Multiple Dose Trial Examining Dose Range, Escalation and Efficacy of Oral Semaglutide in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01923181
• Collaborator: (none)
• Enrollment: 632
• Locations: 103
• Arms: 9
• Actual Duration (Months): 12.3
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to examine the dose range, escalation and efficacy of oral semaglutide in subjects with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: semaglutide; Drug: semaglutide; Drug: oral placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 632 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Multiple Dose Trial Examining Dose Range, Escalation and Efficacy of Oral Semaglutide in Subjects With Type 2 Diabetes
• Actual Study Start Date: Dec 2, 2013
• Actual Primary Completion Date: Dec 11, 2014
• Actual Study Completion Date: Dec 11, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1:Semaglutide tablets : 2.5 mg 2.5 mg for 26 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 2:Semaglutide tablets: 2.5 mg/5 mg 2.5 mg for 4 weeks, then 5.0 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 3:Semaglutide tablets: 5.0 mg/10 mg 5.0 mg for 4 weeks, then 10 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 4:Semaglutide tablets:5.0 mg/10 mg/20 mg 5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 5:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg 5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 4 weeks, then 40 mg for 14 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 6:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg 5.0 mg for 8 weeks, then 10 mg for 8 weeks, then 20 mg for 8 weeks, then 40 mg for 2 weeks All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Experimental: 7:Semaglutide tablets: 5.0 mg/10 mg/20 mg/40 mg 5.0 mg for 2 weeks, then 10 mg for 2 weeks, then 20 mg for 2 weeks, then 40 mg for 20 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.
Placebo Comparator: 8:Placebo tablets All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: oral placebo; Once-daily oral administration as tablets.
Active Comparator: 9:Semaglutide injections :0.25 mg/0.50 mg/1.0 mg 0.25 mg for 4 weeks, then 0.50 mg for 4 weeks, then 1.0 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c (Glycosylated Haemoglobin) [Week 0, week 26]

   Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary Outcome Measures

1. Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) [After 26 weeks of treatment]

   Participants who achieved HbA1c <7.0%, was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

2. Change in Body Weight [Week 0, Week 26]

   Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

3. Change in Waist Circumference [Week 0, week 26]

   Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

4. Change in Body Mass Index (BMI) [Week 0, week 26]

   Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

5. Number of Treatment Emergent Adverse Events (TEAEs) Recorded [Weeks 0-31]

   TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

6. Number of Confirmed Hypoglycaemic Episodes Recorded [Weeks 0-31]

   Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• BMI above or equal to 25 and below or equal to 40 kg/m^2

• Subjects diagnosed with T2D (Type 2 diabetes) treated with diet and exercise and/or who have been on a stable dose of metformin for at least 30 days prior to screening

• HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive)

Exclusion Criteria:

• Subjects on selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants

• History of chronic pancreatitis or idiopathic acute pancreatitis

• Chronic malabsorption, regardless of aetiology

• History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease

• Treatment with glucose lowering agent(s) other than metformin as stated in the inclusion criteria in a period of 90 days before the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85712
2	Novo Nordisk Investigational Site	Chula Vista	California	United States	91911
3	Novo Nordisk Investigational Site	Long Beach	California	United States	90806
4	Novo Nordisk Investigational Site	Poway	California	United States	92064
5	Novo Nordisk Investigational Site	Santa Ana	California	United States	92705
6	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
7	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
8	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80904
9	Novo Nordisk Investigational Site	Denver	Colorado	United States	80220
10	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
11	Novo Nordisk Investigational Site	Miami	Florida	United States	33014
12	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
13	Novo Nordisk Investigational Site	South Miami	Florida	United States	33143
14	Novo Nordisk Investigational Site	Athens	Georgia	United States	30606
15	Novo Nordisk Investigational Site	Conyers	Georgia	United States	30094-5965
16	Novo Nordisk Investigational Site	Addison	Illinois	United States	60101
17	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60634
18	Novo Nordisk Investigational Site	Wichita	Kansas	United States	67205
19	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
20	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89103
21	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89109
22	Novo Nordisk Investigational Site	New York	New York	United States	10001
23	Novo Nordisk Investigational Site	New York	New York	United States	10032
24	Novo Nordisk Investigational Site	Rochester	New York	United States	14609
25	Novo Nordisk Investigational Site	Asheville	North Carolina	United States	28801
26	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27609
27	Novo Nordisk Investigational Site	Salisbury	North Carolina	United States	28144
28	Novo Nordisk Investigational Site	Fargo	North Dakota	United States	58104
29	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
30	Novo Nordisk Investigational Site	Jersey Shore	Pennsylvania	United States	17740
31	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19140
32	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19147
33	Novo Nordisk Investigational Site	Moncks Corner	South Carolina	United States	29461
34	Novo Nordisk Investigational Site	Humboldt	Tennessee	United States	38343
35	Novo Nordisk Investigational Site	Spring Hill	Tennessee	United States	37174
36	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
37	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78209
38	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
39	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
40	Novo Nordisk Investigational Site	Wenatchee	Washington	United States	98801-2028
41	Novo Nordisk Investigational Site	Graz		Austria	8036
42	Novo Nordisk Investigational Site	Saint Stefan		Austria	8511
43	Novo Nordisk Investigational Site	Wien		Austria	1010
44	Novo Nordisk Investigational Site	Wien		Austria	1030
45	Novo Nordisk Investigational Site	Wien		Austria	1060
46	Novo Nordisk Investigational Site	Wien		Austria	1130
47	Novo Nordisk Investigational Site	Sofia		Bulgaria	1431
48	Novo Nordisk Investigational Site	Bathurst	New Brunswick	Canada	E2A 4Z9
49	Novo Nordisk Investigational Site	Moncton	New Brunswick	Canada	E1G 1A7
50	Novo Nordisk Investigational Site	Burlington	Ontario	Canada	L7R 1E2
51	Novo Nordisk Investigational Site	Stayner	Ontario	Canada	L0M 1S0
52	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M9W 4L6
53	Novo Nordisk Investigational Site	Pointe-Claire	Quebec	Canada	H9R 3J1
54	Novo Nordisk Investigational Site	Aalborg		Denmark	9100
55	Novo Nordisk Investigational Site	Esbjerg		Denmark	6700
56	Novo Nordisk Investigational Site	Hellerup		Denmark	2900
57	Novo Nordisk Investigational Site	Hillerød		Denmark	3400
58	Novo Nordisk Investigational Site	Svendborg		Denmark	5700
59	Novo Nordisk Investigational Site	Århus C		Denmark	8000
60	Novo Nordisk Investigational Site	Elsterwerda		Germany	04910
61	Novo Nordisk Investigational Site	Falkensee		Germany	14612
62	Novo Nordisk Investigational Site	Friedrichsthal		Germany	66299
63	Novo Nordisk Investigational Site	Hamburg		Germany	22607
64	Novo Nordisk Investigational Site	Münster		Germany	48145
65	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
66	Novo Nordisk Investigational Site	Speyer		Germany	67346
67	Novo Nordisk Investigational Site	Beer Sheva		Israel	84101
68	Novo Nordisk Investigational Site	Haifa		Israel	31096
69	Novo Nordisk Investigational Site	Herzliya		Israel	46851
70	Novo Nordisk Investigational Site	Holon		Israel	58100
71	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
72	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
73	Novo Nordisk Investigational Site	Rishon Le Zion		Israel	75650
74	Novo Nordisk Investigational Site	Milano		Italy	20132
75	Novo Nordisk Investigational Site	Padova		Italy	35128
76	Novo Nordisk Investigational Site	Roma		Italy	00133
77	Novo Nordisk Investigational Site	Roma		Italy	00161
78	Novo Nordisk Investigational Site	Verona		Italy	37126
79	Novo Nordisk Investigational Site	Ipoh		Malaysia	30450
80	Novo Nordisk Investigational Site	Kota Bharu		Malaysia	15586
81	Novo Nordisk Investigational Site	Penang		Malaysia	10450
82	Novo Nordisk Investigational Site	Seri Manjung		Malaysia	32040
83	Novo Nordisk Investigational Site	Belgrade		Serbia	11000
84	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6045
85	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1829
86	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2090
87	Novo Nordisk Investigational Site	Almería		Spain	04001
88	Novo Nordisk Investigational Site	Sabadell		Spain	08208
89	Novo Nordisk Investigational Site	Sevilla		Spain	41003
90	Novo Nordisk Investigational Site	Sevilla		Spain	41010
91	Novo Nordisk Investigational Site	Valencia		Spain	46026
92	Novo Nordisk Investigational Site	Karlstad		Sweden	651 85
93	Novo Nordisk Investigational Site	Linköping		Sweden	582 16
94	Novo Nordisk Investigational Site	Oskarshamn		Sweden	572 28
95	Novo Nordisk Investigational Site	Örebro		Sweden	701 85
96	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT16 1RH
97	Novo Nordisk Investigational Site	Bexhill-on-Sea		United Kingdom	TN39 4SP
98	Novo Nordisk Investigational Site	Chesterfield, Derbyshire		United Kingdom	S40 4AA
99	Novo Nordisk Investigational Site	Chester		United Kingdom	CH2 1UL
100	Novo Nordisk Investigational Site	Crewe		United Kingdom	CW5 5NX
101	Novo Nordisk Investigational Site	Hinckley		United Kingdom	LE10 2SE
102	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE5 4PW
103	Novo Nordisk Investigational Site	London		United Kingdom	W6 7HY

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2016
• Statistical Analysis Plan - Jul 1, 2015

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01923181
• Other Study ID Numbers: NN9924-3790; 2012-004994-16; U1111-1136-4716
• First Posted: Aug 15, 2013
• Last Update Posted: Jan 15, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 100 sites in 14 countries as follows: Austria (6), Bulgaria (3), Canada (6), Denmark (6), Germany (6), Israel (6), Italy (4), Malaysia (4), Serbia (1), South Africa (3), Spain (5), Sweden (3), United Kingdom (8) and United States (39).
Pre-assignment Detail	Data presented in "participant flow" is based on the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Period Title: Overall Study
STARTED	70	70	69	70	71	70	70	69	71
Full Analysis Set (FAS)	70	70	69	70	71	70	70	69	71
Safety Analysis Set (SAS)	70	70	69	70	71	70	70	69	71
COMPLETED	67	64	67	65	63	66	62	61	68
NOT COMPLETED	3	6	2	5	8	4	8	8	3

Baseline Characteristics

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo	Total
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.	Total of all reporting groups
Overall Participants	70	70	69	70	71	70	70	69	71	630
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (9.9)	55.7 (11.0)	56.5 (10.1)	58.3 (10.4)	56.5 (10.2)	57.1 (10.5)	57.7 (10.8)	56.8 (11.8)	58.9 (10.3)	57.1 (10.6)
Sex: Female, Male (Count of Participants)
Female	25 35.7%	23 32.9%	26 37.7%	26 37.1%	28 39.4%	29 41.4%	26 37.1%	21 30.4%	31 43.7%	235 37.3%
Male	45 64.3%	47 67.1%	43 62.3%	44 62.9%	43 60.6%	41 58.6%	44 62.9%	48 69.6%	40 56.3%	395 62.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 8.6%	7 10%	7 10.1%	7 10%	7 9.9%	9 12.9%	12 17.1%	7 10.1%	9 12.7%	71 11.3%
Not Hispanic or Latino	64 91.4%	63 90%	62 89.9%	63 90%	64 90.1%	61 87.1%	58 82.9%	62 89.9%	62 87.3%	559 88.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	57 81.4%	63 90%	57 82.6%	59 84.3%	63 88.7%	54 77.1%	59 84.3%	54 78.3%	57 80.3%	523 83%
Black or African American	6 8.6%	2 2.9%	7 10.1%	4 5.7%	4 5.6%	7 10%	7 10%	4 5.8%	6 8.5%	47 7.5%
Asian	7 10%	4 5.7%	4 5.8%	4 5.7%	3 4.2%	7 10%	4 5.7%	10 14.5%	7 9.9%	50 7.9%
American Indian or Alaska Native	0 0%	0 0%	0 0%	2 2.9%	0 0%	0 0%	0 0%	0 0%	1 1.4%	3 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Other	0 0%	1 1.4%	1 1.4%	1 1.4%	1 1.4%	2 2.9%	0 0%	1 1.4%	0 0%	7 1.1%
Glycosylated haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	7.99 (0.72)	7.80 (0.62)	7.80 (0.70)	7.86 (0.69)	8.05 (0.75)	7.96 (0.73)	7.77 (0.75)	7.77 (0.71)	8.00 (0.80)	7.89 (0.73)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c (Glycosylated Haemoglobin)
Description	Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Oral Semaglutide 40 mg Pooled	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	The data from participants in oral semaglutide 40 mg arm and oral semaglutide fast dose-escalation arm were pooled in this arm.	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	56	58	57	48	46	52	44	90	48	51
Mean (Standard Deviation) [Percentage of HbA1c]	-0.88 (0.77)	-1.23 (0.79)	-1.56 (0.92)	-1.70 (0.75)	-2.04 (0.90)	-1.76 (0.92)	-1.65 (0.77)	-1.85 (0.86)	-1.85 (0.75)	-0.40 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Pooled, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-1.47
	Confidence Interval	(2-Sided) 95%; -1.73 to -1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg pooled - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 2.5 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.69 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 2.5 mg - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 5 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -1.18 to -0.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 5 mg - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 10 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.18
	Confidence Interval	(2-Sided) 95%; -1.47 to -0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 10 mg - Placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 20 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 95%; -1.68 to -1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral Semaglutide 20 mg - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -1.89 to -1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg - Placebo

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Slow Dose-escalation, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.43
	Confidence Interval	(2-Sided) 95%; -1.72 to -1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg slow dose-escalation - Placebo

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Fast Dose-escalation, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.34
	Confidence Interval	(2-Sided) 95%; -1.64 to -1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg fast dose-escalation - Placebo

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous Semaglutide 1 mg, Placebo
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.56
	Confidence Interval	(2-Sided) 95%; -1.85 to -1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Subcutaneous semaglutide 1 mg - Placebo

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 2.5 mg, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 2.5 mg - Subcutaneous semaglutide 1 mg

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 5 mg, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 5 mg - Subcutaneous semaglutide 1 mg

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 10 mg, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.0116
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 10 mg - Subcutaneous semaglutide 1 mg

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 20 mg, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.2440
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 20 mg - Subcutaneous semaglutide 1 mg

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.7973
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg - Subcutaneous semaglutide 1 mg

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Slow Dose-escalation, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.3901
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg slow-dose escalation - Subcutaneous semaglutide 1 mg

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Fast Dose-escalation, Subcutaneous Semaglutide 1 mg
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.1612
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg fast-dose escalation - Subcutaneous semaglutide 1 mg

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg, Oral Semaglutide 40 mg Slow Dose-escalation
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.2669
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg slow-dose escalation - Oral semaglutide 40 mg

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg, Oral Semaglutide 40 mg Fast Dose-escalation
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.0989
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg fast-dose escalation - Oral semaglutide 40 mg

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 40 mg Slow Dose-escalation, Oral Semaglutide 40 mg Fast Dose-escalation
	Comments	Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	0.5565
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 40 mg fast-dose escalation - Oral semaglutide 40 mg slow-dose escalation

2. Secondary Outcome

Title	Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol)
Description	Participants who achieved HbA1c <7.0%, was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	After 26 weeks of treatment

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	56	58	57	48	46	52	44	48	51
Yes	27 38.6%	50 71.4%	49 71%	41 58.6%	42 59.2%	47 67.1%	38 54.3%	45 65.2%	18 25.4%
No	29 41.4%	8 11.4%	8 11.6%	7 10%	4 5.6%	5 7.1%	6 8.6%	3 4.3%	33 46.5%

3. Secondary Outcome

Title	Change in Body Weight
Description	Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	56	57	57	47	46	51	44	46	51
Mean (Standard Deviation) [kg]	-2.01 (3.08)	-2.89 (3.32)	-4.90 (4.04)	-5.75 (5.63)	-6.91 (4.57)	-5.93 (4.34)	-8.29 (5.27)	-6.71 (3.18)	-1.16 (2.59)

4. Secondary Outcome

Title	Change in Waist Circumference
Description	Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	56	56	57	47	46	51	44	46	51
Mean (Standard Deviation) [cm]	-2.00 (4.31)	-2.29 (4.54)	-5.28 (5.55)	-4.08 (4.01)	-5.71 (4.65)	-4.86 (5.48)	-6.24 (4.71)	-6.34 (4.65)	-2.29 (3.99)

5. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	56	57	57	47	46	51	44	46	51
Mean (Standard Deviation) [kg/m^2]	-0.67 (0.98)	-0.98 (1.14)	-1.72 (1.44)	-1.93 (1.87)	-2.37 (1.58)	-2.04 (1.45)	-2.92 (1.93)	-2.32 (1.04)	-0.43 (0.94)

6. Secondary Outcome

Title	Number of Treatment Emergent Adverse Events (TEAEs) Recorded
Description	TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Weeks 0-31

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = safety analysis set (SAS) which comprised all participants exposed to at least 1 dose of randomised semaglutide or placebo.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	70	70	69	70	71	70	70	69	71
Number [Events]	142	169	233	289	230	233	245	218	127

7. Secondary Outcome

Title	Number of Confirmed Hypoglycaemic Episodes Recorded
Description	Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia.
Time Frame	Weeks 0-31

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all participants exposed to at least 1 dose of randomised semaglutide or placebo.

Arm/Group Title	Oral Semaglutide 2.5 mg	Oral Semaglutide 5 mg	Oral Semaglutide 10 mg	Oral Semaglutide 20 mg	Oral Semaglutide 40 mg	Oral Semaglutide 40 mg Slow Dose-escalation	Oral Semaglutide 40 mg Fast Dose-escalation	Subcutaneous Semaglutide 1 mg	Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets	Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.	Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
Measure Participants	70	70	69	70	71	70	70	69	71
Number [Episodes]	4	4	6	1	1	3	1	6	5

Adverse Events

Time Frame	Week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product.
Adverse Event Reporting Description	Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Arm/Group Title	Oral Semaglutide 2.5 mg		Oral Semaglutide 5 mg		Oral Semaglutide 10 mg		Oral Semaglutide 20 mg		Oral Semaglutide 40 mg		Oral Semaglutide 40 mg Slow Dose-escalation		Oral Semaglutide 40 mg Fast Dose-escalation		Subcutaneous Semaglutide 1 mg		Placebo
Arm/Group Description	Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets		Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals.		Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets.
All Cause Mortality
	Oral Semaglutide 2.5 mg		Oral Semaglutide 5 mg		Oral Semaglutide 10 mg		Oral Semaglutide 20 mg		Oral Semaglutide 40 mg		Oral Semaglutide 40 mg Slow Dose-escalation		Oral Semaglutide 40 mg Fast Dose-escalation		Subcutaneous Semaglutide 1 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/70 (0%)		0/69 (0%)		0/70 (0%)		0/71 (0%)		0/70 (0%)		0/70 (0%)		0/69 (0%)		0/71 (0%)
Serious Adverse Events
	Oral Semaglutide 2.5 mg		Oral Semaglutide 5 mg		Oral Semaglutide 10 mg		Oral Semaglutide 20 mg		Oral Semaglutide 40 mg		Oral Semaglutide 40 mg Slow Dose-escalation		Oral Semaglutide 40 mg Fast Dose-escalation		Subcutaneous Semaglutide 1 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/70 (1.4%)		2/70 (2.9%)		2/69 (2.9%)		0/70 (0%)		1/71 (1.4%)		3/70 (4.3%)		5/70 (7.1%)		2/69 (2.9%)		5/71 (7%)
Cardiac disorders
Supraventricular tachycardia	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	2
Eye disorders
Pterygium	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Diverticulum intestinal	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Nausea	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Vomiting	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
General disorders
Non-cardiac chest pain	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	1/70 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Infections and infestations
Appendicitis	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	1/71 (1.4%)	1	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Gastroenteritis	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Groin abscess	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Joint abscess	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	1/70 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Pneumonia	1/70 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Injury, poisoning and procedural complications
Arthropod sting	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Postoperative adhesion	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	2	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Investigations
Pancreatic enzymes increased	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Hypoglycaemia	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Rhabdomyolysis	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal neoplasm	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Nervous system disorders
Cerebral infarction	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Transient ischaemic attack	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	1/70 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Renal and urinary disorders
Calculus ureteric	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Renal failure acute	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/70 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Other (Not Including Serious) Adverse Events
	Oral Semaglutide 2.5 mg		Oral Semaglutide 5 mg		Oral Semaglutide 10 mg		Oral Semaglutide 20 mg		Oral Semaglutide 40 mg		Oral Semaglutide 40 mg Slow Dose-escalation		Oral Semaglutide 40 mg Fast Dose-escalation		Subcutaneous Semaglutide 1 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/70 (50%)		32/70 (45.7%)		37/69 (53.6%)		49/70 (70%)		49/71 (69%)		42/70 (60%)		55/70 (78.6%)		44/69 (63.8%)		34/71 (47.9%)
Gastrointestinal disorders
Abdominal discomfort	0/70 (0%)	0	1/70 (1.4%)	1	2/69 (2.9%)	2	3/70 (4.3%)	3	2/71 (2.8%)	2	1/70 (1.4%)	1	4/70 (5.7%)	5	5/69 (7.2%)	7	0/71 (0%)	0
Abdominal distension	0/70 (0%)	0	3/70 (4.3%)	3	1/69 (1.4%)	1	2/70 (2.9%)	2	6/71 (8.5%)	6	1/70 (1.4%)	1	3/70 (4.3%)	3	3/69 (4.3%)	4	5/71 (7%)	5
Abdominal pain	3/70 (4.3%)	3	1/70 (1.4%)	1	1/69 (1.4%)	1	5/70 (7.1%)	8	3/71 (4.2%)	3	4/70 (5.7%)	4	3/70 (4.3%)	3	4/69 (5.8%)	4	0/71 (0%)	0
Abdominal pain upper	0/70 (0%)	0	2/70 (2.9%)	2	1/69 (1.4%)	1	6/70 (8.6%)	8	2/71 (2.8%)	2	4/70 (5.7%)	6	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Constipation	4/70 (5.7%)	4	4/70 (5.7%)	4	6/69 (8.7%)	8	5/70 (7.1%)	8	9/71 (12.7%)	11	7/70 (10%)	7	8/70 (11.4%)	9	7/69 (10.1%)	7	4/71 (5.6%)	5
Diarrhoea	5/70 (7.1%)	6	7/70 (10%)	7	16/69 (23.2%)	20	14/70 (20%)	18	10/71 (14.1%)	15	14/70 (20%)	27	12/70 (17.1%)	15	10/69 (14.5%)	14	7/71 (9.9%)	10
Dyspepsia	2/70 (2.9%)	6	5/70 (7.1%)	7	6/69 (8.7%)	6	8/70 (11.4%)	8	6/71 (8.5%)	8	6/70 (8.6%)	8	5/70 (7.1%)	5	10/69 (14.5%)	11	3/71 (4.2%)	3
Eructation	0/70 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	2/70 (2.9%)	2	5/71 (7%)	5	1/70 (1.4%)	1	2/70 (2.9%)	2	2/69 (2.9%)	2	0/71 (0%)	0
Gastrooesophageal reflux disease	2/70 (2.9%)	2	2/70 (2.9%)	2	4/69 (5.8%)	4	5/70 (7.1%)	7	4/71 (5.6%)	4	4/70 (5.7%)	4	4/70 (5.7%)	4	1/69 (1.4%)	1	1/71 (1.4%)	1
Nausea	9/70 (12.9%)	12	10/70 (14.3%)	13	23/69 (33.3%)	27	25/70 (35.7%)	37	24/71 (33.8%)	37	23/70 (32.9%)	29	25/70 (35.7%)	27	22/69 (31.9%)	23	1/71 (1.4%)	1
Vomiting	4/70 (5.7%)	8	4/70 (5.7%)	5	14/69 (20.3%)	18	12/70 (17.1%)	15	14/71 (19.7%)	25	11/70 (15.7%)	22	16/70 (22.9%)	20	6/69 (8.7%)	6	3/71 (4.2%)	3
General disorders
Fatigue	3/70 (4.3%)	3	3/70 (4.3%)	3	3/69 (4.3%)	3	5/70 (7.1%)	6	1/71 (1.4%)	1	1/70 (1.4%)	1	3/70 (4.3%)	3	2/69 (2.9%)	3	2/71 (2.8%)	2
Infections and infestations
Gastroenteritis	1/70 (1.4%)	1	0/70 (0%)	0	2/69 (2.9%)	3	2/70 (2.9%)	2	2/71 (2.8%)	2	2/70 (2.9%)	2	4/70 (5.7%)	6	2/69 (2.9%)	2	0/71 (0%)	0
Influenza	2/70 (2.9%)	2	0/70 (0%)	0	3/69 (4.3%)	5	3/70 (4.3%)	4	2/71 (2.8%)	2	1/70 (1.4%)	1	1/70 (1.4%)	1	1/69 (1.4%)	1	5/71 (7%)	7
Nasopharyngitis	6/70 (8.6%)	7	3/70 (4.3%)	4	3/69 (4.3%)	3	5/70 (7.1%)	6	5/71 (7%)	5	3/70 (4.3%)	4	4/70 (5.7%)	5	2/69 (2.9%)	3	9/71 (12.7%)	9
Upper respiratory tract infection	3/70 (4.3%)	3	4/70 (5.7%)	5	1/69 (1.4%)	1	6/70 (8.6%)	7	1/71 (1.4%)	1	2/70 (2.9%)	2	0/70 (0%)	0	4/69 (5.8%)	4	1/71 (1.4%)	1
Investigations
Lipase increased	2/70 (2.9%)	2	1/70 (1.4%)	1	1/69 (1.4%)	1	3/70 (4.3%)	3	3/71 (4.2%)	3	4/70 (5.7%)	4	4/70 (5.7%)	4	3/69 (4.3%)	3	2/71 (2.8%)	2
Weight decreased	0/70 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	2/70 (2.9%)	2	4/71 (5.6%)	4	0/70 (0%)	0	3/70 (4.3%)	3	1/69 (1.4%)	1	0/71 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/70 (4.3%)	4	2/70 (2.9%)	2	10/69 (14.5%)	10	8/70 (11.4%)	8	10/71 (14.1%)	11	3/70 (4.3%)	4	11/70 (15.7%)	11	9/69 (13%)	9	1/71 (1.4%)	1
Nervous system disorders
Dizziness	5/70 (7.1%)	5	3/70 (4.3%)	3	3/69 (4.3%)	3	3/70 (4.3%)	3	4/71 (5.6%)	4	0/70 (0%)	0	5/70 (7.1%)	5	2/69 (2.9%)	2	0/71 (0%)	0
Headache	4/70 (5.7%)	6	9/70 (12.9%)	9	8/69 (11.6%)	10	10/70 (14.3%)	18	4/71 (5.6%)	7	8/70 (11.4%)	10	7/70 (10%)	7	10/69 (14.5%)	21	4/71 (5.6%)	4
Respiratory, thoracic and mediastinal disorders
Cough	2/70 (2.9%)	2	2/70 (2.9%)	2	4/69 (5.8%)	4	1/70 (1.4%)	1	0/71 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	2	3/69 (4.3%)	3	1/71 (1.4%)	1
Vascular disorders
Hypertension	4/70 (5.7%)	4	3/70 (4.3%)	3	2/69 (2.9%)	2	6/70 (8.6%)	6	1/71 (1.4%)	1	2/70 (2.9%)	2	2/70 (2.9%)	2	3/69 (4.3%)	3	1/71 (1.4%)	1

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