SUSTAIN™ 6: Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT01720446
Collaborator
(none)
3,297
253
4
36.7
13
0.4

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes. The trial is event-driven, i.e. the maximum trial duration (up to max. 148 weeks) will depend on the accrual of major adverse cardiovascular events (MACE) in this trial and the remaining research programme. The incidence of MACE will be monitored throughout the trial which will be terminated according to plan when pre-specified stopping criteria are met.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
3297 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6 - Long-term Outcomes)
Actual Study Start Date :
Feb 21, 2013
Actual Primary Completion Date :
Mar 15, 2016
Actual Study Completion Date :
Mar 15, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Semaglutide 0.5 mg

Drug: semaglutide
Once weekly doses of 0.5 mg semaglutide after an initial dose escalation step of 0.25 mg as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)

Experimental: Semaglutide 1.0 mg

Drug: semaglutide
Once weekly doses of 1.0 mg semaglutide after an initial dose escalation step of 0.25 mg followed by 0.5 mg dose escalation as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)

Placebo Comparator: Semaglutide placebo 0.5 mg

Drug: placebo
Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin).

Placebo Comparator: Semaglutide placebo 1.0 mg

Drug: placebo
Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin).

Outcome Measures

Primary Outcome Measures

  1. Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke [Time from randomisation up to end of follow-up (scheduled at week 109)]

    Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke.

Secondary Outcome Measures

  1. Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome [Time from randomisation up to end of follow-up (scheduled at week 109)]

    Percentage of subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure)

  2. Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome [Time from randomisation up to end of follow-up (scheduled at week 109)]

    Percentage of subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure).

  3. Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke [Time from randomisation up to end of follow-up (scheduled at week 109)]

    Percentage of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke.

  4. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c) [Week 0, up to week 104]

    Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period.

  5. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose [Week 0, up to week 104]

    Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period.

  6. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight [Week 0, up to week 104]

    Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period.

  7. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile [Week 0, up to week 104]

    Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides).

  8. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio [Week 0, up to week 104]

    Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period.

  9. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs [Week 0, up to week 104]

    Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure).

  10. Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events [Week 0 - 109]

    Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the American diabetic association (ADA) classification or blood glucose (BG) confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  11. Incidence During the Trial in Other Treatment Outcomes: Adverse Events [Weeks 0-109]

    Rates (event rate per 100 years of exposure) of treatment emergent adverse events.

  12. Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies [Weeks 0-109]

    The percentage of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109.

  13. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO) [Week 0, up to week 104]

    Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire (SF-36v2TM) measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0-100 scale with higher scores indicating greater health related quality of life.

  14. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids) [Week 0, up to week 104]

    Estimated ratio to baseline at week 104 during the treatment period in lipid profile (free fatty acids).

  15. Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate) [Week 0, up to week 104]

    Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate).

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Men and women with type 2 diabetes mellitus - Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease or age above or equal to 60 years at screening and subclinical evidence of cardiovascular disease - Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs - HbA1c above or equal to 7.0% at screening Exclusion Criteria: - Type 1 diabetes mellitus - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening - Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening - Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening - History of chronic pancreatitis or idiopathic acute pancreatitis - Acute coronary or cerebro-vascular event within 90 days prior to randomisation - Currently planned coronary, carotid or peripheral artery revascularisation - Chronic heart failure New York Heart Association (NYHA) class IV - Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma - Personal history of non-familial medullary thyroid carcinoma

  • Screening calcitonin above or equal to 50 ng/L

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novo Nordisk Investigational Site Birmingham Alabama United States 35205-4731
2 Novo Nordisk Investigational Site Birmingham Alabama United States 35216
3 Novo Nordisk Investigational Site Chandler Arizona United States 85224
4 Novo Nordisk Investigational Site Anaheim California United States 92801
5 Novo Nordisk Investigational Site Greenbrae California United States 94904
6 Novo Nordisk Investigational Site Lancaster California United States 93534
7 Novo Nordisk Investigational Site Los Angeles California United States 90017-4006
8 Novo Nordisk Investigational Site Mission Hills California United States 91345
9 Novo Nordisk Investigational Site Monterey California United States 93940
10 Novo Nordisk Investigational Site Northridge California United States 91325
11 Novo Nordisk Investigational Site San Diego California United States 92108
12 Novo Nordisk Investigational Site San Ramon California United States 94583
13 Novo Nordisk Investigational Site Ventura California United States 93003
14 Novo Nordisk Investigational Site Aurora Colorado United States 80045
15 Novo Nordisk Investigational Site Waterbury Connecticut United States 06708
16 Novo Nordisk Investigational Site Bradenton Florida United States 34201
17 Novo Nordisk Investigational Site Crystal River Florida United States 34429
18 Novo Nordisk Investigational Site DeLand Florida United States 32724
19 Novo Nordisk Investigational Site Jacksonville Florida United States 32216
20 Novo Nordisk Investigational Site Melbourne Florida United States 32901
21 Novo Nordisk Investigational Site Melbourne Florida United States 32934
22 Novo Nordisk Investigational Site Ocala Florida United States 34470
23 Novo Nordisk Investigational Site Ponte Vedra Florida United States 32081
24 Novo Nordisk Investigational Site Saint Petersburg Florida United States 33707
25 Novo Nordisk Investigational Site Spring Hill Florida United States 34609
26 Novo Nordisk Investigational Site Dunwoody Georgia United States 30338
27 Novo Nordisk Investigational Site Lawrenceville Georgia United States 30046
28 Novo Nordisk Investigational Site Chicago Illinois United States 60607
29 Novo Nordisk Investigational Site Crystal Lake Illinois United States 60012
30 Novo Nordisk Investigational Site Gurnee Illinois United States 60031
31 Novo Nordisk Investigational Site Michigan City Indiana United States 46360
32 Novo Nordisk Investigational Site Mishawaka Indiana United States 46544
33 Novo Nordisk Investigational Site Wichita Kansas United States 67205
34 Novo Nordisk Investigational Site Louisville Kentucky United States 40206
35 Novo Nordisk Investigational Site Louisville Kentucky United States 40213
36 Novo Nordisk Investigational Site Monroe Louisiana United States 71203
37 Novo Nordisk Investigational Site New Orleans Louisiana United States 70112
38 Novo Nordisk Investigational Site Methuen Massachusetts United States 01844
39 Novo Nordisk Investigational Site North Dartmouth Massachusetts United States 02747
40 Novo Nordisk Investigational Site Kalamazoo Michigan United States 49048
41 Novo Nordisk Investigational Site Chesterfield Missouri United States 63017
42 Novo Nordisk Investigational Site Kansas City Missouri United States 64111
43 Novo Nordisk Investigational Site Saint Louis Missouri United States 63128
44 Novo Nordisk Investigational Site Saint Louis Missouri United States 63141
45 Novo Nordisk Investigational Site Omaha Nebraska United States 68114
46 Novo Nordisk Investigational Site Omaha Nebraska United States 68198-3020
47 Novo Nordisk Investigational Site Lebanon New Hampshire United States 03756
48 Novo Nordisk Investigational Site Nashua New Hampshire United States 03063
49 Novo Nordisk Investigational Site Mine Hill New Jersey United States 07803
50 Novo Nordisk Investigational Site Toms River New Jersey United States 08755-8050
51 Novo Nordisk Investigational Site Albany New York United States 12206
52 Novo Nordisk Investigational Site New York New York United States 10001
53 Novo Nordisk Investigational Site Rochester New York United States 14609
54 Novo Nordisk Investigational Site Staten Island New York United States 10301
55 Novo Nordisk Investigational Site West Seneca New York United States 14224
56 Novo Nordisk Investigational Site Asheboro North Carolina United States 27203
57 Novo Nordisk Investigational Site Asheville North Carolina United States 28801
58 Novo Nordisk Investigational Site Chapel Hill North Carolina United States 27517
59 Novo Nordisk Investigational Site Greenville North Carolina United States 27834
60 Novo Nordisk Investigational Site Raleigh North Carolina United States 27612
61 Novo Nordisk Investigational Site Whiteville North Carolina United States 28472
62 Novo Nordisk Investigational Site Wilmington North Carolina United States 28401
63 Novo Nordisk Investigational Site Cincinnati Ohio United States 45219
64 Novo Nordisk Investigational Site Cleveland Ohio United States 44106
65 Novo Nordisk Investigational Site Franklin Ohio United States 45005
66 Novo Nordisk Investigational Site Mason Ohio United States 45040-6815
67 Novo Nordisk Investigational Site Maumee Ohio United States 43537
68 Novo Nordisk Investigational Site Oklahoma City Oklahoma United States 73104
69 Novo Nordisk Investigational Site Beaver Pennsylvania United States 15009-1957
70 Novo Nordisk Investigational Site McMurray Pennsylvania United States 15317
71 Novo Nordisk Investigational Site Philadelphia Pennsylvania United States 19114
72 Novo Nordisk Investigational Site Greer South Carolina United States 29651
73 Novo Nordisk Investigational Site Myrtle Beach South Carolina United States 29572
74 Novo Nordisk Investigational Site Bartlett Tennessee United States 38133
75 Novo Nordisk Investigational Site Kingsport Tennessee United States 37660
76 Novo Nordisk Investigational Site Memphis Tennessee United States 38163
77 Novo Nordisk Investigational Site Nashville Tennessee United States 37212
78 Novo Nordisk Investigational Site Dallas Texas United States 75218
79 Novo Nordisk Investigational Site Dallas Texas United States 75230
80 Novo Nordisk Investigational Site Dallas Texas United States 75231
81 Novo Nordisk Investigational Site Dallas Texas United States 75390-9302
82 Novo Nordisk Investigational Site Fort Worth Texas United States 76132
83 Novo Nordisk Investigational Site Houston Texas United States 77074
84 Novo Nordisk Investigational Site Irving Texas United States 75061-2210
85 Novo Nordisk Investigational Site Longview Texas United States 75605
86 Novo Nordisk Investigational Site Odessa Texas United States 79761
87 Novo Nordisk Investigational Site Plano Texas United States 75075
88 Novo Nordisk Investigational Site San Antonio Texas United States 78224
89 Novo Nordisk Investigational Site San Antonio Texas United States 78228-3419
90 Novo Nordisk Investigational Site Sugar Land Texas United States 77478
91 Novo Nordisk Investigational Site Salt Lake City Utah United States 84107
92 Novo Nordisk Investigational Site South Burlington Vermont United States 05403-7205
93 Novo Nordisk Investigational Site Richmond Virginia United States 23219
94 Novo Nordisk Investigational Site Winchester Virginia United States 22601-3834
95 Novo Nordisk Investigational Site Winchester Virginia United States 22601
96 Novo Nordisk Investigational Site Wenatchee Washington United States 98801-2028
97 Novo Nordisk Investigational Site Madison Wisconsin United States 53792
98 Novo Nordisk Investigational Site Annaba Algeria 23000
99 Novo Nordisk Investigational Site Oran Algeria 31000
100 Novo Nordisk Investigational Site Setif Algeria 19000
101 Novo Nordisk Investigational Site Tizi Ouzou Algeria 15000
102 Novo Nordisk Investigational Site Caba Argentina C1093AAS
103 Novo Nordisk Investigational Site Caba Argentina C1180AAX
104 Novo Nordisk Investigational Site Caba Argentina C1440AAD
105 Novo Nordisk Investigational Site Caba Argentina
106 Novo Nordisk Investigational Site Cordoba Argentina 5000
107 Novo Nordisk Investigational Site Mar del Plata Argentina B7600FZN
108 Novo Nordisk Investigational Site Morón Argentina B1708IFF
109 Novo Nordisk Investigational Site Blacktown New South Wales Australia 2148
110 Novo Nordisk Investigational Site St Leonards New South Wales Australia 2065
111 Novo Nordisk Investigational Site Ipswich Queensland Australia 4305
112 Novo Nordisk Investigational Site Keswick South Australia Australia 5035
113 Novo Nordisk Investigational Site Oaklands Park South Australia Australia 5046
114 Novo Nordisk Investigational Site Box Hill Victoria Australia 3128
115 Novo Nordisk Investigational Site Fitzroy Victoria Australia 3065
116 Novo Nordisk Investigational Site Fremantle Western Australia Australia 6160
117 Novo Nordisk Investigational Site Curitiba Parana Brazil 80030-110
118 Novo Nordisk Investigational Site Belém Para Brazil 66073-000
119 Novo Nordisk Investigational Site Campinas Sao Paulo Brazil 13059-740
120 Novo Nordisk Investigational Site São Paulo Sao Paulo Brazil 01228-000
121 Novo Nordisk Investigational Site São Paulo Sao Paulo Brazil 01228-200
122 Novo Nordisk Investigational Site São Paulo Sao Paulo Brazil 04038-002
123 Novo Nordisk Investigational Site São Paulo Sao Paulo Brazil 05403-000
124 Novo Nordisk Investigational Site Porto Alegre Brazil 90035-170
125 Novo Nordisk Investigational Site Pleven Bulgaria 5800
126 Novo Nordisk Investigational Site Sofia Bulgaria 1324
127 Novo Nordisk Investigational Site Sofia Bulgaria 1606
128 Novo Nordisk Investigational Site Varna Bulgaria 9010
129 Novo Nordisk Investigational Site Calgary Alberta Canada T2V 4J2
130 Novo Nordisk Investigational Site Edmonton Alberta Canada T6G 2E1
131 Novo Nordisk Investigational Site Winnipeg Manitoba Canada R3E 3P4
132 Novo Nordisk Investigational Site St. John's Newfoundland and Labrador Canada A1E 2C2
133 Novo Nordisk Investigational Site Cambridge Ontario Canada N1R 7L6
134 Novo Nordisk Investigational Site Cornwall Ontario Canada K6H 4M4
135 Novo Nordisk Investigational Site London Ontario Canada N6A 4V2
136 Novo Nordisk Investigational Site Smiths Falls Ontario Canada K7A 4W8
137 Novo Nordisk Investigational Site Toronto Ontario Canada M5C 2T2
138 Novo Nordisk Investigational Site Waterloo Ontario Canada N2J 1C4
139 Novo Nordisk Investigational Site Drummondville Quebec Canada J2B 7T1
140 Novo Nordisk Investigational Site Montreal Quebec Canada H4A 3T2
141 Novo Nordisk Investigational Site Victoriaville Quebec Canada G6P 6P6
142 Novo Nordisk Investigational Site Quebec Canada G1V 4G5
143 Novo Nordisk Investigational Site Aarhus C Denmark 8000
144 Novo Nordisk Investigational Site Gentofte Denmark 2820
145 Novo Nordisk Investigational Site Hellerup Denmark 2900
146 Novo Nordisk Investigational Site Hvidovre Denmark 2650
147 Novo Nordisk Investigational Site Odense Denmark 5000
148 Novo Nordisk Investigational Site Elsterwerda Germany 04910
149 Novo Nordisk Investigational Site Essen Germany 45219
150 Novo Nordisk Investigational Site Falkensee Germany 14612
151 Novo Nordisk Investigational Site Freiburg Germany 79106
152 Novo Nordisk Investigational Site Hamburg Germany 22607
153 Novo Nordisk Investigational Site Münster Germany 48145
154 Novo Nordisk Investigational Site Oldenburg Germany 23758
155 Novo Nordisk Investigational Site Saint Ingbert Germany 66386
156 Novo Nordisk Investigational Site Hyderabad Andhra Pradesh India 500003
157 Novo Nordisk Investigational Site Hyderabad Andhra Pradesh India 500034
158 Novo Nordisk Investigational Site Hyderabad Andhra Pradesh India 500082
159 Novo Nordisk Investigational Site Visakhapatnam Andhra Pradesh India 530002
160 Novo Nordisk Investigational Site Bangalore Karnataka India 560034
161 Novo Nordisk Investigational Site Mysore Karnataka India 570001
162 Novo Nordisk Investigational Site Kochi Kerala India 682041
163 Novo Nordisk Investigational Site Mumbai Maharashtra India 400008
164 Novo Nordisk Investigational Site Mumbai Maharashtra India 400010
165 Novo Nordisk Investigational Site Mumbai Maharashtra India 400012
166 Novo Nordisk Investigational Site Mumbai Maharashtra India 400016
167 Novo Nordisk Investigational Site Mumbai Maharashtra India 400022
168 Novo Nordisk Investigational Site Delhi New Delhi India 110002
169 Novo Nordisk Investigational Site New Dehli New Delhi India 110029
170 Novo Nordisk Investigational Site Chandigarh Punjab India 160012
171 Novo Nordisk Investigational Site Chennai Tamil Nadu India 600086
172 Novo Nordisk Investigational Site Vellore Tamil Nadu India 632004
173 Novo Nordisk Investigational Site Kolkata West Bengal India 700032
174 Novo Nordisk Investigational Site Kolkata West Bengal India 700054
175 Novo Nordisk Investigational Site New Delhi India 110095
176 Novo Nordisk Investigational Site Pune India 411011
177 Novo Nordisk Investigational Site Holon Israel 58100
178 Novo Nordisk Investigational Site Jerusalem Israel 91120
179 Novo Nordisk Investigational Site Nahariya Israel 22100
180 Novo Nordisk Investigational Site Petah-Tikva Israel 49100
181 Novo Nordisk Investigational Site Tel Hashomer Israel 52621
182 Novo Nordisk Investigational Site Tel-Aviv Israel 64239
183 Novo Nordisk Investigational Site Bergamo Italy 24127
184 Novo Nordisk Investigational Site Chieti Italy 66100
185 Novo Nordisk Investigational Site Olbia Italy 07026
186 Novo Nordisk Investigational Site Padova Italy 35128
187 Novo Nordisk Investigational Site Primo Piano Palazzina Ambulato Italy 40133
188 Novo Nordisk Investigational Site Siena Italy 53100
189 Novo Nordisk Investigational Site Kota Samarahan Malaysia 94300
190 Novo Nordisk Investigational Site Kuala Lumpur Malaysia 59100
191 Novo Nordisk Investigational Site Kuching Malaysia 93586
192 Novo Nordisk Investigational Site Melaka Malaysia 75400
193 Novo Nordisk Investigational Site Serdang Malaysia 43000
194 Novo Nordisk Investigational Site Seremban Malaysia 70300
195 Novo Nordisk Investigational Site Guadalajara Jalisco Mexico 44130
196 Novo Nordisk Investigational Site Guadalajara Jalisco Mexico 44600
197 Novo Nordisk Investigational Site Guadalajara Jalisco Mexico 44670
198 Novo Nordisk Investigational Site Cuernavaca Morelos Mexico 62250
199 Novo Nordisk Investigational Site Mexico City México, D.F. Mexico 03300
200 Novo Nordisk Investigational Site Mexico City México, D.F. Mexico 14000
201 Novo Nordisk Investigational Site México D.F. México, D.F. Mexico 11550
202 Novo Nordisk Investigational Site Ciudad Madero Tamaulipas Mexico 89440
203 Novo Nordisk Investigational Site Aguascalientes Mexico 20230
204 Novo Nordisk Investigational Site San Luis Potosi Mexico 78200
205 Novo Nordisk Investigational Site Bialystok Poland 15-445
206 Novo Nordisk Investigational Site Gdansk Poland 80-858
207 Novo Nordisk Investigational Site Lublin Poland 20-044
208 Novo Nordisk Investigational Site Warszawa Poland 01-192
209 Novo Nordisk Investigational Site Zabrze Poland 41-800
210 Novo Nordisk Investigational Site Arkhangelsk Russian Federation 163001
211 Novo Nordisk Investigational Site Arkhangelsk Russian Federation 163045
212 Novo Nordisk Investigational Site Barnaul Russian Federation 656045
213 Novo Nordisk Investigational Site Kazan Russian Federation 420043
214 Novo Nordisk Investigational Site Moscow Russian Federation 117997
215 Novo Nordisk Investigational Site Moscow Russian Federation 119435
216 Novo Nordisk Investigational Site Novosibirsk Russian Federation 630047
217 Novo Nordisk Investigational Site Penza Russian Federation 440026
218 Novo Nordisk Investigational Site Saint-Petersburg Russian Federation 199034
219 Novo Nordisk Investigational Site Saratov Russian Federation 410031
220 Novo Nordisk Investigational Site Saratov Russian Federation 410053
221 Novo Nordisk Investigational Site Smolensk Russian Federation 214019
222 Novo Nordisk Investigational Site Yaroslavl Russian Federation 150062
223 Novo Nordisk Investigational Site Almería Spain 04001
224 Novo Nordisk Investigational Site Antequera Spain 29200
225 Novo Nordisk Investigational Site Pozuelo de Alarcon Spain 28223
226 Novo Nordisk Investigational Site Sanlúcar De Barrameda - Cádiz- Spain 15540
227 Novo Nordisk Investigational Site Sevilla Spain 41010
228 Novo Nordisk Investigational Site Vic (Barcelona) Spain 08500
229 Novo Nordisk Investigational Site Chiayi City Taiwan 600
230 Novo Nordisk Investigational Site Tainan city Taiwan 710
231 Novo Nordisk Investigational Site Taipei Taiwan 114
232 Novo Nordisk Investigational Site Taoyuan Taiwan 333
233 Novo Nordisk Investigational Site Bangkok Thailand 10330
234 Novo Nordisk Investigational Site Bangkok Thailand 10400
235 Novo Nordisk Investigational Site Bangkok Thailand 10700
236 Novo Nordisk Investigational Site Ankara Turkey 06100
237 Novo Nordisk Investigational Site Ankara Turkey 06110
238 Novo Nordisk Investigational Site Antalya Turkey 07058
239 Novo Nordisk Investigational Site Canakkale Turkey 17020
240 Novo Nordisk Investigational Site Denizli Turkey 20070
241 Novo Nordisk Investigational Site Istanbul Turkey 34096
242 Novo Nordisk Investigational Site Istanbul Turkey 34722
243 Novo Nordisk Investigational Site Istanbul Turkey 34890
244 Novo Nordisk Investigational Site Izmir Turkey 35340
245 Novo Nordisk Investigational Site Kocaeli Turkey 41380
246 Novo Nordisk Investigational Site Aberdeen United Kingdom AB25 2ZD
247 Novo Nordisk Investigational Site Birmingham United Kingdom B9 5SS
248 Novo Nordisk Investigational Site Leeds United Kingdom LS25 1AN
249 Novo Nordisk Investigational Site Liverpool United Kingdom L9 7AL
250 Novo Nordisk Investigational Site Northwood United Kingdom HA6 2RN
251 Novo Nordisk Investigational Site Sidcup United Kingdom DA14 6LT
252 Novo Nordisk Investigational Site Swansea United Kingdom SA6 6NL
253 Novo Nordisk Investigational Site Torquay United Kingdom TQ2 7AA

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:

Publications

Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01720446
Other Study ID Numbers:
  • NN9535-3744
  • 2012-002839-28
  • U1111-1131-7227
First Posted:
Nov 2, 2012
Last Update Posted:
Jun 27, 2019
Last Verified:
Jun 1, 2019
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details The trial was conducted at 229 sites in 20 countries. Country (sites): Algeria (4), Argentina (7), Australia (8), Brazil (8), Bulgaria (5), Canada (13), Denmark (5), Germany (7), Israel (6), Italy (6), Malaysia (6), Mexico (9), Poland (5), Russia (11), Spain (6), Taiwan (4), Thailand (5), Turkey (10), United Kingdom (8) and United States (96).
Pre-assignment Detail Subjects could be anti-glycaemic drug naïve, or treated with 1 or 2 oral anti diabetic drugs (OADs), or treated with human NPH insulin or long-acting insulin analogue or pre-mixed insulin, alone or in combination with 1 or 2 OAD(s).
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Period Title: Overall Study
STARTED 826 822 824 825
Premature Treatment Discontinuers 164 186 151 159
COMPLETED 812 811 804 805
NOT COMPLETED 14 11 20 20

Baseline Characteristics

Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg Total
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Total of all reporting groups
Overall Participants 826 822 824 825 3297
Age, Customized (participants) [Number]
50-64 years
440
53.3%
415
50.5%
419
50.8%
425
51.5%
1699
51.5%
65-74 years
312
37.8%
324
39.4%
324
39.3%
317
38.4%
1277
38.7%
75-84 years
71
8.6%
76
9.2%
75
9.1%
79
9.6%
301
9.1%
85 and over
3
0.4%
7
0.9%
6
0.7%
4
0.5%
20
0.6%
Sex: Female, Male (Count of Participants)
Female
331
40.1%
304
37%
342
41.5%
318
38.5%
1295
39.3%
Male
495
59.9%
518
63%
482
58.5%
507
61.5%
2002
60.7%
Glycosylated haemoglobin (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]
8.67
(1.39)
8.73
(1.51)
8.70
(1.49)
8.70
(1.45)
8.70
(1.46)
Fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]
185.4
(66.09)
182.9
(68.04)
185.8
(68.23)
184.6
(63.08)
184.7
(66.37)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]
91.80
(20.25)
92.86
(21.05)
91.83
(20.35)
91.90
(20.75)
92.09
(20.60)
LDL-cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]
89.62
(39.08)
89.72
(34.49)
89.01
(38.35)
91.14
(37.90)
89.87
(37.49)
HDL-cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]
45.92
(13.00)
44.97
(12.42)
45.82
(12.92)
44.61
(12.26)
45.33
(12.66)
Systolic BP (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]
136.1
(17.97)
135.8
(16.96)
135.8
(16.16)
134.8
(17.45)
135.6
(17.15)
Diastolic BP (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]
77.10
(9.78)
76.88
(10.21)
77.54
(9.85)
76.66
(10.21)
77.05
(10.02)
Pulse rate (beats/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/min]
72.69
(11.22)
71.53
(10.86)
72.01
(10.62)
71.95
(10.92)
72.05
(10.91)
Total cholesterol (mg/dL) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [mg/dL]
165.38
164.96
164.38
165.97
165.17
Triglycerides (mg/dL) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [mg/dL]
163.66
158.93
162.30
163.00
161.96
Free fatty acids (mmol/L) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [mmol/L]
0.83
0.80
0.83
0.81
0.82

Outcome Measures

1. Primary Outcome
Title Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke
Description Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke.
Time Frame Time from randomisation up to end of follow-up (scheduled at week 109)

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint.
Arm/Group Title Semaglutide Placebo
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 1648 1649
Number [percentage of subjects]
6.6
8.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments The primary endpoint was analysed using a stratified Cox proportional hazards model with treatment group (semaglutide, placebo) as fixed factor. Assuming the same population MACE risk for the semaglutide and placebo groups (i.e., the population hazards ratio [HR] equals 1), a total minimum of 122 events were needed in order to have at least 90% power to ascertain that the upper two-sided 95% confidence limit for the HR was less than 1.8.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of semaglutide versus placebo was considered to be confirmed if the upper limit of the two-sided 95% CI for the HR was below 1.8 or equivalent if the p-value for the one-sided test of: H0: HR ≥ 1.8 against Ha: HR <1.8 was less than 2.5% (or equivalent to 5% for a two-sided test).
Statistical Test of Hypothesis p-Value <0.0001
Comments The 'p-value' is for the two-sided Wald test of non-inferiority with limit 1.8.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.58 to 0.95
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments A post hoc analysis of superiority of semaglutide versus placebo was performed based on the pre-specified Cox proportional hazard analysis using the two-sided Wald test of no difference, with treatment (semaglutide, placebo) as fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0167
Comments The 'p-value' is for the two-sided Wald test of no difference.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.58 to 0.95
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
2. Secondary Outcome
Title Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome
Description Percentage of subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure)
Time Frame Time from randomisation up to end of follow-up (scheduled at week 109)

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint.
Arm/Group Title Semaglutide Placebo
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 1648 1649
Number [percentage of subjects]
12.1
16.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0016
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.62 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
3. Secondary Outcome
Title Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome
Description Percentage of subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure).
Time Frame Time from randomisation up to end of follow-up (scheduled at week 109)

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint.
Arm/Group Title Semaglutide Placebo
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 1648 1649
Cardiovascular death
1.6
1.9
Non-fatal MI
2.5
3.7
Non-fatal Stroke
1.5
2.5
Revascularisation
2.6
4.2
UAP requiring hospitalisation
1.1
1.3
Hospitalisation for heart failure
2.7
2.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for CV death was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9181
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.65 to 1.48
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for non-fatal myocardial infarction was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1194
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.51 to 1.08
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0438
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.38 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for revascularisation was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0027
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.50 to 0.86
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for 'unstable angina requiring hospitalisation' was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4914
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.47 to 1.44
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for hospitalisation for heart failure was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5735
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.77 to 1.61
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placcbo
4. Secondary Outcome
Title Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke
Description Percentage of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke.
Time Frame Time from randomisation up to end of follow-up (scheduled at week 109)

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint.
Arm/Group Title Semaglutide Placebo
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 1648 1649
Number [percentage of subjects]
7.4
9.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo
Comments Analysis for all-cause death, non-fatal MI or non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0292
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.61 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide/Placebo
5. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c)
Description Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period.
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin]
-1.09
(0.05)
-1.41
(0.05)
-0.44
(0.05)
-0.36
(0.05)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.66
Confidence Interval (2-Sided) 95%
-0.80 to -0.52
Parameter Dispersion Type:
Value:
Estimation Comments Sema 0.5 mg - Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-1.19 to -0.91
Parameter Dispersion Type:
Value:
Estimation Comments Sema 1.0 mg - Placebo 1.0 mg
6. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose
Description Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period.
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Least Squares Mean (Standard Error) [mmol/L]
-1.75
(0.12)
-2.11
(0.12)
-1.02
(0.12)
-0.88
(0.12)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-1.06 to -0.38
Parameter Dispersion Type:
Value:
Estimation Comments Sema 0.5 mg - Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-1.56 to -0.88
Parameter Dispersion Type:
Value:
Estimation Comments Sema 1.0 mg - Placebo 1.0 mg
7. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight
Description Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period.
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects. As specified in the protocol, the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 1649
Least Squares Mean (Standard Error) [kg]
-3.57
(0.21)
-4.88
(0.22)
-0.62
(0.15)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.95
Confidence Interval (2-Sided) 95%
-3.47 to -2.44
Parameter Dispersion Type:
Value:
Estimation Comments Sema 0.5 mg - Placebo
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 0.5 mg
Comments Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -4.27
Confidence Interval (2-Sided) 95%
-4.78 to -3.75
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo
8. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile
Description Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides).
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Total cholesterol (mg/dL)
0.97
(0.01)
0.97
(0.01)
1.00
(0.01)
0.99
(0.01)
HDL-cholesterol (mg/dL)
0.99
(0.01)
1.01
(0.01)
0.99
(0.01)
0.97
(0.01)
LDL-cholesterol (mg/dL)
0.97
(0.01)
0.98
(0.01)
1.01
(0.01)
0.99
(0.01)
Triglycerides (mg/dL)
0.93
(0.01)
0.92
(0.01)
0.96
(0.01)
0.98
(0.01)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0149
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.95 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg/Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2580
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.97 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg/Placebo 1.0 mg
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8106
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.99 to 1.02
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg/Placebo 0.5 mg
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
1.02 to 1.06
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg/Placebo 1.0 mg
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0185
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.93 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg/Placebo 0.5 mg
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5996
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.96 to 1.03
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg/Placebo 1.0 mg
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1833
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.93 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg/Placebo 0.5 mg
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0009
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.89 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg/Placebo 1.0 mg
9. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio
Description Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period.
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Least Squares Mean (Standard Error) [mg/g]
1.02
(0.05)
0.91
(0.05)
1.32
(0.07)
1.29
(0.06)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0003
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.68 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments Sema 0.5 mg / Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.62 to 0.81
Parameter Dispersion Type:
Value:
Estimation Comments Sema 1.0 mg / Placebo 1.0 mg
10. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs
Description Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure).
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Diastolic blood pressure (mmHg)
-1.37
(0.32)
-1.57
(0.32)
-1.42
(0.32)
-1.71
(0.32)
Systolic blood pressure (mmHg)
-3.44
(0.54)
-5.37
(0.54)
-2.17
(0.54)
-2.78
(0.54)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9205
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.83 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7477
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.74 to 1.03
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0976
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.27
Confidence Interval (2-Sided) 95%
-2.77 to 0.23
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0008
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.59
Confidence Interval (2-Sided) 95%
-4.09 to -1.08
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
11. Secondary Outcome
Title Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events
Description Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the American diabetic association (ADA) classification or blood glucose (BG) confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame Week 0 - 109

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Number [Event rate per 100 exposure years]
37.5
36.2
35.3
39.7
12. Secondary Outcome
Title Incidence During the Trial in Other Treatment Outcomes: Adverse Events
Description Rates (event rate per 100 years of exposure) of treatment emergent adverse events.
Time Frame Weeks 0-109

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Number [Event rate per 100 years of exposure]
330.5
337.0
317.4
298.3
13. Secondary Outcome
Title Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies
Description The percentage of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109.
Time Frame Weeks 0-109

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822
Number [Percentage of subjects]
1.4
2.3
14. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO)
Description Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire (SF-36v2TM) measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0-100 scale with higher scores indicating greater health related quality of life.
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Bodily pain
0.66
(0.35)
1.82
(0.35)
0.16
(0.35)
0.35
(0.35)
General health
1.66
(0.29)
2.55
(0.29)
0.78
(0.29)
1.13
(0.30)
Mental component summary
0.0
(0.35)
0.86
(0.35)
-0.17
(0.35)
-0.11
(0.35)
Mental health
0.48
(0.33)
1.08
(0.33)
-0.14
(0.33)
-0.31
(0.33)
Physical component summary
0.76
(0.28)
1.74
(0.28)
0.07
(0.28)
0.35
(0.28)
Physical functioning
0.42
(0.32)
1.12
(0.32)
-0.38
(0.32)
-0.37
(0.33)
Role-emotional
0.17
(0.42)
0.89
(0.42)
-0.36
(0.42)
-0.05
(0.42)
Role-physical
0.39
(0.34)
1.18
(0.35)
-0.33
(0.35)
0.03
(0.35)
Social functioning
-0.25
(0.35)
0.97
(0.35)
-0.20
(0.36)
-0.17
(0.36)
Vitality
0.29
(0.31)
1.55
(0.31)
-0.04
(0.31)
0.35
(0.31)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3171
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.48 to 1.47
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0031
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
0.50 to 2.45
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0350
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.06 to 1.69
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0007
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.60 to 2.24
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7277
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.79 to 1.13
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0489
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.00 to 1.94
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1860
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-0.30 to 1.53
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0029
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
0.48 to 2.31
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0833
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
-0.09 to 1.45
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0004
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
0.62 to 2.17
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0799
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-0.10 to 1.69
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0011
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.60 to 2.40
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3717
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-0.63 to 1.68
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1136
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
-0.22 to 2.10
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1431
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
-0.24 to 1.67
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0197
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.18 to 2.11
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9223
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-1.03 to 0.93
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0237
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.15 to 2.13
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4523
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-0.53 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0064
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.34 to 2.07
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg
15. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids)
Description Estimated ratio to baseline at week 104 during the treatment period in lipid profile (free fatty acids).
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Least Squares Mean (Standard Error) [mmol/L]
0.95
(0.02)
0.91
(0.01)
0.96
(0.02)
0.99
(0.02)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7796
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.95 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg/Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0003
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.88 to 0.96
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg/Placebo 1.0 mg
16. Secondary Outcome
Title Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate)
Description Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate).
Time Frame Week 0, up to week 104

Outcome Measure Data

Analysis Population Description
Full analysis set included all the randomised subjects.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Measure Participants 826 822 824 825
Least Squares Mean (Standard Error) [beats/min]
2.12
(0.34)
2.41
(0.34)
0.09
(0.34)
-0.07
(0.34)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide, Placebo 0.5 mg
Comments Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.02
Confidence Interval (2-Sided) 95%
1.07 to 2.98
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 0.5 mg - Placebo 0.5 mg
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Placebo 1.0 mg
Comments Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.47
Confidence Interval (2-Sided) 95%
1.52 to 3.43
Parameter Dispersion Type:
Value:
Estimation Comments Semaglutide 1.0 mg - Placebo 1.0 mg

Adverse Events

Time Frame Adverse events from the first trial-related activity after the subject had signed the informed consent (week -2) until the end of the posttreatment follow-up period (week 109).
Adverse Event Reporting Description Safety was assessed using the full analysis set which included all randomised subjects. Subjects contributed to the evaluation as randomised.
Arm/Group Title Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Arm/Group Description Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
All Cause Mortality
Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 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 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 289/826 (35%) 276/822 (33.6%) 329/824 (39.9%) 298/825 (36.1%)
Blood and lymphatic system disorders
Anaemia 5/826 (0.6%) 5 4/822 (0.5%) 4 2/824 (0.2%) 2 2/825 (0.2%) 2
Haemorrhagic anaemia 1/826 (0.1%) 1 2/822 (0.2%) 2 0/824 (0%) 0 1/825 (0.1%) 1
Iron deficiency anaemia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Leukocytosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Lymphadenopathy 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Lymphadenopathy mediastinal 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 0/825 (0%) 0
Microcytic anaemia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Splenic vein thrombosis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Splenomegaly 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Thrombocytopenia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cardiac disorders
Acute coronary syndrome 4/826 (0.5%) 4 3/822 (0.4%) 3 1/824 (0.1%) 1 2/825 (0.2%) 2
Acute left ventricular failure 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Acute myocardial infarction 16/826 (1.9%) 21 13/822 (1.6%) 14 15/824 (1.8%) 15 27/825 (3.3%) 28
Angina pectoris 9/826 (1.1%) 9 9/822 (1.1%) 10 16/824 (1.9%) 17 12/825 (1.5%) 12
Angina unstable 13/826 (1.6%) 16 15/822 (1.8%) 18 19/824 (2.3%) 21 22/825 (2.7%) 23
Aortic valve disease 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Aortic valve stenosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Arrhythmia 1/826 (0.1%) 2 1/822 (0.1%) 1 1/824 (0.1%) 1 3/825 (0.4%) 3
Arteriosclerosis coronary artery 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 3/825 (0.4%) 3
Atrial fibrillation 14/826 (1.7%) 16 12/822 (1.5%) 15 20/824 (2.4%) 22 18/825 (2.2%) 19
Atrial flutter 1/826 (0.1%) 1 1/822 (0.1%) 1 4/824 (0.5%) 4 1/825 (0.1%) 1
Atrioventricular block 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Atrioventricular block complete 1/826 (0.1%) 1 0/822 (0%) 0 2/824 (0.2%) 2 3/825 (0.4%) 3
Atrioventricular block first degree 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Atrioventricular block second degree 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 1/825 (0.1%) 1
Bradycardia 1/826 (0.1%) 1 1/822 (0.1%) 1 2/824 (0.2%) 2 2/825 (0.2%) 2
Bundle branch block left 2/826 (0.2%) 2 1/822 (0.1%) 1 0/824 (0%) 0 3/825 (0.4%) 3
Bundle branch block right 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Cardiac arrest 5/826 (0.6%) 6 2/822 (0.2%) 2 3/824 (0.4%) 3 2/825 (0.2%) 3
Cardiac asthma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cardiac failure 10/826 (1.2%) 11 10/822 (1.2%) 10 7/824 (0.8%) 9 3/825 (0.4%) 4
Cardiac failure acute 2/826 (0.2%) 2 0/822 (0%) 0 4/824 (0.5%) 4 1/825 (0.1%) 2
Cardiac failure chronic 8/826 (1%) 8 4/822 (0.5%) 4 6/824 (0.7%) 6 3/825 (0.4%) 3
Cardiac failure congestive 21/826 (2.5%) 31 14/822 (1.7%) 17 15/824 (1.8%) 19 18/825 (2.2%) 21
Cardiac tamponade 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cardiac ventricular thrombosis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cardio-respiratory arrest 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Cardiogenic shock 0/826 (0%) 0 1/822 (0.1%) 1 3/824 (0.4%) 3 1/825 (0.1%) 1
Cardiomyopathy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Cardiopulmonary failure 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Cardiovascular insufficiency 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Congestive cardiomyopathy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Coronary artery disease 11/826 (1.3%) 11 9/822 (1.1%) 9 5/824 (0.6%) 6 2/825 (0.2%) 3
Coronary artery insufficiency 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Coronary artery occlusion 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Coronary artery stenosis 7/826 (0.8%) 7 2/822 (0.2%) 2 4/824 (0.5%) 4 1/825 (0.1%) 1
Diabetic cardiomyopathy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hypertensive cardiomyopathy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Ischaemic cardiomyopathy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Left ventricular failure 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Mitral valve incompetence 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Myocardial infarction 4/826 (0.5%) 4 10/822 (1.2%) 10 9/824 (1.1%) 10 12/825 (1.5%) 14
Myocardial ischaemia 6/826 (0.7%) 6 2/822 (0.2%) 2 3/824 (0.4%) 3 2/825 (0.2%) 2
Myocarditis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Nodal arrhythmia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pericardial effusion 2/826 (0.2%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Right ventricular failure 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Silent myocardial infarction 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 0/825 (0%) 0
Sinus bradycardia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Sinus node dysfunction 0/826 (0%) 0 2/822 (0.2%) 2 2/824 (0.2%) 2 0/825 (0%) 0
Supraventricular extrasystoles 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Supraventricular tachycardia 2/826 (0.2%) 2 2/822 (0.2%) 2 2/824 (0.2%) 2 1/825 (0.1%) 1
Tachycardia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Tricuspid valve incompetence 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ventricular arrhythmia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ventricular asystole 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Ventricular extrasystoles 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Ventricular fibrillation 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 2/825 (0.2%) 2
Ventricular hypokinesia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Ventricular tachyarrhythmia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ventricular tachycardia 1/826 (0.1%) 1 8/822 (1%) 8 1/824 (0.1%) 2 2/825 (0.2%) 2
Atrial thrombosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Bradyarrhythmia 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 0/825 (0%) 0
Cor pulmonale acute 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pulmonary valve stenosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Stress cardiomyopathy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Congenital, familial and genetic disorders
Phimosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Ear and labyrinth disorders
Deafness neurosensory 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Otosclerosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Tympanic membrane perforation 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Vertigo 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Endocrine disorders
Goitre 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Hyperthyroidism 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Inappropriate antidiuretic hormone secretion 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Thyroid mass 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Eye disorders
Blindness 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cataract 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 5/825 (0.6%) 6
Cataract cortical 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cataract nuclear 1/826 (0.1%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cystoid macular oedema 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Diabetic retinopathy 4/826 (0.5%) 4 2/822 (0.2%) 3 2/824 (0.2%) 2 4/825 (0.5%) 4
Diplopia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Eyelid dermatochalasis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Eyelid ptosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Glaucoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Iridocyclitis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Macular fibrosis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Macular oedema 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Open angle glaucoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Optic ischaemic neuropathy 0/826 (0%) 0 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Retinal artery occlusion 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Retinal degeneration 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Retinal detachment 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 2/825 (0.2%) 2
Retinopathy haemorrhagic 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Vitreous haemorrhage 2/826 (0.2%) 2 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Amaurosis fugax 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gastrointestinal disorders
Abdominal mass 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Abdominal pain 2/826 (0.2%) 2 6/822 (0.7%) 6 2/824 (0.2%) 3 2/825 (0.2%) 2
Abdominal pain lower 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Abdominal pain upper 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Ascites 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Change of bowel habit 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Chronic gastritis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Colitis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Colitis ischaemic 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Colitis ulcerative 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Constipation 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Diarrhoea 2/826 (0.2%) 2 6/822 (0.7%) 6 2/824 (0.2%) 2 1/825 (0.1%) 1
Diverticulum 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Diverticulum intestinal 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Duodenal ulcer 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Duodenal ulcer haemorrhage 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Duodenitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Enterocolitis haemorrhagic 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Epigastric discomfort 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Faeces discoloured 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastric disorder 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gastric ileus 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastric polyps 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastric ulcer 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastric ulcer haemorrhage 2/826 (0.2%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Gastritis 1/826 (0.1%) 1 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
Gastritis haemorrhagic 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gastroduodenitis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastrointestinal haemorrhage 5/826 (0.6%) 5 1/822 (0.1%) 1 1/824 (0.1%) 1 4/825 (0.5%) 4
Gastrointestinal ischaemia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Gastrooesophageal reflux disease 3/826 (0.4%) 3 3/822 (0.4%) 3 0/824 (0%) 0 1/825 (0.1%) 1
Hiatus hernia 0/826 (0%) 0 1/822 (0.1%) 1 2/824 (0.2%) 2 0/825 (0%) 0
Impaired gastric emptying 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Inguinal hernia 4/826 (0.5%) 4 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Intestinal haemorrhage 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Intestinal ischaemia 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Intestinal obstruction 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Large intestinal haemorrhage 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Large intestine polyp 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 0/825 (0%) 0
Lower gastrointestinal haemorrhage 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Melaena 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Mouth ulceration 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Nausea 0/826 (0%) 0 3/822 (0.4%) 3 1/824 (0.1%) 1 1/825 (0.1%) 1
Pancreatic cyst 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pancreatitis 2/826 (0.2%) 2 0/822 (0%) 0 1/824 (0.1%) 1 4/825 (0.5%) 4
Pancreatitis acute 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Peptic ulcer 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Peritoneal haemorrhage 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Proctitis haemorrhagic 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Rectal prolapse 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Small intestinal obstruction 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 2/825 (0.2%) 2
Umbilical hernia 2/826 (0.2%) 2 0/822 (0%) 0 0/824 (0%) 0 2/825 (0.2%) 2
Upper gastrointestinal haemorrhage 2/826 (0.2%) 2 1/822 (0.1%) 1 2/824 (0.2%) 2 1/825 (0.1%) 1
Volvulus of small bowel 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Vomiting 0/826 (0%) 0 3/822 (0.4%) 3 2/824 (0.2%) 2 2/825 (0.2%) 2
Diaphragmatic hernia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Haematemesis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Intestinal perforation 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Oesophageal spasm 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pneumoperitoneum 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
General disorders
Asthenia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 2/825 (0.2%) 2
Chest discomfort 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Chest pain 1/826 (0.1%) 1 3/822 (0.4%) 3 5/824 (0.6%) 6 3/825 (0.4%) 3
Death 2/826 (0.2%) 2 3/822 (0.4%) 3 3/824 (0.4%) 3 2/825 (0.2%) 2
Device malfunction 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gait disturbance 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 2/825 (0.2%) 2
Generalised oedema 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hyperthermia malignant 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Impaired healing 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Metaplasia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Microlithiasis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Multi-organ failure 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 2/825 (0.2%) 2
Necrosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Non-cardiac chest pain 8/826 (1%) 8 5/822 (0.6%) 5 8/824 (1%) 8 4/825 (0.5%) 5
Oedema peripheral 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Pyrexia 1/826 (0.1%) 1 1/822 (0.1%) 1 2/824 (0.2%) 2 0/825 (0%) 0
Sudden cardiac death 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Sudden death 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Drug intolerance 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Oedema 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Hepatobiliary disorders
Bile duct stone 0/826 (0%) 0 2/822 (0.2%) 2 2/824 (0.2%) 2 1/825 (0.1%) 1
Biliary colic 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cholangitis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cholecystitis 0/826 (0%) 0 1/822 (0.1%) 1 4/824 (0.5%) 4 2/825 (0.2%) 2
Cholecystitis acute 3/826 (0.4%) 3 0/822 (0%) 0 6/824 (0.7%) 6 2/825 (0.2%) 2
Cholecystitis chronic 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cholelithiasis 4/826 (0.5%) 4 2/822 (0.2%) 2 4/824 (0.5%) 4 1/825 (0.1%) 1
Cholelithiasis obstructive 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cholestasis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Gallbladder necrosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Gallbladder polyp 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Hepatic cirrhosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Hepatic congestion 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hydrocholecystis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ischaemic hepatitis 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Jaundice 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hepatic failure 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pneumobilia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Immune system disorders
Anaphylactic shock 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Drug hypersensitivity 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hypersensitivity 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Sarcoidosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Infections and infestations
Abscess 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Abscess limb 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Acute hepatitis B 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Appendicitis 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Bacteraemia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Boutonneuse fever 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Bronchitis 2/826 (0.2%) 2 2/822 (0.2%) 2 4/824 (0.5%) 4 2/825 (0.2%) 2
Bronchopneumonia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Campylobacter gastroenteritis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Campylobacter infection 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cellulitis 6/826 (0.7%) 6 3/822 (0.4%) 3 7/824 (0.8%) 7 9/825 (1.1%) 10
Clostridium difficile colitis 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cystitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 2/825 (0.2%) 2
Dengue fever 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Device related sepsis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Diabetic foot infection 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Diverticulitis 1/826 (0.1%) 1 2/822 (0.2%) 2 2/824 (0.2%) 2 1/825 (0.1%) 1
Endocarditis 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Enteritis infectious 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Enterococcal infection 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Epididymitis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Escherichia infection 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Escherichia sepsis 1/826 (0.1%) 1 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Gangrene 2/826 (0.2%) 2 1/822 (0.1%) 1 4/824 (0.5%) 4 2/825 (0.2%) 2
Gastroenteritis 0/826 (0%) 0 2/822 (0.2%) 2 4/824 (0.5%) 4 2/825 (0.2%) 2
Gastroenteritis rotavirus 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 2 0/825 (0%) 0
Gastroenteritis salmonella 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gastroenteritis viral 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Herpes zoster 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Implant site infection 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Incision site infection 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Infected skin ulcer 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Infectious colitis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Infective exacerbation of chronic obstructive airways disease 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Influenza 1/826 (0.1%) 1 1/822 (0.1%) 1 2/824 (0.2%) 2 2/825 (0.2%) 2
Labyrinthitis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Liver abscess 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Lobar pneumonia 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Localised infection 1/826 (0.1%) 1 2/822 (0.2%) 2 2/824 (0.2%) 2 1/825 (0.1%) 2
Lower respiratory tract infection 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Meningitis bacterial 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Necrotising fasciitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Oesophageal candidiasis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Osteomyelitis 5/826 (0.6%) 5 1/822 (0.1%) 1 2/824 (0.2%) 2 3/825 (0.4%) 3
Otitis externa 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Paronychia 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Perirectal abscess 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Peritonitis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Peritonsillar abscess 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Periumbilical abscess 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pharyngitis 1/826 (0.1%) 1 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Pneumonia 18/826 (2.2%) 19 15/822 (1.8%) 16 22/824 (2.7%) 26 14/825 (1.7%) 14
Pneumonia pneumococcal 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Post procedural infection 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Post procedural pneumonia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Postoperative wound infection 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Pseudomembranous colitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Pulmonary sepsis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pyelonephritis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Pyelonephritis acute 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pyelonephritis chronic 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Respiratory tract infection viral 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Sepsis 7/826 (0.8%) 7 4/822 (0.5%) 4 3/824 (0.4%) 3 7/825 (0.8%) 7
Septic shock 1/826 (0.1%) 1 0/822 (0%) 0 4/824 (0.5%) 4 3/825 (0.4%) 3
Sinusitis 0/826 (0%) 0 1/822 (0.1%) 1 2/824 (0.2%) 2 1/825 (0.1%) 2
Soft tissue infection 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Splenic abscess 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Staphylococcal infection 2/826 (0.2%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Staphylococcal osteomyelitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Staphylococcal sepsis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Subcutaneous abscess 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Tooth abscess 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Tuberculosis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Upper respiratory tract infection 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 0/825 (0%) 0
Urinary tract infection 9/826 (1.1%) 9 2/822 (0.2%) 2 10/824 (1.2%) 10 6/825 (0.7%) 6
Urinary tract infection pseudomonal 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Urinary tract infection staphylococcal 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Urosepsis 2/826 (0.2%) 2 1/822 (0.1%) 1 2/824 (0.2%) 2 1/825 (0.1%) 1
Vestibular neuronitis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Viral infection 2/826 (0.2%) 2 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Abdominal sepsis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Aspergilloma 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Bronchitis bacterial 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Gastritis viral 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Groin abscess 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Laryngitis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pneumonia respiratory syncytial viral 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Respiratory tract infection 1/826 (0.1%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Septic encephalopathy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Staphylococcal bacteraemia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Wound infection bacterial 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Injury, poisoning and procedural complications
Accident at work 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Anaemia postoperative 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Animal bite 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ankle fracture 2/826 (0.2%) 2 0/822 (0%) 0 2/824 (0.2%) 2 0/825 (0%) 0
Contusion 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Dural tear 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Failure to anastomose 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Fall 11/826 (1.3%) 11 5/822 (0.6%) 5 11/824 (1.3%) 11 8/825 (1%) 8
Femur fracture 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Foot fracture 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hand fracture 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Head injury 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Humerus fracture 0/826 (0%) 0 2/822 (0.2%) 3 0/824 (0%) 0 1/825 (0.1%) 1
Incorrect dose administered 1/826 (0.1%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Injury 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Intentional overdose 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Laceration 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Limb injury 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Meniscus injury 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Muscle strain 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Overdose 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Post procedural haematoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Postoperative ileus 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Postoperative respiratory failure 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Radius fracture 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Rib fracture 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Road traffic accident 2/826 (0.2%) 2 4/822 (0.5%) 4 3/824 (0.4%) 3 4/825 (0.5%) 5
Scapula fracture 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Seroma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Skin abrasion 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Skull fracture 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Spinal compression fracture 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Subdural haematoma 1/826 (0.1%) 1 2/822 (0.2%) 2 1/824 (0.1%) 1 0/825 (0%) 0
Tendon rupture 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Thermal burn 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Toxicity to various agents 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 2 1/825 (0.1%) 1
Traumatic fracture 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Traumatic haemothorax 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Traumatic ulcer 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Vascular graft complication 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Vascular graft occlusion 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Vascular pseudoaneurysm 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Wound 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Wound necrosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Wrong drug administered 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Alcohol poisoning 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Burns third degree 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Cervical vertebral fracture 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Hip fracture 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Incisional hernia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Lumbar vertebral fracture 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Near drowning 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Investigations
Amylase increased 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Arteriogram coronary 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Bacterial test positive 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Blood alkaline phosphatase increased 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Blood bilirubin increased 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Blood creatinine increased 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Blood glucose fluctuation 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Blood glucose increased 1/826 (0.1%) 6 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Blood urea increased 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Catheterisation cardiac 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Ejection fraction decreased 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Electrocardiogram QT prolonged 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Electrocardiogram ST segment abnormal 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Electrocardiogram T wave inversion 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Electrocardiogram change 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Lipase increased 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Liver function test abnormal 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Pancreatic enzymes increased 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Transaminases increased 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Troponin increased 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Weight decreased 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Coagulation time prolonged 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Metabolism and nutrition disorders
Acidosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Dehydration 3/826 (0.4%) 3 5/822 (0.6%) 5 2/824 (0.2%) 2 0/825 (0%) 0
Diabetes mellitus 2/826 (0.2%) 2 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Diabetes mellitus inadequate control 4/826 (0.5%) 4 1/822 (0.1%) 1 5/824 (0.6%) 7 4/825 (0.5%) 5
Diabetic ketoacidosis 1/826 (0.1%) 2 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
Electrolyte imbalance 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Failure to thrive 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Fluid overload 2/826 (0.2%) 2 1/822 (0.1%) 1 1/824 (0.1%) 2 0/825 (0%) 0
Gout 1/826 (0.1%) 2 0/822 (0%) 0 0/824 (0%) 0 2/825 (0.2%) 2
Hyperglycaemia 3/826 (0.4%) 3 2/822 (0.2%) 2 4/824 (0.5%) 4 4/825 (0.5%) 4
Hyperkalaemia 0/826 (0%) 0 1/822 (0.1%) 1 3/824 (0.4%) 4 1/825 (0.1%) 1
Hypocalcaemia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Hypoglycaemia 7/826 (0.8%) 8 2/822 (0.2%) 2 5/824 (0.6%) 7 6/825 (0.7%) 6
Hypokalaemia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Hypomagnesaemia 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Hyponatraemia 1/826 (0.1%) 1 0/822 (0%) 0 4/824 (0.5%) 4 0/825 (0%) 0
Hypovolaemia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Lactic acidosis 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Obesity 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Metabolic acidosis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Metabolic disorder 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
Arthritis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
Back pain 1/826 (0.1%) 1 4/822 (0.5%) 4 1/824 (0.1%) 1 6/825 (0.7%) 6
Chondrolysis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Costochondritis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Diabetic arthropathy 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Fibromyalgia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Foot deformity 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Intervertebral disc disorder 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Intervertebral disc protrusion 3/826 (0.4%) 3 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Lumbar spinal stenosis 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
Muscle spasms 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Musculoskeletal chest pain 0/826 (0%) 0 2/822 (0.2%) 2 4/824 (0.5%) 5 3/825 (0.4%) 3
Musculoskeletal pain 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Neck pain 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Osteoarthritis 6/826 (0.7%) 7 8/822 (1%) 8 9/824 (1.1%) 9 10/825 (1.2%) 10
Osteonecrosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Pain in extremity 1/826 (0.1%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Rheumatoid arthritis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Spinal column stenosis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 4 0/825 (0%) 0
Spinal osteoarthritis 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Synovial cyst 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Flank pain 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Mobility decreased 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Muscular weakness 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Soft tissue disorder 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Acute myeloid leukaemia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Adenocarcinoma gastric 2/826 (0.2%) 2 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Adenocarcinoma of colon 1/826 (0.1%) 1 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
Adenocarcinoma pancreas 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Anaplastic astrocytoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
B-cell lymphoma 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 2/825 (0.2%) 2
B-cell small lymphocytic lymphoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Basal cell carcinoma 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Benign lymph node neoplasm 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Benign neoplasm of thyroid gland 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Bladder neoplasm 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Bladder papilloma 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Bladder transitional cell carcinoma 0/826 (0%) 0 1/822 (0.1%) 1 2/824 (0.2%) 2 1/825 (0.1%) 1
Bladder transitional cell carcinoma recurrent 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Bladder transitional cell carcinoma stage II 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Bone cancer metastatic 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Breast cancer 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Breast cancer in situ 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Breast cancer stage III 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Bronchial carcinoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Cholangiocarcinoma 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 2 0/825 (0%) 0
Cholesteatoma 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 1/825 (0.1%) 1
Choroid melanoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Chronic lymphocytic leukaemia 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Clear cell renal cell carcinoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Colon adenoma 0/826 (0%) 0 4/822 (0.5%) 4 0/824 (0%) 0 0/825 (0%) 0
Colon cancer 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Colon cancer metastatic 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Colon neoplasm 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Colorectal cancer 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Endometrial adenocarcinoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Endometrial sarcoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Extranodal marginal zone B-cell lymphoma (MALT type) 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Gallbladder adenocarcinoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Gastric cancer 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Glomus tumour 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Growth hormone-producing pituitary tumour 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Hepatic adenoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Hepatic cancer 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Invasive ductal breast carcinoma 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 0/825 (0%) 0
Laryngeal squamous cell carcinoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Lip neoplasm malignant stage unspecified 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Lung adenocarcinoma 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Lung adenocarcinoma stage IV 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Lung carcinoma cell type unspecified stage IV 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Lung neoplasm 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Lung neoplasm malignant 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Malignant melanoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Metastases to central nervous system 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Metastases to liver 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Metastases to lung 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Metastases to lymph nodes 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Metastatic gastric cancer 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Neoplasm of appendix 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Non-small cell lung cancer 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Ovarian epithelial cancer 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ovarian germ cell teratoma benign 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Pancreatic carcinoma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pancreatic carcinoma metastatic 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Papillary thyroid cancer 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Paraganglion neoplasm 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Parathyroid tumour benign 0/826 (0%) 0 1/822 (0.1%) 1 2/824 (0.2%) 2 2/825 (0.2%) 2
Phaeochromocytoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Plasma cell myeloma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Prostate cancer 3/826 (0.4%) 3 3/822 (0.4%) 3 4/824 (0.5%) 4 1/825 (0.1%) 1
Prostate cancer metastatic 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Prostate cancer recurrent 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Prostate cancer stage I 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Prostate cancer stage III 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Rectal cancer 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Renal cancer metastatic 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Renal cancer stage I 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Renal cell carcinoma 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Small cell lung cancer 0/826 (0%) 0 2/822 (0.2%) 2 2/824 (0.2%) 2 0/825 (0%) 0
Squamous cell carcinoma 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Squamous cell carcinoma of lung 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Squamous cell carcinoma of skin 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Thyroid neoplasm 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Transitional cell carcinoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Ureteric cancer 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Uterine leiomyoma 0/826 (0%) 0 2/822 (0.2%) 2 0/824 (0%) 0 1/825 (0.1%) 1
Brain neoplasm 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Chondroma 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Invasive breast carcinoma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Lung adenocarcinoma stage 0 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Metastases to bone 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Pancreatic carcinoma stage IV 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Thyroid cancer metastatic 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Nervous system disorders
Brain oedema 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Brain stem infarction 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Carotid artery stenosis 0/826 (0%) 0 0/822 (0%) 0 3/824 (0.4%) 3 3/825 (0.4%) 3
Cerebellar haemorrhage 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cerebellar syndrome 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cerebral haemorrhage 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cerebral infarction 2/826 (0.2%) 2 2/822 (0.2%) 3 3/824 (0.4%) 3 0/825 (0%) 0
Cerebral ischaemia 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cerebrospinal fluid leakage 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Cerebrovascular accident 3/826 (0.4%) 3 3/822 (0.4%) 3 6/824 (0.7%) 6 6/825 (0.7%) 8
Cerebrovascular disorder 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Cervical myelopathy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cervical radiculopathy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Chronic inflammatory demyelinating polyradiculoneuropathy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Coma 0/826 (0%) 0 2/822 (0.2%) 3 0/824 (0%) 0 0/825 (0%) 0
Coordination abnormal 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Diabetic mononeuropathy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Dizziness 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 2 1/825 (0.1%) 1
Embolic stroke 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Epilepsy 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Haemorrhage intracranial 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Haemorrhagic stroke 1/826 (0.1%) 1 1/822 (0.1%) 1 4/824 (0.5%) 4 1/825 (0.1%) 1
Headache 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Hepatic encephalopathy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hydrocephalus 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hypertensive encephalopathy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Hypoaesthesia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Hypoglycaemic unconsciousness 5/826 (0.6%) 5 3/822 (0.4%) 3 1/824 (0.1%) 1 3/825 (0.4%) 6
Hypoxic-ischaemic encephalopathy 1/826 (0.1%) 2 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Intracranial aneurysm 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Intracranial hypotension 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Intraventricular haemorrhage 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Ischaemic cerebral infarction 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Ischaemic stroke 8/826 (1%) 8 7/822 (0.9%) 8 16/824 (1.9%) 16 4/825 (0.5%) 4
Lacunar infarction 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Loss of consciousness 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Metabolic encephalopathy 2/826 (0.2%) 2 0/822 (0%) 0 2/824 (0.2%) 2 0/825 (0%) 0
Migraine 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Movement disorder 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Multiple sclerosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Neuralgia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Parkinsonism 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Presyncope 0/826 (0%) 0 2/822 (0.2%) 2 2/824 (0.2%) 2 1/825 (0.1%) 1
Radiculitis lumbosacral 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Radiculopathy 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Seizure 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 3/825 (0.4%) 3
Syncope 2/826 (0.2%) 2 4/822 (0.5%) 4 3/824 (0.4%) 4 3/825 (0.4%) 3
Thalamic infarction 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Transient ischaemic attack 7/826 (0.8%) 8 6/822 (0.7%) 7 10/824 (1.2%) 10 7/825 (0.8%) 7
VIIth nerve paralysis 1/826 (0.1%) 1 0/822 (0%) 0 2/824 (0.2%) 2 1/825 (0.1%) 1
VIth nerve disorder 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Vascular parkinsonism 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Visual field defect 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Carotid artery occlusion 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Cranial nerve disorder 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hypoglycaemic coma 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Myelitis transverse 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Speech disorder 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Psychiatric disorders
Anxiety 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Confusional state 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Delirium 0/826 (0%) 0 2/822 (0.2%) 2 1/824 (0.1%) 1 1/825 (0.1%) 1
Depression 1/826 (0.1%) 1 2/822 (0.2%) 2 3/824 (0.4%) 3 0/825 (0%) 0
Mental status changes 1/826 (0.1%) 1 0/822 (0%) 0 2/824 (0.2%) 2 3/825 (0.4%) 3
Post-traumatic stress disorder 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Schizoaffective disorder 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Sleep terror 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Homicidal ideation 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Renal and urinary disorders
Acute kidney injury 18/826 (2.2%) 22 6/822 (0.7%) 8 14/824 (1.7%) 14 22/825 (2.7%) 24
Acute prerenal failure 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Azotaemia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Bladder trabeculation 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Calculus ureteric 3/826 (0.4%) 3 3/822 (0.4%) 3 2/824 (0.2%) 2 1/825 (0.1%) 1
Calculus urinary 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Chronic kidney disease 10/826 (1.2%) 10 5/822 (0.6%) 5 14/824 (1.7%) 17 5/825 (0.6%) 5
Dysuria 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Glomerulonephritis chronic 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Haematuria 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Hydronephrosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Nephrolithiasis 2/826 (0.2%) 2 3/822 (0.4%) 3 1/824 (0.1%) 1 3/825 (0.4%) 3
Nephropathy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Nephrotic syndrome 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 2 0/825 (0%) 0
Proteinuria 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Renal artery arteriosclerosis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Renal colic 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Renal cyst 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Renal failure 2/826 (0.2%) 2 3/822 (0.4%) 3 1/824 (0.1%) 1 1/825 (0.1%) 1
Renal impairment 3/826 (0.4%) 3 1/822 (0.1%) 1 3/824 (0.4%) 3 1/825 (0.1%) 1
Stag horn calculus 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Urethral stenosis 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Urinary bladder polyp 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Urinary incontinence 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Urinary retention 2/826 (0.2%) 3 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Anuria 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Diabetic end stage renal disease 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Renal artery stenosis 0/826 (0%) 0 1/822 (0.1%) 2 0/824 (0%) 0 0/825 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 3/826 (0.4%) 3 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Cystocele 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Endometrial hyperplasia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Epididymal tenderness 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Erectile dysfunction 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Menorrhagia 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Ovarian cyst 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Prostatic obstruction 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Prostatomegaly 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Testicular cyst 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Uterine polyp 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Vaginal prolapse 0/826 (0%) 0 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Breast cyst 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Genital haemorrhage 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acquired diaphragmatic eventration 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Acute pulmonary oedema 3/826 (0.4%) 3 2/822 (0.2%) 2 0/824 (0%) 0 2/825 (0.2%) 2
Acute respiratory failure 3/826 (0.4%) 3 1/822 (0.1%) 1 3/824 (0.4%) 3 1/825 (0.1%) 1
Asthma 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Atelectasis 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Chronic obstructive pulmonary disease 3/826 (0.4%) 6 5/822 (0.6%) 5 7/824 (0.8%) 7 7/825 (0.8%) 9
Dyspnoea 6/826 (0.7%) 6 5/822 (0.6%) 5 3/824 (0.4%) 3 4/825 (0.5%) 4
Dyspnoea at rest 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Epistaxis 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Haemoptysis 0/826 (0%) 0 1/822 (0.1%) 3 0/824 (0%) 0 0/825 (0%) 0
Hydrothorax 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hypoxia 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Laryngeal stenosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Pleural effusion 1/826 (0.1%) 1 1/822 (0.1%) 1 2/824 (0.2%) 3 0/825 (0%) 0
Pleurisy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pneumonia aspiration 0/826 (0%) 0 2/822 (0.2%) 3 0/824 (0%) 0 0/825 (0%) 0
Pneumothorax 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Pulmonary congestion 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Pulmonary embolism 2/826 (0.2%) 2 4/822 (0.5%) 4 3/824 (0.4%) 3 4/825 (0.5%) 4
Pulmonary hypertension 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Pulmonary mass 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Pulmonary oedema 2/826 (0.2%) 2 1/822 (0.1%) 1 2/824 (0.2%) 2 5/825 (0.6%) 6
Respiratory arrest 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Respiratory distress 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Respiratory failure 2/826 (0.2%) 2 3/822 (0.4%) 3 3/824 (0.4%) 3 3/825 (0.4%) 3
Bronchitis chronic 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Bronchospasm 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hyperventilation 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Idiopathic pulmonary fibrosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Lung cyst 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Skin and subcutaneous tissue disorders
Actinic keratosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Angioedema 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Decubitus ulcer 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Diabetic foot 6/826 (0.7%) 8 2/822 (0.2%) 2 3/824 (0.4%) 3 5/825 (0.6%) 8
Hyperkeratosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Pruritus 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Psoriasis 1/826 (0.1%) 2 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Rash papular 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Skin necrosis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Skin ulcer 3/826 (0.4%) 3 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 2
Stevens-Johnson syndrome 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Surgical and medical procedures
Abdominal hernia repair 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Angioplasty 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Brachytherapy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Carotid angioplasty 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Carotid artery stent insertion 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Carotid endarterectomy 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 4/825 (0.5%) 4
Carotid revascularisation 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Cataract operation 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 2/825 (0.2%) 2
Coronary angioplasty 1/826 (0.1%) 1 1/822 (0.1%) 1 4/824 (0.5%) 4 5/825 (0.6%) 5
Coronary arterial stent insertion 15/826 (1.8%) 19 8/822 (1%) 9 17/824 (2.1%) 18 17/825 (2.1%) 19
Coronary artery bypass 8/826 (1%) 8 5/822 (0.6%) 5 14/824 (1.7%) 14 10/825 (1.2%) 10
Coronary revascularisation 11/826 (1.3%) 12 10/822 (1.2%) 10 15/824 (1.8%) 17 9/825 (1.1%) 10
Hospitalisation 1/826 (0.1%) 1 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Laparotomy 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Mechanical ventilation 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Nasal polypectomy 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Percutaneous coronary intervention 2/826 (0.2%) 2 1/822 (0.1%) 1 3/824 (0.4%) 4 6/825 (0.7%) 7
Peripheral artery angioplasty 2/826 (0.2%) 2 1/822 (0.1%) 1 0/824 (0%) 0 2/825 (0.2%) 2
Peripheral artery bypass 1/826 (0.1%) 1 1/822 (0.1%) 1 1/824 (0.1%) 1 0/825 (0%) 0
Peripheral artery stent insertion 1/826 (0.1%) 1 3/822 (0.4%) 3 0/824 (0%) 0 0/825 (0%) 0
Peripheral endarterectomy 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Peripheral revascularisation 2/826 (0.2%) 2 4/822 (0.5%) 4 5/824 (0.6%) 5 9/825 (1.1%) 9
Pterygium operation 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Removal of internal fixation 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Stent placement 2/826 (0.2%) 2 2/822 (0.2%) 2 1/824 (0.1%) 1 1/825 (0.1%) 2
Umbilical hernia repair 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Renal artery stent placement 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Tendon sheath incision 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Vascular disorders
Aortic aneurysm 1/826 (0.1%) 1 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Aortic dissection 0/826 (0%) 0 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Aortic stenosis 2/826 (0.2%) 2 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Arterial insufficiency 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Circulatory collapse 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Deep vein thrombosis 1/826 (0.1%) 1 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Extremity necrosis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 1/825 (0.1%) 1
Femoral artery occlusion 1/826 (0.1%) 1 2/822 (0.2%) 2 0/824 (0%) 0 0/825 (0%) 0
Haematoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hypertension 1/826 (0.1%) 1 1/822 (0.1%) 1 3/824 (0.4%) 3 3/825 (0.4%) 3
Hypertensive crisis 3/826 (0.4%) 3 1/822 (0.1%) 1 0/824 (0%) 0 2/825 (0.2%) 2
Hypertensive emergency 4/826 (0.5%) 4 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Hypotension 2/826 (0.2%) 2 0/822 (0%) 0 3/824 (0.4%) 3 3/825 (0.4%) 3
Intra-abdominal haematoma 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Orthostatic hypotension 2/826 (0.2%) 2 1/822 (0.1%) 1 0/824 (0%) 0 1/825 (0.1%) 1
Peripheral arterial occlusive disease 3/826 (0.4%) 3 2/822 (0.2%) 2 1/824 (0.1%) 1 3/825 (0.4%) 3
Peripheral artery aneurysm 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Peripheral artery stenosis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 1/825 (0.1%) 1
Peripheral artery thrombosis 0/826 (0%) 0 1/822 (0.1%) 1 2/824 (0.2%) 2 0/825 (0%) 0
Peripheral ischaemia 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Peripheral vascular disorder 0/826 (0%) 0 0/822 (0%) 0 2/824 (0.2%) 2 3/825 (0.4%) 3
Shock haemorrhagic 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Temporal arteritis 1/826 (0.1%) 1 0/822 (0%) 0 0/824 (0%) 0 0/825 (0%) 0
Varicose vein 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Vasculitis 0/826 (0%) 0 0/822 (0%) 0 1/824 (0.1%) 1 0/825 (0%) 0
Femoral artery aneurysm 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Leriche syndrome 0/826 (0%) 0 1/822 (0.1%) 1 0/824 (0%) 0 0/825 (0%) 0
Other (Not Including Serious) Adverse Events
Semaglutide 0.5 mg Semaglutide 1.0 mg Placebo 0.5 mg Placebo 1.0 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 573/826 (69.4%) 587/822 (71.4%) 547/824 (66.4%) 524/825 (63.5%)
Blood and lymphatic system disorders
Anaemia 41/826 (5%) 46 33/822 (4%) 34 44/824 (5.3%) 46 48/825 (5.8%) 55
Eye disorders
Cataract 55/826 (6.7%) 59 43/822 (5.2%) 48 37/824 (4.5%) 38 45/825 (5.5%) 46
Diabetic retinopathy 46/826 (5.6%) 50 56/822 (6.8%) 63 39/824 (4.7%) 39 38/825 (4.6%) 43
Gastrointestinal disorders
Abdominal pain 45/826 (5.4%) 54 35/822 (4.3%) 40 33/824 (4%) 37 31/825 (3.8%) 36
Abdominal pain upper 35/826 (4.2%) 37 42/822 (5.1%) 53 19/824 (2.3%) 22 19/825 (2.3%) 33
Constipation 46/826 (5.6%) 52 79/822 (9.6%) 97 37/824 (4.5%) 42 36/825 (4.4%) 38
Diarrhoea 148/826 (17.9%) 277 148/822 (18%) 245 97/824 (11.8%) 159 87/825 (10.5%) 112
Dyspepsia 51/826 (6.2%) 68 63/822 (7.7%) 88 23/824 (2.8%) 25 18/825 (2.2%) 19
Nausea 143/826 (17.3%) 233 179/822 (21.8%) 282 62/824 (7.5%) 78 66/825 (8%) 94
Vomiting 87/826 (10.5%) 128 122/822 (14.8%) 170 42/824 (5.1%) 51 33/825 (4%) 41
General disorders
Fatigue 24/826 (2.9%) 27 42/822 (5.1%) 48 15/824 (1.8%) 16 26/825 (3.2%) 28
Infections and infestations
Bronchitis 46/826 (5.6%) 52 38/822 (4.6%) 43 49/824 (5.9%) 52 51/825 (6.2%) 64
Influenza 51/826 (6.2%) 60 48/822 (5.8%) 56 48/824 (5.8%) 57 46/825 (5.6%) 63
Nasopharyngitis 66/826 (8%) 91 60/822 (7.3%) 77 78/824 (9.5%) 99 66/825 (8%) 84
Upper respiratory tract infection 53/826 (6.4%) 59 51/822 (6.2%) 64 63/824 (7.6%) 75 65/825 (7.9%) 88
Urinary tract infection 78/826 (9.4%) 108 71/822 (8.6%) 93 64/824 (7.8%) 97 68/825 (8.2%) 87
Investigations
Amylase increased 31/826 (3.8%) 39 48/822 (5.8%) 57 28/824 (3.4%) 33 28/825 (3.4%) 33
Lipase increased 94/826 (11.4%) 121 90/822 (10.9%) 123 66/824 (8%) 76 69/825 (8.4%) 83
Metabolism and nutrition disorders
Decreased appetite 86/826 (10.4%) 97 75/822 (9.1%) 88 19/824 (2.3%) 21 9/825 (1.1%) 10
Musculoskeletal and connective tissue disorders
Arthralgia 41/826 (5%) 45 35/822 (4.3%) 40 57/824 (6.9%) 69 58/825 (7%) 70
Back pain 54/826 (6.5%) 54 49/822 (6%) 58 49/824 (5.9%) 59 48/825 (5.8%) 50
Pain in extremity 38/826 (4.6%) 42 29/822 (3.5%) 31 46/824 (5.6%) 51 42/825 (5.1%) 45
Nervous system disorders
Dizziness 53/826 (6.4%) 57 46/822 (5.6%) 54 38/824 (4.6%) 53 38/825 (4.6%) 45
Headache 54/826 (6.5%) 77 58/822 (7.1%) 89 67/824 (8.1%) 114 74/825 (9%) 110
Renal and urinary disorders
Microalbuminuria 27/826 (3.3%) 30 33/822 (4%) 35 46/824 (5.6%) 51 42/825 (5.1%) 45
Respiratory, thoracic and mediastinal disorders
Cough 36/826 (4.4%) 41 32/822 (3.9%) 33 40/824 (4.9%) 41 46/825 (5.6%) 48

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.

Results Point of Contact

Name/Title Global Clinical Registry (GCR, 1452)
Organization Novo Nordisk A/S
Phone
Email clinicaltrials@novonordisk.com
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01720446
Other Study ID Numbers:
  • NN9535-3744
  • 2012-002839-28
  • U1111-1131-7227
First Posted:
Nov 2, 2012
Last Update Posted:
Jun 27, 2019
Last Verified:
Jun 1, 2019