864 (0%)	0
Myocardial ischaemia	0/874 (0%)	0	1/864 (0.1%)	1
Supraventricular tachycardia	1/874 (0.1%)	1	0/864 (0%)	0
Tachycardia	0/874 (0%)	0	1/864 (0.1%)	1
Ear and labyrinth disorders
Vertigo positional	1/874 (0.1%)	1	0/864 (0%)	0
Endocrine disorders
Goitre	0/874 (0%)	0	1/864 (0.1%)	1
Eye disorders
Cataract	1/874 (0.1%)	1	3/864 (0.3%)	3
Diabetic retinopathy	0/874 (0%)	0	1/864 (0.1%)	1
Macular oedema	0/874 (0%)	0	1/864 (0.1%)	1
Optic ischaemic neuropathy	1/874 (0.1%)	1	0/864 (0%)	0
Gastrointestinal disorders
Abdominal hernia	1/874 (0.1%)	1	0/864 (0%)	0
Anal polyp	1/874 (0.1%)	1	0/864 (0%)	0
Duodenal ulcer haemorrhage	0/874 (0%)	0	1/864 (0.1%)	1
Gastrooesophageal reflux disease	0/874 (0%)	0	1/864 (0.1%)	1
Inguinal hernia	0/874 (0%)	0	1/864 (0.1%)	1
Intestinal obstruction	1/874 (0.1%)	1	0/864 (0%)	0
Pancreatitis acute	0/874 (0%)	0	2/864 (0.2%)	3
General disorders
Adhesion	1/874 (0.1%)	1	0/864 (0%)	0
Chest pain	0/874 (0%)	0	1/864 (0.1%)	1
Death	1/874 (0.1%)	1	0/864 (0%)	0
Impaired healing	1/874 (0.1%)	1	0/864 (0%)	0
Non-cardiac chest pain	0/874 (0%)	0	1/864 (0.1%)	1
Sudden death	1/874 (0.1%)	1	0/864 (0%)	0
Vascular stent stenosis	0/874 (0%)	0	1/864 (0.1%)	1
Hepatobiliary disorders
Jaundice cholestatic	0/874 (0%)	0	1/864 (0.1%)	1
Infections and infestations
Abscess sweat gland	1/874 (0.1%)	1	0/864 (0%)	0
Bronchitis	0/874 (0%)	0	1/864 (0.1%)	1
COVID-19	0/874 (0%)	0	1/864 (0.1%)	1
COVID-19 pneumonia	3/874 (0.3%)	3	2/864 (0.2%)	2
Diabetic gangrene	1/874 (0.1%)	1	0/864 (0%)	0
Empyema	1/874 (0.1%)	1	0/864 (0%)	0
Endocarditis	1/874 (0.1%)	1	0/864 (0%)	0
Gangrene	3/874 (0.3%)	3	0/864 (0%)	0
Gastroenteritis	1/874 (0.1%)	1	1/864 (0.1%)	1
Gastrointestinal viral infection	1/874 (0.1%)	1	0/864 (0%)	0
Infected skin ulcer	1/874 (0.1%)	1	0/864 (0%)	0
Influenza	0/874 (0%)	0	1/864 (0.1%)	1
Lower respiratory tract infection	1/874 (0.1%)	1	1/864 (0.1%)	1
Pneumonia	3/874 (0.3%)	3	5/864 (0.6%)	6
Postoperative wound infection	2/874 (0.2%)	2	0/864 (0%)	0
Pyelonephritis	0/874 (0%)	0	1/864 (0.1%)	1
Pyelonephritis acute	0/874 (0%)	0	1/864 (0.1%)	1
Respiratory tract infection	0/874 (0%)	0	2/864 (0.2%)	2
Staphylococcal sepsis	1/874 (0.1%)	1	0/864 (0%)	0
Streptococcal abscess	1/874 (0.1%)	1	0/864 (0%)	0
Tracheobronchitis	0/874 (0%)	0	1/864 (0.1%)	1
Urinary tract infection	1/874 (0.1%)	1	1/864 (0.1%)	1
Vestibular neuronitis	0/874 (0%)	0	1/864 (0.1%)	1
Wound infection staphylococcal	1/874 (0.1%)	1	0/864 (0%)	0
Injury, poisoning and procedural complications
Electric shock	1/874 (0.1%)	1	0/864 (0%)	0
Fall	1/874 (0.1%)	1	2/864 (0.2%)	2
Femur fracture	0/874 (0%)	0	1/864 (0.1%)	1
Humerus fracture	1/874 (0.1%)	1	0/864 (0%)	0
Joint dislocation	0/874 (0%)	0	1/864 (0.1%)	1
Ligament rupture	0/874 (0%)	0	1/864 (0.1%)	1
Limb injury	0/874 (0%)	0	1/864 (0.1%)	1
Patella fracture	0/874 (0%)	0	1/864 (0.1%)	1
Radius fracture	1/874 (0.1%)	1	1/864 (0.1%)	1
Tendon injury	1/874 (0.1%)	1	1/864 (0.1%)	1
Upper limb fracture	1/874 (0.1%)	1	0/864 (0%)	0
Vascular graft thrombosis	1/874 (0.1%)	1	0/864 (0%)	0
Wrong product administered	0/874 (0%)	0	1/864 (0.1%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/874 (0%)	0	1/864 (0.1%)	1
Diabetic metabolic decompensation	0/874 (0%)	0	1/864 (0.1%)	1
Hyperglycaemia	1/874 (0.1%)	1	0/864 (0%)	0
Hypoglycaemia	1/874 (0.1%)	1	2/864 (0.2%)	2
Hypoglycaemia unawareness	0/874 (0%)	0	1/864 (0.1%)	1
Hypokalaemia	1/874 (0.1%)	1	0/864 (0%)	0
Musculoskeletal and connective tissue disorders
Facet joint syndrome	0/874 (0%)	0	1/864 (0.1%)	1
Osteoarthritis	1/874 (0.1%)	1	1/864 (0.1%)	1
Pain in extremity	0/874 (0%)	0	1/864 (0.1%)	1
Rotator cuff syndrome	0/874 (0%)	0	1/864 (0.1%)	1
Spinal osteoarthritis	0/874 (0%)	0	1/864 (0.1%)	1
Spinal stenosis	1/874 (0.1%)	1	1/864 (0.1%)	2
Spondylolisthesis	0/874 (0%)	0	1/864 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/874 (0.1%)	1	0/864 (0%)	0
Bowen's disease	1/874 (0.1%)	1	0/864 (0%)	0
Glioblastoma	1/874 (0.1%)	1	0/864 (0%)	0
Inflammatory pseudotumour	0/874 (0%)	0	1/864 (0.1%)	1
Intraductal papilloma of breast	0/874 (0%)	0	1/864 (0.1%)	2
Invasive breast carcinoma	0/874 (0%)	0	1/864 (0.1%)	1
Lung adenocarcinoma	1/874 (0.1%)	1	0/864 (0%)	0
Metastases to gastrointestinal tract	1/874 (0.1%)	1	0/864 (0%)	0
Oesophageal squamous cell carcinoma	1/874 (0.1%)	1	0/864 (0%)	0
Ovarian cancer	0/874 (0%)	0	1/864 (0.1%)	1
Pancreatic carcinoma	0/874 (0%)	0	1/864 (0.1%)	1
Pancreatic carcinoma metastatic	0/874 (0%)	0	1/864 (0.1%)	1
Prostate cancer	1/874 (0.1%)	1	0/864 (0%)	0
Rectal neoplasm	0/874 (0%)	0	1/864 (0.1%)	1
Rectosigmoid cancer	0/874 (0%)	0	1/864 (0.1%)	1
Small cell lung cancer metastatic	1/874 (0.1%)	1	0/864 (0%)	0
Transitional cell carcinoma	1/874 (0.1%)	1	0/864 (0%)	0
Transitional cell carcinoma recurrent	0/874 (0%)	0	1/864 (0.1%)	1
Uterine leiomyoma	1/874 (0.1%)	1	0/864 (0%)	0
Vulval cancer	1/874 (0.1%)	1	0/864 (0%)	0
Nervous system disorders
Brain stem infarction	1/874 (0.1%)	1	0/864 (0%)	0
Carotid artery stenosis	1/874 (0.1%)	1	0/864 (0%)	0
Cerebral infarction	0/874 (0%)	0	1/864 (0.1%)	1
Embolic cerebral infarction	0/874 (0%)	0	1/864 (0.1%)	1
Haemorrhagic stroke	1/874 (0.1%)	1	0/864 (0%)	0
Headache	0/874 (0%)	0	1/864 (0.1%)	1
Hypoglycaemic coma	0/874 (0%)	0	1/864 (0.1%)	1
Hypoglycaemic seizure	1/874 (0.1%)	1	0/864 (0%)	0
Hypoglycaemic unconsciousness	0/874 (0%)	0	1/864 (0.1%)	1
Intracranial aneurysm	0/874 (0%)	0	1/864 (0.1%)	1
Ischaemic stroke	2/874 (0.2%)	2	4/864 (0.5%)	4
Loss of consciousness	1/874 (0.1%)	1	0/864 (0%)	0
Syncope	0/874 (0%)	0	1/864 (0.1%)	1
Thalamic infarction	0/874 (0%)	0	1/864 (0.1%)	1
Vertebrobasilar insufficiency	1/874 (0.1%)	1	0/864 (0%)	0
Psychiatric disorders
Delirium	1/874 (0.1%)	2	0/864 (0%)	0
Renal and urinary disorders
Bladder perforation	0/874 (0%)	0	1/864 (0.1%)	1
Nephrolithiasis	3/874 (0.3%)	4	0/864 (0%)	0
Urethral stenosis	0/874 (0%)	0	1/864 (0.1%)	1
Reproductive system and breast disorders
Ovarian cyst	1/874 (0.1%)	1	0/864 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/874 (0%)	0	1/864 (0.1%)	2
Nasal polyps	0/874 (0%)	0	1/864 (0.1%)	1
Pulmonary embolism	1/874 (0.1%)	1	1/864 (0.1%)	1
Pulmonary hypertension	1/874 (0.1%)	1	0/864 (0%)	0
Respiratory failure	0/874 (0%)	0	1/864 (0.1%)	1
Surgical and medical procedures
Hernia repair	0/874 (0%)	0	1/864 (0.1%)	1
Hip arthroplasty	1/874 (0.1%)	1	0/864 (0%)	0
Knee arthroplasty	0/874 (0%)	0	1/864 (0.1%)	1
Removal of internal fixation	0/874 (0%)	0	1/864 (0.1%)	1
Therapeutic procedure	0/874 (0%)	0	1/864 (0.1%)	1
Toe amputation	1/874 (0.1%)	1	0/864 (0%)	0
Vascular disorders
Aortic stenosis	0/874 (0%)	0	1/864 (0.1%)	1
Arteriosclerosis	0/874 (0%)	0	1/864 (0.1%)	1
Peripheral arterial occlusive disease	0/874 (0%)	0	1/864 (0.1%)	1
Peripheral artery occlusion	0/874 (0%)	0	1/864 (0.1%)	1
Peripheral artery stenosis	1/874 (0.1%)	2	1/864 (0.1%)	1
Peripheral ischaemia	0/874 (0%)	0	1/864 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Semaglutide		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	225/874 (25.7%)		65/864 (7.5%)
Gastrointestinal disorders
Diarrhoea	65/874 (7.4%)	98	23/864 (2.7%)	29
Nausea	129/874 (14.8%)	174	7/864 (0.8%)	7
Vomiting	50/874 (5.7%)	78	5/864 (0.6%)	6
Infections and infestations
Nasopharyngitis	57/874 (6.5%)	69	51/864 (5.9%)	73

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.