SUSTAIN™ 2: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01930188
• Collaborator: (none)
• Enrollment: 1,231
• Locations: 141
• Arms: 4
• Actual Duration (Months): 22.3
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This trial is conducted in Africa, Asia, Europe and South America. The aim of the trial is to evaluate efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin and/or TZD (thiazolidinedione) in subjects with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: semaglutide; Drug: sitagliptin; Drug: placebo; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1231 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes (SUSTAIN™ 2 - vs. DPP-4 Inhibitor)
• Actual Study Start Date: Dec 2, 2013
• Actual Primary Completion Date: Oct 12, 2015
• Actual Study Completion Date: Oct 12, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide 0.5 mg + sitagliptin placebo	Drug: semaglutide; For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.; Drug: placebo; Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
Experimental: Semaglutide 1.0 mg + sitagliptin placebo	Drug: semaglutide; For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.; Drug: placebo; Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.
Active Comparator: Sitagliptin 100 mg + semaglutide placebo 1.0 mg	Drug: sitagliptin; Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.; Drug: placebo; For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.
Active Comparator: Sitagliptin 100 mg + semaglutide placebo 0.5 mg	Drug: sitagliptin; Tablets for oral administration once daily. The trial drug will be added on to the subject's stable pre-trial medication.; Drug: placebo; For subcutaneous injection (s.c., under the skin) once weekly. Will follow a fixed dose escalation regimen. The trial drug will be added on to the subject's stable pre-trial medication.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c (Glycosylated Haemoglobin) From Baseline [Week 0, week 56]

   Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.

Secondary Outcome Measures

1. Change in Body Weight From Baseline [Week 0, week 56]

   Change in body weight from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.

2. Change in Fasting Plasma Glucose (FPG) From Baseline [Week 0, week 56]

   Change in fasting plasma glucose from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.

3. Change in Systolic and Diastolic Blood Pressure From Baseline [Week 0, week 56]

   Change in systolic and diastolic blood pressure from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin

4. Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline [Week 0, week 56]

   Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin. The DTSQs questionnaire was used to assess subjects' treatment satisfaction. This questionnaire contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction.

5. Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no) [After 56 weeks treatment]

   Subjects who achieved HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target (yes/no) after week 56 weeks of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Japan: Age minimum 20 years - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 90 days prior to screening with either metformin above or equal to 1500 mg (or maximum tolerated dose), pioglitazone above or equal to 30 mg (or maximum tolerated dose), rosiglitazone above or equal to 4 mg (or maximum tolerated dose) or a combination of either metformin/pioglitazone or metformin/rosiglitazone (doses as for individual therapies). Stable is defined as unchanged medication and unchanged dose

• HbA1c 7.0 - 10.5 % (53 - 91 mmol/mol) (both inclusive) Exclusion Criteria: - Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local law or practice) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Buenos Aires		Argentina	C1425AGC
2	Novo Nordisk Investigational Site	Caba		Argentina	C1179AAB
3	Novo Nordisk Investigational Site	Caba		Argentina
4	Novo Nordisk Investigational Site	Mar del Plata		Argentina	B7600GNY
5	Novo Nordisk Investigational Site	Burgas		Bulgaria	8000
6	Novo Nordisk Investigational Site	Haskovo		Bulgaria	6300
7	Novo Nordisk Investigational Site	Petrich		Bulgaria	2850
8	Novo Nordisk Investigational Site	Ruse		Bulgaria	7000
9	Novo Nordisk Investigational Site	Sliven		Bulgaria	8800
10	Novo Nordisk Investigational Site	Smolyan		Bulgaria	4700
11	Novo Nordisk Investigational Site	Sofia		Bulgaria	1233
12	Novo Nordisk Investigational Site	Sofia		Bulgaria	1336
13	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6000
14	Novo Nordisk Investigational Site	Vratsa		Bulgaria	3001
15	Novo Nordisk Investigational Site	Chrudim		Czechia	537 01
16	Novo Nordisk Investigational Site	Ostrava		Czechia	707 02
17	Novo Nordisk Investigational Site	Plzen		Czechia	304 60
18	Novo Nordisk Investigational Site	Praha 4- Chodov		Czechia	149 00
19	Novo Nordisk Investigational Site	Praha 5		Czechia	150 00
20	Novo Nordisk Investigational Site	Shatin, New Territories		Hong Kong
21	Novo Nordisk Investigational Site	Budapest		Hungary	1076
22	Novo Nordisk Investigational Site	Budapest		Hungary	H-1134
23	Novo Nordisk Investigational Site	Debrecen		Hungary	4043
24	Novo Nordisk Investigational Site	Szeged		Hungary	H-6720
25	Novo Nordisk Investigational Site	Szombathely		Hungary	H-9700
26	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500003
27	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380006
28	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560034
29	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560054
30	Novo Nordisk Investigational Site	Kochi	Kerala	India	682041
31	Novo Nordisk Investigational Site	Kozhikode	Kerala	India	673017
32	Novo Nordisk Investigational Site	Trivandrum	Kerala	India	695011
33	Novo Nordisk Investigational Site	Indore	Madhya Pradesh	India	452010
34	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
35	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411001
36	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411004
37	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411040
38	Novo Nordisk Investigational Site	Bhubaneswar	Orissa	India	751019
39	Novo Nordisk Investigational Site	Ludhiana	Punjab	India	141001
40	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302004
41	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600116
42	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700020
43	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
44	Novo Nordisk Investigational Site	New Delhi		India	110017
45	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido		Japan	070-0002
46	Novo Nordisk Investigational Site	Ibaraki		Japan	311-0113
47	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka		Japan	582-0005
48	Novo Nordisk Investigational Site	Kitakyushu-shi, Fukuoka		Japan	800 0252
49	Novo Nordisk Investigational Site	Mitaka-shi, Tokyo		Japan	181-0013
50	Novo Nordisk Investigational Site	Mito-shi, Ibaraki		Japan	310-0826
51	Novo Nordisk Investigational Site	Miyazaki		Japan	880-0034
52	Novo Nordisk Investigational Site	Okayama-shi, Okayama		Japan	700 8505
53	Novo Nordisk Investigational Site	Osaka-shi, Osaka		Japan	532 0003
54	Novo Nordisk Investigational Site	Osaka-shi, Osaka		Japan
55	Novo Nordisk Investigational Site	Osaka		Japan	569-1045
56	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido		Japan	060-0001
57	Novo Nordisk Investigational Site	Tokyo		Japan	103-0027
58	Novo Nordisk Investigational Site	Tokyo		Japan	125-0054
59	Novo Nordisk Investigational Site	Pachuca	Hidalgo	Mexico	42084
60	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44670
61	Novo Nordisk Investigational Site	Monterrey	Nuevo León	Mexico	64620
62	Novo Nordisk Investigational Site	Aguascalientes		Mexico	20129
63	Novo Nordisk Investigational Site	Aguascalientes		Mexico	20230
64	Novo Nordisk Investigational Site	Hamar		Norway	2317
65	Novo Nordisk Investigational Site	Kløfta		Norway	2040
66	Novo Nordisk Investigational Site	Kongsvinger		Norway	2212
67	Novo Nordisk Investigational Site	Stavanger		Norway	4005
68	Novo Nordisk Investigational Site	Ålesund		Norway	6003
69	Novo Nordisk Investigational Site	Almada		Portugal	2805-267
70	Novo Nordisk Investigational Site	Coimbra		Portugal	3046-853
71	Novo Nordisk Investigational Site	Lisboa		Portugal	1250-230
72	Novo Nordisk Investigational Site	Lisboa		Portugal	1500-650
73	Novo Nordisk Investigational Site	Matosinhos		Portugal	4464-513
74	Novo Nordisk Investigational Site	Tomar		Portugal	2304-909
75	Novo Nordisk Investigational Site	Viana do Castelo		Portugal	4901-858
76	Novo Nordisk Investigational Site	Vila Nova de Gaia		Portugal	4434-502
77	Novo Nordisk Investigational Site	Baia Mare	Maramures	Romania	430123
78	Novo Nordisk Investigational Site	Ploiesti	Prahova	Romania	100342
79	Novo Nordisk Investigational Site	Brasov		Romania	500365
80	Novo Nordisk Investigational Site	Bucharest		Romania	020359
81	Novo Nordisk Investigational Site	Bucharest		Romania	022441
82	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656024
83	Novo Nordisk Investigational Site	Moscow		Russian Federation	115478
84	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
85	Novo Nordisk Investigational Site	Moscow		Russian Federation	119435
86	Novo Nordisk Investigational Site	Moscow		Russian Federation	125367
87	Novo Nordisk Investigational Site	Moscow		Russian Federation
88	Novo Nordisk Investigational Site	Nizhniy Novgorod		Russian Federation	603011
89	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630047
90	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630099
91	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	197762
92	Novo Nordisk Investigational Site	Samara		Russian Federation	443041
93	Novo Nordisk Investigational Site	Saratov		Russian Federation	410018
94	Novo Nordisk Investigational Site	Smolensk		Russian Federation	214019
95	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634063
96	Novo Nordisk Investigational Site	Tumen		Russian Federation	625023
97	Novo Nordisk Investigational Site	Ufa		Russian Federation	450083
98	Novo Nordisk Investigational Site	Volgograd		Russian Federation	400138
99	Novo Nordisk Investigational Site	Voronezh		Russian Federation	394018
100	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150003
101	Novo Nordisk Investigational Site	East London	Eastern Cape	South Africa	5201
102	Novo Nordisk Investigational Site	Bloemfontein	Free State	South Africa	9301
103	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2001
104	Novo Nordisk Investigational Site	Krugersdorp	Gauteng	South Africa	1739
105	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0002
106	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0084
107	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4001
108	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4092
109	Novo Nordisk Investigational Site	Almería		Spain	04001
110	Novo Nordisk Investigational Site	Centelles (Barcelona)		Spain	08540
111	Novo Nordisk Investigational Site	La Coruña		Spain	15006
112	Novo Nordisk Investigational Site	La Roca del Vallés		Spain	08430
113	Novo Nordisk Investigational Site	Lleida		Spain	25198
114	Novo Nordisk Investigational Site	Palma de Mallorca		Spain	07010
115	Novo Nordisk Investigational Site	Sevilla		Spain	41003
116	Novo Nordisk Investigational Site	Kristianstad		Sweden	291 85
117	Novo Nordisk Investigational Site	Lund		Sweden	222 22
118	Novo Nordisk Investigational Site	Malmö		Sweden	205 02
119	Novo Nordisk Investigational Site	Stockholm		Sweden	113 24
120	Novo Nordisk Investigational Site	Bangkoknoi, Bangkok		Thailand	10700
121	Novo Nordisk Investigational Site	Bangkok		Thailand	10330
122	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
123	Novo Nordisk Investigational Site	Nakhon Ratchasima		Thailand	30000
124	Novo Nordisk Investigational Site	Ankara		Turkey	06110
125	Novo Nordisk Investigational Site	Antalya		Turkey	07058
126	Novo Nordisk Investigational Site	Istanbul		Turkey	34303
127	Novo Nordisk Investigational Site	Istanbul		Turkey	34371
128	Novo Nordisk Investigational Site	Istanbul		Turkey	34718
129	Novo Nordisk Investigational Site	Istanbul		Turkey	34722
130	Novo Nordisk Investigational Site	Istanbul		Turkey	34752
131	Novo Nordisk Investigational Site	Istanbul		Turkey	34890
132	Novo Nordisk Investigational Site	Konya		Turkey	42090
133	Novo Nordisk Investigational Site	Rize		Turkey	53020
134	Novo Nordisk Investigational Site	Trabzon		Turkey	61040
135	Novo Nordisk Investigational Site	Çorum		Turkey	19200
136	Novo Nordisk Investigational Site	Cherkasy		Ukraine	18009
137	Novo Nordisk Investigational Site	Ivano-Frankivsk		Ukraine	76018
138	Novo Nordisk Investigational Site	Kyiv		Ukraine	04114
139	Novo Nordisk Investigational Site	Odesa		Ukraine	65114
140	Novo Nordisk Investigational Site	Vinnytsia		Ukraine	21010
141	Novo Nordisk Investigational Site	Zaporizhia		Ukraine	69600

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Fonseca VA, Capehorn MS, Garg SK, Jódar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in insulin resistance are mediated primarily via weight loss in subjects with type 2 diabetes on semaglutide. J Clin Endocrinol Metab. 2019 Apr 2. pii: jc.2018-02685. doi: 10.1210/jc.2018-02685. [Epub ahead of print] Erratum in: J Clin Endocrinol Metab. 2020 Jan 1;105(1):.
• Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA(1C) ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01930188
• Other Study ID Numbers: NN9535-3626; 2012-004827-19; U1111-1135-8730; 132366; CTRI/2014/05/004626
• First Posted: Aug 28, 2013
• Last Update Posted: Jun 13, 2019
• Last Verified: May 1, 2019

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

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 124 sites in 18 countries: Argentina: 4; Bulgaria: 10; Czech Republic: 5; Hong Kong: 1; Hungary: 4; India: 11; Japan: 14; Mexico: 5 Norway: 5; Portugal: 6; Romania: 5; Russian Federation: 17; South Africa: 7; Spain: 7: Sweden: 4; Thailand: 4; Turkey: 9; and Ukraine: 6 sites.

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Period Title: Overall Study
STARTED	409	409	407
Premature Discontinuation of Treatment	53	61	32
COMPLETED	387	388	388
NOT COMPLETED	22	21	19

Baseline Characteristics

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo	Total
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.	Total of all reporting groups
Overall Participants	409	409	407	1225
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (10.2)	56.0 (9.4)	54.6 (10.4)	55.1 (10.0)
Sex: Female, Male (Count of Participants)
Female	202 49.4%	204 49.9%	199 48.9%	605 49.4%
Male	207 50.6%	205 50.1%	208 51.1%	620 50.6%
HbA1c (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	8.01 (0.92)	8.04 (0.93)	8.17 (0.92)	8.07 (0.93)
Body Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	89.93 (20.39)	89.21 (20.74)	89.29 (19.67)	89.48 (20.26)
Fasting Plasma Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.33 (2.38)	9.29 (2.22)	9.60 (2.16)	9.40 (2.26)
Diastolic and Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Diastolic Blood pressure	80.63 (9.76)	80.87 (9.08)	80.48 (8.70)	80.66 (9.19)
Systolic Blood pressure	132.73 (16.09)	132.56 (13.93)	132.66 (14.58)	132.65 (14.88)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c (Glycosylated Haemoglobin) From Baseline
Description	Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	409	409	407
Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin]	-1.32 (0.05)	-1.61 (0.05)	-0.55 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 1.0 mg + Sitagliptin Placebo, Sitagliptin + Semaglutide Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was concluded if the upper limit of the two-sided 95% confidence interval for the estimated treatment difference between semaglutide 1.0 mg and sitagliptin was below the pre-specified non-inferiority margin (0.3 %).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Post-baseline responses analysed with mixed model for repeated measurements-treatment & country (fixed) & baseline (covariate) all nested within visit
Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 0.5 mg + Sitagliptin Placebo, Sitagliptin + Semaglutide Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was concluded if the upper limit of the two-sided 95% confidence interval for the estimated treatment difference between semaglutide 0.5 mg and sitagliptin was below the pre-specified non-inferiority margin (0.3 %).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Analysis done with mixed model for repeated measurements (treatment & country as fixed factors & baseline value as covariate) all nested within visit
Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight From Baseline
Description	Change in body weight from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	409	409	407
Least Squares Mean (Standard Error) [kilograms]	-4.28 (0.25)	-6.13 (0.25)	-1.93 (0.26)

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline
Description	Change in fasting plasma glucose from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	409	409	407
Least Squares Mean (Standard Error) [mg/dL]	-37.38 (1.79)	-46.72 (1.78)	-19.85 (1.88)

4. Secondary Outcome

Title	Change in Systolic and Diastolic Blood Pressure From Baseline
Description	Change in systolic and diastolic blood pressure from baseline to week 56. Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	409	409	407
Systolic blood pressure	-5.07 (0.64)	-5.61 (0.63)	-2.29 (0.67)
Diastolic blood pressure	-2.01 (0.42)	-1.91 (0.42)	-1.11 (0.44)

5. Secondary Outcome

Title	Change in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) From Baseline
Description	Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin. The DTSQs questionnaire was used to assess subjects' treatment satisfaction. This questionnaire contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Out of the 1225 subjects in FAS, 76 in semaglutide 0.5 mg arm, 76 in semaglutide 1.0 mg arm, and 113 in placebo arm had missing data for the endpoint. Missing data imputed from a mixed model for repeated measurements for treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	333	333	294
Least Squares Mean (Standard Error) [Units on a scale]	5.28 (0.23)	5.91 (0.23)	4.45 (0.24)

6. Secondary Outcome

Title	Subjects Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Description	Subjects who achieved HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target (yes/no) after week 56 weeks of treatment.
Time Frame	After 56 weeks treatment

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of semaglutide or sitagliptin

Arm/Group Title	Semaglutide 0.5 mg + Sitagliptin Placebo	Semaglutide 1.0 mg + Sitagliptin Placebo	Sitagliptin + Semaglutide Placebo
Arm/Group Description	Semaglutide 0.5 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Semaglutide 1.0 mg administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin placebo (0 mg) administered orally once daily.	Subjects were randomised to 2 different placebo arms (sitagliptin + semaglutide placebo 0.5 mg and sitagliptin + semaglutide placebo 1.0 mg). Both arms were pooled together for data analysis. Semaglutide placebo administered subcutaneously (s.c., under the skin) once weekly, in the thigh, abdomen, or upper arm, at any time of day irrespective of meals. Sitagliptin (100 mg) administered orally once daily.
Measure Participants	409	409	407
Yes	215	270	83
No	194	139	324

Adverse Events

Time Frame	Adverse events are reported for on-treatment period i.e from the date of initiation of trial product to the end of the on-treatment period (up to 56 weeks).
Adverse Event Reporting Description	Safety analysis set included all subjects exposed to at least one dose of semaglutide or sitagliptin. Number of deaths causally related to treatment is the data considered to present under 'total number of deaths resulting from adverse events'.
Arm/Group Title	Semaglutide 1.0 mg + Sitagliptin Placebo		Semaglutide 0.5 mg + Sitagliptin Placebo		Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg		Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg
Arm/Group Description	Semaglutide 1.0 mg once-weekly + Sitagliptin placebo once-daily		Semaglutide 0.5 mg once-weekly + Sitagliptin placebo once-daily		Sitagliptin 100 mg once-daily + Semaglutide placebo 1.0 mg once-weekly		Sitagliptin 100 mg once-daily + Semaglutide placebo 0.5 mg once-weekly
All Cause Mortality
	Semaglutide 1.0 mg + Sitagliptin Placebo		Semaglutide 0.5 mg + Sitagliptin Placebo		Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg		Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Semaglutide 1.0 mg + Sitagliptin Placebo		Semaglutide 0.5 mg + Sitagliptin Placebo		Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg		Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/409 (7.3%)		30/409 (7.3%)		13/204 (6.4%)		16/203 (7.9%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Anaemia	1/409 (0.2%)	1	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Lymphadenitis	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Splenic lesion	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Cardiac disorders
Angina pectoris	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Atrial fibrillation	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Atrioventricular block second degree	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Cardiac arrest	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Cardiac failure	1/409 (0.2%)	1	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Cardio-respiratory arrest	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Cardiovascular disorder	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Congestive cardiomyopathy	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Coronary artery disease	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Ischaemic cardiomyopathy	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Myocardial infarction	1/409 (0.2%)	1	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Myocardial ischaemia	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Endocrine disorders
Goitre	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Eye disorders
Cataract	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Gastrointestinal disorders
Abdominal pain lower	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Abdominal pain upper	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Chronic gastritis	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Colitis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Diarrhoea	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Enteritis	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Gastritis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Gastritis erosive	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Haemorrhoids	0/409 (0%)	0	2/409 (0.5%)	2	0/204 (0%)	0	0/203 (0%)	0
Inguinal hernia	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Intestinal obstruction	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Large intestine polyp	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Mallory-Weiss syndrome	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Pancreatic disorder	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Pancreatitis	0/409 (0%)	0	2/409 (0.5%)	2	0/204 (0%)	0	0/203 (0%)	0
Pancreatitis acute	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Pancreatitis necrotising	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Papilla of Vater stenosis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Swollen tongue	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Umbilical hernia	1/409 (0.2%)	1	2/409 (0.5%)	2	0/204 (0%)	0	1/203 (0.5%)	1
General disorders
Death	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Fatigue	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Granuloma	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Non-cardiac chest pain	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Pyrexia	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Cholecystitis acute	2/409 (0.5%)	2	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Cholelithiasis	2/409 (0.5%)	2	1/409 (0.2%)	1	0/204 (0%)	0	1/203 (0.5%)	1
Drug-induced liver injury	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Infections and infestations
Appendicitis	1/409 (0.2%)	1	1/409 (0.2%)	1	1/204 (0.5%)	1	0/203 (0%)	0
Appendicitis perforated	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Arthritis bacterial	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Epiglottitis	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Gastroenteritis viral	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Lower respiratory tract infection	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Perineal abscess	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Peritonitis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	1/203 (0.5%)	1
Pneumonia	0/409 (0%)	0	2/409 (0.5%)	2	0/204 (0%)	0	0/203 (0%)	0
Pyelonephritis acute	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Pyelonephritis chronic	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Sinusitis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Urosepsis	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Injury, poisoning and procedural complications
Gas poisoning	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Hand fracture	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Post procedural haemorrhage	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Road traffic accident	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Investigations
Haemoglobin decreased	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Troponin I increased	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Hyperglycaemia	0/409 (0%)	0	1/409 (0.2%)	1	1/204 (0.5%)	1	1/203 (0.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Intervertebral disc protrusion	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Ligamentitis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Lumbar spinal stenosis	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Musculoskeletal chest pain	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Osteitis	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of eyelid	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Bladder cancer	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Metastatic neoplasm	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Neuroendocrine carcinoma metastatic	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Papillary thyroid cancer	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Thyroid adenoma	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Uterine leiomyoma	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Nervous system disorders
Cerebrovascular accident	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Hypoglycaemic unconsciousness	0/409 (0%)	0	0/409 (0%)	0	1/204 (0.5%)	1	0/203 (0%)	0
Ischaemic stroke	0/409 (0%)	0	0/409 (0%)	0	2/204 (1%)	2	1/203 (0.5%)	1
Syncope	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Psychiatric disorders
Depression	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Renal and urinary disorders
Calculus bladder	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Glycosuria	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Hydronephrosis	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Ketonuria	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Nephrolithiasis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Renal failure	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Ovarian cyst	0/409 (0%)	0	0/409 (0%)	0	0/204 (0%)	0	1/203 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Chronic obstructive pulmonary disease	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Dyspnoea	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Epistaxis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Pharyngeal oedema	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Dermatitis	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Xanthelasma	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Surgical and medical procedures
Haemorrhoid operation	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Meniscus operation	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Vascular disorders
Deep vein thrombosis	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Hypertensive emergency	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Hypovolaemic shock	0/409 (0%)	0	1/409 (0.2%)	1	0/204 (0%)	0	0/203 (0%)	0
Peripheral venous disease	1/409 (0.2%)	1	0/409 (0%)	0	0/204 (0%)	0	0/203 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 1.0 mg + Sitagliptin Placebo		Semaglutide 0.5 mg + Sitagliptin Placebo		Sitagliptin 100 mg + Semaglutide Placebo 1.0 mg		Sitagliptin 100 mg + Semaglutide Placebo 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	197/409 (48.2%)		208/409 (50.9%)		75/204 (36.8%)		85/203 (41.9%)
Gastrointestinal disorders
Constipation	23/409 (5.6%)	29	18/409 (4.4%)	20	5/204 (2.5%)	5	3/203 (1.5%)	4
Diarrhoea	53/409 (13%)	85	53/409 (13%)	91	13/204 (6.4%)	17	16/203 (7.9%)	18
Dyspepsia	20/409 (4.9%)	27	26/409 (6.4%)	28	4/204 (2%)	4	5/203 (2.5%)	7
Nausea	72/409 (17.6%)	140	73/409 (17.8%)	110	13/204 (6.4%)	15	17/203 (8.4%)	23
Vomiting	41/409 (10%)	119	33/409 (8.1%)	49	6/204 (2.9%)	7	5/203 (2.5%)	9
Infections and infestations
Influenza	22/409 (5.4%)	25	18/409 (4.4%)	23	13/204 (6.4%)	14	14/203 (6.9%)	16
Nasopharyngitis	29/409 (7.1%)	33	50/409 (12.2%)	63	19/204 (9.3%)	20	23/203 (11.3%)	31
Pharyngitis	10/409 (2.4%)	12	7/409 (1.7%)	7	5/204 (2.5%)	5	13/203 (6.4%)	16
Investigations
Lipase increased	32/409 (7.8%)	38	33/409 (8.1%)	41	13/204 (6.4%)	16	16/203 (7.9%)	17
Metabolism and nutrition disorders
Decreased appetite	27/409 (6.6%)	29	26/409 (6.4%)	28	6/204 (2.9%)	6	5/203 (2.5%)	5
Nervous system disorders
Headache	29/409 (7.1%)	42	26/409 (6.4%)	81	9/204 (4.4%)	19	8/203 (3.9%)	10

Limitations/Caveats

None reported

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 investigators(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.