DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01959529
• Collaborator: (none)
• Enrollment: 7,637
• Locations: 446
• Arms: 2
• Actual Duration (Months): 35.6
• Patients Per Site: 17.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to compare cardiovascular safety of insulin degludec versus insulin glargine in subjects with type 2 diabetes at high risk of cardiovascular events.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin degludec; Drug: insulin glargine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 7637 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events
• Actual Study Start Date: Oct 29, 2013
• Actual Primary Completion Date: Oct 16, 2016
• Actual Study Completion Date: Oct 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec (IDeg) All subjects will continue their current antidiabetic therapy except for the basal insulin component (if any) that will be replaced by the investigational product.	Drug: insulin degludec; Injected once daily subcutaneously (s.c., under the skin)
Active Comparator: Insulin glargine (IGlar) All subjects will continue their current antidiabetic therapy except for the basal insulin component (if any) that will be replaced by the investigational product.	Drug: insulin glargine; Injected once daily subcutaneously (s.c., under the skin)

Outcome Measures

Primary Outcome Measures

1. Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke [From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)]

   Time from randomisation to first occurrence of an event adjudication committee (EAC)-confirmed 3-component major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction, or nonfatal stroke. Events with EAC-confirmed onset date between randomisation and individual end of trial were included in the analyses. The number of subjects experiencing first EAC-confirmed MACEs, date between randomisation to the end of trial, both days included were presented. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.

Secondary Outcome Measures

1. Number of EAC-confirmed Severe Hypoglycaemic Episodes [From randomisation to individual end of trial (maximum patient year observation: 2.75 years)]

   Number of severe hypoglycaemic episodes from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.

2. Occurrence of at Least One EAC Confirmed Severe Hypoglycaemic Episode Within a Subject (Yes/no) [From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)]

   Occurrence of at least one EAC-confirmed severe hypoglycaemic episode within a subject from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions.

3. Change in Glycosylated Haemoglobin (HbA1c) [Randomisation to 24 months]

   Mean change in HbA1c from week 0 to month 24.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Type 2 diabetes - Age above or equal to 50 years with predefined previous cardiovascular disease(s) or renal disease or age above or equal to 60 years with predefined cardiovascular risk factors - HbA1c (glycosylated haemoglobin) above or equal to 7.0% or HbA1c below 7.0% and current insulin treatment corresponding to above or equal to 20 U of basal insulin per day - One or more oral or injectable antidiabetic agent(s) Exclusion Criteria: - An acute coronary or cerebrovascular event in the previous 60 days - Planned coronary, carotid or peripheral artery revascularisation - Chronic heart failure NYHA (New York Heart Association) class IV - Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell skin carcinoma)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35216
2	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
3	Novo Nordisk Investigational Site	Montgomery	Alabama	United States	36106
4	Novo Nordisk Investigational Site	Montgomery	Alabama	United States	36109
5	Novo Nordisk Investigational Site	Gilbert	Arizona	United States	85295
6	Novo Nordisk Investigational Site	Glendale	Arizona	United States	85308
7	Novo Nordisk Investigational Site	Litchfield Park	Arizona	United States	85340
8	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85050
9	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85704
10	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85714
11	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85723
12	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72205-5446
13	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72205
14	Novo Nordisk Investigational Site	Searcy	Arkansas	United States	72143
15	Novo Nordisk Investigational Site	Chula Vista	California	United States	91910
16	Novo Nordisk Investigational Site	Concord	California	United States	94520
17	Novo Nordisk Investigational Site	Downey	California	United States	90242
18	Novo Nordisk Investigational Site	Duarte	California	United States	91010
19	Novo Nordisk Investigational Site	Encino	California	United States	91436
20	Novo Nordisk Investigational Site	Fresno	California	United States	93720
21	Novo Nordisk Investigational Site	Greenbrae	California	United States	94904
22	Novo Nordisk Investigational Site	Huntington Beach	California	United States	92648
23	Novo Nordisk Investigational Site	Inglewood	California	United States	90301
24	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
25	Novo Nordisk Investigational Site	La Mesa	California	United States	91942
26	Novo Nordisk Investigational Site	Lancaster	California	United States	93534
27	Novo Nordisk Investigational Site	Long Beach	California	United States	90822
28	Novo Nordisk Investigational Site	Los Alamitos	California	United States	90720
29	Novo Nordisk Investigational Site	Mission Hills	California	United States	91345
30	Novo Nordisk Investigational Site	Montclair	California	United States	91763
31	Novo Nordisk Investigational Site	Monterey	California	United States	93940
32	Novo Nordisk Investigational Site	North Hollywood	California	United States	91606
33	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
34	Novo Nordisk Investigational Site	Poway	California	United States	92064
35	Novo Nordisk Investigational Site	San Diego	California	United States	92111
36	Novo Nordisk Investigational Site	San Diego	California	United States	92120
37	Novo Nordisk Investigational Site	San Ramon	California	United States	94583
38	Novo Nordisk Investigational Site	Santa Ana	California	United States	92704
39	Novo Nordisk Investigational Site	Sherman Oaks	California	United States	91403
40	Novo Nordisk Investigational Site	Thousand Oaks	California	United States	91360
41	Novo Nordisk Investigational Site	Tustin	California	United States	92780
42	Novo Nordisk Investigational Site	Ventura	California	United States	93003
43	Novo Nordisk Investigational Site	Vista	California	United States	92083
44	Novo Nordisk Investigational Site	Westminster	California	United States	92683
45	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80909
46	Novo Nordisk Investigational Site	Denver	Colorado	United States	80220
47	Novo Nordisk Investigational Site	Denver	Colorado	United States	80246
48	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
49	Novo Nordisk Investigational Site	Danbury	Connecticut	United States	06810
50	Novo Nordisk Investigational Site	Norwalk	Connecticut	United States	06851
51	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06708
52	Novo Nordisk Investigational Site	Boca Raton	Florida	United States	33433
53	Novo Nordisk Investigational Site	Boynton Beach	Florida	United States	33472
54	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
55	Novo Nordisk Investigational Site	Brandon	Florida	United States	33511
56	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33756
57	Novo Nordisk Investigational Site	Cooper City	Florida	United States	33024
58	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32003
59	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33316
60	Novo Nordisk Investigational Site	Gainesville	Florida	United States	32610
61	Novo Nordisk Investigational Site	Green Cove Springs	Florida	United States	32043
62	Novo Nordisk Investigational Site	Hialeah	Florida	United States	33012
63	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
64	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
65	Novo Nordisk Investigational Site	Miami	Florida	United States	33135
66	Novo Nordisk Investigational Site	Miami	Florida	United States	33136
67	Novo Nordisk Investigational Site	Miami	Florida	United States	33155
68	Novo Nordisk Investigational Site	Miami	Florida	United States	33165
69	Novo Nordisk Investigational Site	Miami	Florida	United States	33183
70	Novo Nordisk Investigational Site	Naples	Florida	United States	34119
71	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
72	Novo Nordisk Investigational Site	Orlando	Florida	United States	32806
73	Novo Nordisk Investigational Site	Panama City	Florida	United States	32401
74	Novo Nordisk Investigational Site	Ponte Vedra	Florida	United States	32081
75	Novo Nordisk Investigational Site	Port Charlotte	Florida	United States	33952
76	Novo Nordisk Investigational Site	Port Orange	Florida	United States	32127
77	Novo Nordisk Investigational Site	South Miami	Florida	United States	33143
78	Novo Nordisk Investigational Site	Tampa	Florida	United States	33619
79	Novo Nordisk Investigational Site	Tampa	Florida	United States	33624
80	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30339
81	Novo Nordisk Investigational Site	Decatur	Georgia	United States	30033
82	Novo Nordisk Investigational Site	Dunwoody	Georgia	United States	30338
83	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
84	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
85	Novo Nordisk Investigational Site	Savannah	Georgia	United States	31406
86	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
87	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
88	Novo Nordisk Investigational Site	Addison	Illinois	United States	60101
89	Novo Nordisk Investigational Site	Champaign	Illinois	United States	61821
90	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
91	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60616
92	Novo Nordisk Investigational Site	Crystal Lake	Illinois	United States	60012
93	Novo Nordisk Investigational Site	Gurnee	Illinois	United States	60031
94	Novo Nordisk Investigational Site	Hines	Illinois	United States	60141
95	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62702
96	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62711
97	Novo Nordisk Investigational Site	Brownsburg	Indiana	United States	46112
98	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
99	Novo Nordisk Investigational Site	Franklin	Indiana	United States	46131
100	Novo Nordisk Investigational Site	Greenfield	Indiana	United States	46140
101	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46254
102	Novo Nordisk Investigational Site	Michigan City	Indiana	United States	46360
103	Novo Nordisk Investigational Site	Muncie	Indiana	United States	47304
104	Novo Nordisk Investigational Site	Council Bluffs	Iowa	United States	51501
105	Novo Nordisk Investigational Site	Wichita	Kansas	United States	67205
106	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40502
107	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
108	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40206
109	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
110	Novo Nordisk Investigational Site	Madisonville	Kentucky	United States	42431
111	Novo Nordisk Investigational Site	Monroe	Louisiana	United States	71203
112	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70119
113	Novo Nordisk Investigational Site	Shreveport	Louisiana	United States	71103
114	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
115	Novo Nordisk Investigational Site	Bangor	Maine	United States	04401
116	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
117	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
118	Novo Nordisk Investigational Site	Watertown	Massachusetts	United States	02472
119	Novo Nordisk Investigational Site	Worcester	Massachusetts	United States	01655
120	Novo Nordisk Investigational Site	Ann Arbor	Michigan	United States	48105
121	Novo Nordisk Investigational Site	Ann Arbor	Michigan	United States	48106
122	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
123	Novo Nordisk Investigational Site	Detroit	Michigan	United States	48201
124	Novo Nordisk Investigational Site	Detroit	Michigan	United States	48202
125	Novo Nordisk Investigational Site	Kalamazoo	Michigan	United States	49009
126	Novo Nordisk Investigational Site	Livonia	Michigan	United States	48152
127	Novo Nordisk Investigational Site	Troy	Michigan	United States	48098
128	Novo Nordisk Investigational Site	Olive Branch	Mississippi	United States	38654
129	Novo Nordisk Investigational Site	Hazelwood	Missouri	United States	63042
130	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
131	Novo Nordisk Investigational Site	Kansas City	Missouri	United States	64111
132	Novo Nordisk Investigational Site	Billings	Montana	United States	59101
133	Novo Nordisk Investigational Site	Kalispell	Montana	United States	59901
134	Novo Nordisk Investigational Site	Elkhorn	Nebraska	United States	68022
135	Novo Nordisk Investigational Site	Fremont	Nebraska	United States	68025
136	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68105
137	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68114
138	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68124
139	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68144
140	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68198-4120
141	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89120
142	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89128
143	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
144	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
145	Novo Nordisk Investigational Site	East Brunswick	New Jersey	United States	08816
146	Novo Nordisk Investigational Site	Hoboken	New Jersey	United States	07030
147	Novo Nordisk Investigational Site	Albany	New York	United States	12206
148	Novo Nordisk Investigational Site	Lake Success	New York	United States	11042
149	Novo Nordisk Investigational Site	Mineola	New York	United States	11501
150	Novo Nordisk Investigational Site	New Windsor	New York	United States	12553
151	Novo Nordisk Investigational Site	New York	New York	United States	10029
152	Novo Nordisk Investigational Site	North Massapequa	New York	United States	11758-1802
153	Novo Nordisk Investigational Site	Northport	New York	United States	11768
154	Novo Nordisk Investigational Site	Rochester	New York	United States	14607
155	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
156	Novo Nordisk Investigational Site	Westfield	New York	United States	14787
157	Novo Nordisk Investigational Site	Asheville	North Carolina	United States	28801
158	Novo Nordisk Investigational Site	Asheville	North Carolina	United States	28803
159	Novo Nordisk Investigational Site	Burlington	North Carolina	United States	27215
160	Novo Nordisk Investigational Site	Cary	North Carolina	United States	27518
161	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27517
162	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28209
163	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
164	Novo Nordisk Investigational Site	Lexington	North Carolina	United States	27292
165	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557
166	Novo Nordisk Investigational Site	New Bern	North Carolina	United States	28562
167	Novo Nordisk Investigational Site	Statesville	North Carolina	United States	28625
168	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
169	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
170	Novo Nordisk Investigational Site	Winston-Salem	North Carolina	United States	27103
171	Novo Nordisk Investigational Site	Fargo	North Dakota	United States	58104
172	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45236
173	Novo Nordisk Investigational Site	Cleveland	Ohio	United States	44106-1702
174	Novo Nordisk Investigational Site	Cleveland	Ohio	United States	44121
175	Novo Nordisk Investigational Site	Cleveland	Ohio	United States	44195
176	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43235
177	Novo Nordisk Investigational Site	Delaware	Ohio	United States	43015
178	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
179	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
180	Novo Nordisk Investigational Site	Mentor	Ohio	United States	44060
181	Novo Nordisk Investigational Site	Perrysburg	Ohio	United States	43551
182	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
183	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104
184	Novo Nordisk Investigational Site	Portland	Oregon	United States	97239-3098
185	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
186	Novo Nordisk Investigational Site	Beaver	Pennsylvania	United States	15009
187	Novo Nordisk Investigational Site	Danville	Pennsylvania	United States	17822
188	Novo Nordisk Investigational Site	Hermitage	Pennsylvania	United States	16148
189	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19107
190	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19114
191	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15212
192	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15243
193	Novo Nordisk Investigational Site	Smithfield	Pennsylvania	United States	15478
194	Novo Nordisk Investigational Site	Uniontown	Pennsylvania	United States	15401
195	Novo Nordisk Investigational Site	Upper Darby	Pennsylvania	United States	19082
196	Novo Nordisk Investigational Site	Wilkes-Barre	Pennsylvania	United States	18702
197	Novo Nordisk Investigational Site	Anderson	South Carolina	United States	29621
198	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
199	Novo Nordisk Investigational Site	Moncks Corner	South Carolina	United States	29461
200	Novo Nordisk Investigational Site	Murrells Inlet	South Carolina	United States	29576
201	Novo Nordisk Investigational Site	Myrtle Beach	South Carolina	United States	29572
202	Novo Nordisk Investigational Site	Orangeburg	South Carolina	United States	29118
203	Novo Nordisk Investigational Site	Spartanburg	South Carolina	United States	29303
204	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404-1192
205	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
206	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
207	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
208	Novo Nordisk Investigational Site	Knoxville	Tennessee	United States	37938
209	Novo Nordisk Investigational Site	Memphis	Tennessee	United States	38119
210	Novo Nordisk Investigational Site	Memphis	Tennessee	United States	38163
211	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37203
212	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37208
213	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37212
214	Novo Nordisk Investigational Site	Tullahoma	Tennessee	United States	37388
215	Novo Nordisk Investigational Site	Arlington	Texas	United States	76012
216	Novo Nordisk Investigational Site	Austin	Texas	United States	78705
217	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
218	Novo Nordisk Investigational Site	Austin	Texas	United States	78749
219	Novo Nordisk Investigational Site	Carrollton	Texas	United States	75007
220	Novo Nordisk Investigational Site	Carrollton	Texas	United States	75010
221	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78404
222	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
223	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
224	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
225	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
226	Novo Nordisk Investigational Site	Fort Worth	Texas	United States	76117
227	Novo Nordisk Investigational Site	Fort Worth	Texas	United States	76132
228	Novo Nordisk Investigational Site	Houston	Texas	United States	77008
229	Novo Nordisk Investigational Site	Houston	Texas	United States	77024
230	Novo Nordisk Investigational Site	Houston	Texas	United States	77029
231	Novo Nordisk Investigational Site	Houston	Texas	United States	77060
232	Novo Nordisk Investigational Site	Houston	Texas	United States	77061
233	Novo Nordisk Investigational Site	Houston	Texas	United States	77070
234	Novo Nordisk Investigational Site	Houston	Texas	United States	77093
235	Novo Nordisk Investigational Site	Houston	Texas	United States	77099
236	Novo Nordisk Investigational Site	Humble	Texas	United States	77338
237	Novo Nordisk Investigational Site	Hurst	Texas	United States	76054
238	Novo Nordisk Investigational Site	Irving	Texas	United States	75039
239	Novo Nordisk Investigational Site	Lewisville	Texas	United States	75067
240	Novo Nordisk Investigational Site	Longview	Texas	United States	75605
241	Novo Nordisk Investigational Site	Lubbock	Texas	United States	79423
242	Novo Nordisk Investigational Site	Midland	Texas	United States	79707
243	Novo Nordisk Investigational Site	Odessa	Texas	United States	79761
244	Novo Nordisk Investigational Site	Pearland	Texas	United States	77584
245	Novo Nordisk Investigational Site	Richardson	Texas	United States	75080
246	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
247	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78215
248	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78228-6205
249	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78229
250	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78258
251	Novo Nordisk Investigational Site	Splendora	Texas	United States	77372
252	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
253	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
254	Novo Nordisk Investigational Site	Waco	Texas	United States	76710
255	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84102
256	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84132
257	Novo Nordisk Investigational Site	Bennington	Vermont	United States	05201
258	Novo Nordisk Investigational Site	South Burlington	Vermont	United States	05403
259	Novo Nordisk Investigational Site	Midlothian	Virginia	United States	23114
260	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23510
261	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23249
262	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601-3834
263	Novo Nordisk Investigational Site	Richland	Washington	United States	99352
264	Novo Nordisk Investigational Site	Spokane	Washington	United States	99201
265	Novo Nordisk Investigational Site	Kenosha	Wisconsin	United States	53144
266	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
267	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53295
268	Novo Nordisk Investigational Site	Algiers		Algeria	16000
269	Novo Nordisk Investigational Site	Constantine		Algeria	25000
270	Novo Nordisk Investigational Site	Oran		Algeria	31000
271	Novo Nordisk Investigational Site	Sidi Bel Abbes		Algeria	22000
272	Novo Nordisk Investigational Site	Caba		Argentina	C1440AAD
273	Novo Nordisk Investigational Site	Cordoba		Argentina	5000
274	Novo Nordisk Investigational Site	Mar del Plata		Argentina	B7600FZN
275	Novo Nordisk Investigational Site	Rosario		Argentina	S2000CUD
276	Novo Nordisk Investigational Site	Zarate		Argentina	B2800DGH
277	Novo Nordisk Investigational Site	Fortaleza	Ceara	Brazil	60115-282
278	Novo Nordisk Investigational Site	Brasília	Distrito Federal	Brazil	71625-009
279	Novo Nordisk Investigational Site	Aparecida de Goiania	Goias	Brazil	74935-530
280	Novo Nordisk Investigational Site	Belém	Para	Brazil	66073-000
281	Novo Nordisk Investigational Site	Mogi das Cruzes	Sao Paulo	Brazil	08780-090
282	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01223-001
283	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-000
284	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-200
285	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	05403-000
286	Novo Nordisk Investigational Site	Fortaleza		Brazil	60430-350
287	Novo Nordisk Investigational Site	Porto Alegre		Brazil	90035-170
288	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T5J 3N4
289	Novo Nordisk Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
290	Novo Nordisk Investigational Site	Chatham	Ontario	Canada	N7L 1C1
291	Novo Nordisk Investigational Site	Ottawa	Ontario	Canada	K1K 4L2
292	Novo Nordisk Investigational Site	Sarnia	Ontario	Canada	N7T 4X3
293	Novo Nordisk Investigational Site	Laval	Quebec	Canada	H7T 2P5
294	Novo Nordisk Investigational Site	Bjelovar		Croatia	43000
295	Novo Nordisk Investigational Site	Osijek		Croatia	31 000
296	Novo Nordisk Investigational Site	Slavonski Brod		Croatia	35 000
297	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
298	Novo Nordisk Investigational Site	Zagreb		Croatia	10000
299	Novo Nordisk Investigational Site	Athens		Greece	GR-10552
300	Novo Nordisk Investigational Site	Athens		Greece	GR-115 27
301	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
302	Novo Nordisk Investigational Site	Athens		Greece	GR-17562
303	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54642
304	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57001
305	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500034
306	Novo Nordisk Investigational Site	Hyderbad	Andhra Pradesh	India	500 012
307	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380006
308	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380007
309	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380016
310	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380052
311	Novo Nordisk Investigational Site	Gurgaon	Haryana	India	122001
312	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560 017
313	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560034
314	Novo Nordisk Investigational Site	Kozhikode	Kerala	India	673017
315	Novo Nordisk Investigational Site	Indore	Madhya Pradesh	India	452010
316	Novo Nordisk Investigational Site	Goa	Maharashtra	India	403 202
317	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400007
318	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
319	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400010
320	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
321	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400022
322	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411001
323	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411040
324	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
325	Novo Nordisk Investigational Site	Bhubaneswar	Orissa	India	751005
326	Novo Nordisk Investigational Site	Mohali	Punjab	India	160062
327	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600031
328	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600086
329	Novo Nordisk Investigational Site	Coimbatore	Tamil Nadu	India	641018
330	Novo Nordisk Investigational Site	Lucknow	Uttar Pradesh	India	226014
331	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700020
332	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
333	Novo Nordisk Investigational Site	Ludhiana		India	141001
334	Novo Nordisk Investigational Site	New Delhi		India	110001
335	Novo Nordisk Investigational Site	Bari		Italy	70124
336	Novo Nordisk Investigational Site	Bergamo		Italy	24127
337	Novo Nordisk Investigational Site	Catanzaro		Italy	88100
338	Novo Nordisk Investigational Site	Chieti		Italy	66100
339	Novo Nordisk Investigational Site	Milano (MI)		Italy	20132
340	Novo Nordisk Investigational Site	Milano		Italy	20122
341	Novo Nordisk Investigational Site	Milano		Italy	20162
342	Novo Nordisk Investigational Site	Olbia		Italy	07026
343	Novo Nordisk Investigational Site	Padova		Italy	35143
344	Novo Nordisk Investigational Site	Palermo		Italy	90127
345	Novo Nordisk Investigational Site	Ravenna		Italy	48121
346	Novo Nordisk Investigational Site	Roma		Italy	00133
347	Novo Nordisk Investigational Site	Roma		Italy	00161
348	Novo Nordisk Investigational Site	Sesto San Giovanni (MI)		Italy	20099
349	Novo Nordisk Investigational Site	Chuo-ku, Tokyo		Japan	103-0002
350	Novo Nordisk Investigational Site	Kanagawa		Japan	235-0045
351	Novo Nordisk Investigational Site	Kumamoto		Japan	862-0976
352	Novo Nordisk Investigational Site	Miyazaki		Japan	880-0034
353	Novo Nordisk Investigational Site	Nagano		Japan	390-8621
354	Novo Nordisk Investigational Site	Ota-ku, Tokyo		Japan	1430015
355	Novo Nordisk Investigational Site	Ota-ku		Japan	144 0035
356	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo		Japan	162-8655
357	Novo Nordisk Investigational Site	Goyang		Korea, Republic of	10380
358	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	02841
359	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	03080
360	Novo Nordisk Investigational Site	Suwon-si, Gyeonggi-do		Korea, Republic of	16247
361	Novo Nordisk Investigational Site	Alor Setar		Malaysia	05460
362	Novo Nordisk Investigational Site	Kota Samarahan		Malaysia	94300
363	Novo Nordisk Investigational Site	Kuala Lumpur		Malaysia	59100
364	Novo Nordisk Investigational Site	Kuantan		Malaysia	25100
365	Novo Nordisk Investigational Site	Melaka		Malaysia	75400
366	Novo Nordisk Investigational Site	Serdang		Malaysia	43000
367	Novo Nordisk Investigational Site	Seremban		Malaysia	70300
368	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44130
369	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44150
370	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44600
371	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44650
372	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44670
373	Novo Nordisk Investigational Site	Cuernavaca	Morelos	Mexico	62250
374	Novo Nordisk Investigational Site	Distrito Federal	México, D.F.	Mexico	14080
375	Novo Nordisk Investigational Site	Aguascalientes		Mexico	20230
376	Novo Nordisk Investigational Site	Chihuahua		Mexico	31200
377	Novo Nordisk Investigational Site	San Luis Potosi		Mexico	78200
378	Novo Nordisk Investigational Site	Bytom		Poland	41-902
379	Novo Nordisk Investigational Site	Gdansk		Poland	80-546
380	Novo Nordisk Investigational Site	Krakow		Poland	31-455
381	Novo Nordisk Investigational Site	Oswiecim		Poland	32-600
382	Novo Nordisk Investigational Site	Poznan		Poland	60-589
383	Novo Nordisk Investigational Site	Szczecin		Poland	70-506
384	Novo Nordisk Investigational Site	Warszawa		Poland	02-507
385	Novo Nordisk Investigational Site	Zamosc		Poland	22-400
386	Novo Nordisk Investigational Site	Alba Iulia	Alba	Romania	510053
387	Novo Nordisk Investigational Site	Baia Mare	Maramures	Romania	430222
388	Novo Nordisk Investigational Site	Targu Mures	Mures	Romania	540142
389	Novo Nordisk Investigational Site	Ploiesti	Prahova	Romania	100163
390	Novo Nordisk Investigational Site	Ekaterinburg		Russian Federation	620102
391	Novo Nordisk Investigational Site	Kemerovo		Russian Federation	650002
392	Novo Nordisk Investigational Site	Kirov		Russian Federation	610014
393	Novo Nordisk Investigational Site	Krasnodar		Russian Federation	350012
394	Novo Nordisk Investigational Site	Krasnodar		Russian Federation	350086
395	Novo Nordisk Investigational Site	Moscow		Russian Federation	111539
396	Novo Nordisk Investigational Site	Moscow		Russian Federation	123423
397	Novo Nordisk Investigational Site	Nizhny Novgorod		Russian Federation	603018
398	Novo Nordisk Investigational Site	Rostov-on-Don		Russian Federation	344068
399	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	191119
400	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194356
401	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	195213
402	Novo Nordisk Investigational Site	Saratov		Russian Federation	410031
403	Novo Nordisk Investigational Site	Saratov		Russian Federation	410053
404	Novo Nordisk Investigational Site	St. Petersburg		Russian Federation	194354
405	Novo Nordisk Investigational Site	St. Petersburg		Russian Federation	196084
406	Novo Nordisk Investigational Site	Syktyvkar		Russian Federation	167981
407	Novo Nordisk Investigational Site	Tumen		Russian Federation	625023
408	Novo Nordisk Investigational Site	Tver		Russian Federation	170036
409	Novo Nordisk Investigational Site	Ulianovsk		Russian Federation	432063
410	Novo Nordisk Investigational Site	Volgograd		Russian Federation	400131
411	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150010
412	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6014
413	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6045
414	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1818
415	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2193
416	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2198
417	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0001
418	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4001
419	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4092
420	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal	South Africa	4170
421	Novo Nordisk Investigational Site	Middleburg	Mpumalanga	South Africa	1055
422	Novo Nordisk Investigational Site	Brits	North West	South Africa	0250
423	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7130
424	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7460
425	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7500
426	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7700
427	Novo Nordisk Investigational Site	Granada		Spain	18003
428	Novo Nordisk Investigational Site	Granada		Spain	18012
429	Novo Nordisk Investigational Site	Madrid		Spain	28046
430	Novo Nordisk Investigational Site	Málaga		Spain	29006
431	Novo Nordisk Investigational Site	Sevilla		Spain	41009
432	Novo Nordisk Investigational Site	Valencia		Spain	46014
433	Novo Nordisk Investigational Site	Valencia		Spain	46015
434	Novo Nordisk Investigational Site	Bangkoknoi, Bangkok		Thailand	10700
435	Novo Nordisk Investigational Site	Bangkok		Thailand	10330
436	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
437	Novo Nordisk Investigational Site	Chiang Mai		Thailand	50200
438	Novo Nordisk Investigational Site	Nakhon Ratchasima		Thailand	30000
439	Novo Nordisk Investigational Site	Bristol		United Kingdom	BS10 5NB
440	Novo Nordisk Investigational Site	Dundee		United Kingdom	DD1 9SY
441	Novo Nordisk Investigational Site	Edinburgh		United Kingdom	EH4 2XU
442	Novo Nordisk Investigational Site	Guildford		United Kingdom	GU2 7XX
443	Novo Nordisk Investigational Site	Norwich		United Kingdom	NR4 7TJ
444	Novo Nordisk Investigational Site	Nuneaton		United Kingdom	CV10 7DJ
445	Novo Nordisk Investigational Site	Stevenage		United Kingdom	SG1 4AB
446	Novo Nordisk Investigational Site	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Pollock RF, Heller S, Pieber TR, Woo V, Gundgaard J, Hallén N, Luckevich M, Tutkunkardas D, Zinman B; DEVOTE Study Group. Short-term cost-utility of degludec versus glargine U100 for patients with type 2 diabetes at high risk of hypoglycaemia and cardiovascular events: A Canadian setting (DEVOTE 9). Diabetes Obes Metab. 2019 Jul;21(7):1706-1714. doi: 10.1111/dom.13730. Epub 2019 Apr 14.
• Pollock RF, Valentine WJ, Marso SP, Andersen A, Gundgaard J, Hallén N, Tutkunkardas D, Magnuson EA, Buse JB; DEVOTE study group. Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16). Appl Health Econ Health Policy. 2019 Oct;17(5):615-627. doi: 10.1007/s40258-019-00494-3.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01959529
• Other Study ID Numbers: EX1250-4080; 2013-002371-17; U1111-1141-7614; JapicCTI-142464
• First Posted: Oct 10, 2013
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 438 sites in 20 countries as follows: Algeria: 6; Argentina: 4; Brazil: 10; Canada: 6; Croatia: 5; Greece: 6; India: 26; Italy: 10; Japan: 8; Republic of Korea: 4; Malaysia: 8; Mexico: 7; Poland: 8; Romania: 4; Russian Federation: 20; South Africa: 15; Spain: 6; Thailand: 6; United Kingdom: 8; United States: 271.

Arm/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Subjects received insulin degludec (IDeg) 100 units/mL once daily (OD) subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with insulin aspart (IAsp) at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin twice daily (BID), the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received insulin glargine (IGlar) 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Period Title: Overall Study
STARTED	3818	3819
Exposed	3809	3806
COMPLETED	3742	3747
NOT COMPLETED	76	72

Baseline Characteristics

Arm/Group Title	Insulin Degludec	Insulin Glargine	Total
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.	Total of all reporting groups
Overall Participants	3818	3819	7637
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (7.3)	65.0 (7.5)	65.0 (7.4)
Sex: Female, Male (Count of Participants)
Female	1422 37.2%	1437 37.6%	2859 37.4%
Male	2396 62.8%	2382 62.4%	4778 62.6%
HbA1c (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.44 (1.63)	8.41 (1.67)	8.43 (1.65)

Outcome Measures

1. Primary Outcome

Title	Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke
Description	Time from randomisation to first occurrence of an event adjudication committee (EAC)-confirmed 3-component major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction, or nonfatal stroke. Events with EAC-confirmed onset date between randomisation and individual end of trial were included in the analyses. The number of subjects experiencing first EAC-confirmed MACEs, date between randomisation to the end of trial, both days included were presented. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.
Time Frame	From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)

Outcome Measure Data

Analysis Population Description

The analysis was based on the FAS, which included all randomised subjects.

Arm/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Measure Participants	3818	3819
First EAC-confirmed MACE	325 8.5%	356 9.3%
Myocardial infarction (non-fatal)	143 3.7%	163 4.3%
Stroke (non-fatal)	68 1.8%	74 1.9%
Cardiovascular death	114 3%	119 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec, Insulin Glargine
	Comments	The hazard ratio (HR) (IDeg vs IGlar) was based on Cox regression with investigational medicinal product as only factor for primary analysis.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of IDeg to IGlar was considered confirmed if the upper limit of the two-sided 95% confidence interval for the HR was below 1.3 or equivalent if the p-value for the one-sided test of null hypothesis (H0): HR≥1.3 against the alternative hypothesis (Ha): HR<1.3 was less than 2.5%.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p value : Refers to one-sided test of HR >= 1.3 (against Ha: HR<1.3).
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.908
	Confidence Interval	(2-Sided) 95%; 0.781 to 1.055
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of EAC-confirmed Severe Hypoglycaemic Episodes
Description	Number of severe hypoglycaemic episodes from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.
Time Frame	From randomisation to individual end of trial (maximum patient year observation: 2.75 years)

Outcome Measure Data

Analysis Population Description

The analysis was based on the FAS, which included all randomised subjects.

Arm/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Measure Participants	3818	3819
Number [Number of severe episodes]	280	472

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec, Insulin Glargine
	Comments	Superiority was considered confirmed if the upper limit of the two-sided 95% confidence interval for the rate ratio (RR) was below 1.0 or equivalent if the p-value for the one-sided test of H0: RR ≥1.0 against Ha: RR <1.0, was less than 2.5%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value : Refers to one-sided test of RR >= 1.0 (against Ha: RR<1.0)
	Method	Negative binomial regression
	Comments	The model included treatment (IDeg vs IGlar) as a fixed factor and was fitted using the FAS.
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.601
	Confidence Interval	(2-Sided) 95%; 0.476 to 0.759
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Occurrence of at Least One EAC Confirmed Severe Hypoglycaemic Episode Within a Subject (Yes/no)
Description	Occurrence of at least one EAC-confirmed severe hypoglycaemic episode within a subject from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions.
Time Frame	From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)

Outcome Measure Data

Analysis Population Description

The analysis was based on the FAS, which included all randomised subjects.

Arm/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Measure Participants	3818	3819
Count of Participants [Participants]	187 4.9%	252 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec, Insulin Glargine
	Comments	Superiority of IDeg to IGlar was considered confirmed if the upper limit of the two-sided 95% confidence interval for the odds ratio (OR) was below 1.0 or equivalent if the p-value for the one-sided test of H0: OR ≥1.0 against Ha: OR<1.0, was less than 2.5%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value: Refers to one-sided test of OR >= 1.0 (against Ha: OR<1.0)
	Method	Regression, Logistic
	Comments	The model was logistic regression with log-link function.The model included treatment (IDeg vs IGlar) as a fixed factor and was fitted using the FAS
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.729
	Confidence Interval	(2-Sided) 95%; 0.600 to 0.866
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c)
Description	Mean change in HbA1c from week 0 to month 24.
Time Frame	Randomisation to 24 months

Outcome Measure Data

Analysis Population Description

The analysis was based on the FAS. The number of subjects analysed are the number of subjects with the available data after 24 months.

Arm/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Measure Participants	2431	2404
Mean (Standard Deviation) [percentage of HbA1c]	-0.86 (1.51)	-0.84 (1.57)

Adverse Events

Time Frame	The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months.
Adverse Event Reporting Description	Safety was summarised using the FAS, which included all randomised subjects.
Arm/Group Title	Insulin Degludec		Insulin Glargine
Arm/Group Description	Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.		Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
All Cause Mortality
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1473/3818 (38.6%)		1517/3819 (39.7%)
Blood and lymphatic system disorders
Anaemia	11/3818 (0.3%)	12	34/3819 (0.9%)	40
Autoimmune haemolytic anaemia	0/3818 (0%)	0	1/3819 (0%)	1
Coagulopathy	1/3818 (0%)	1	1/3819 (0%)	1
Coombs negative haemolytic anaemia	0/3818 (0%)	0	1/3819 (0%)	1
Evans syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Haemolytic anaemia	0/3818 (0%)	0	1/3819 (0%)	2
Haemorrhagic anaemia	7/3818 (0.2%)	7	9/3819 (0.2%)	9
Hypochromic anaemia	0/3818 (0%)	0	1/3819 (0%)	1
Iron deficiency anaemia	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Leukocytosis	3/3818 (0.1%)	4	2/3819 (0.1%)	2
Nephrogenic anaemia	1/3818 (0%)	1	0/3819 (0%)	0
Neutropenia	1/3818 (0%)	1	3/3819 (0.1%)	3
Normochromic normocytic anaemia	1/3818 (0%)	1	2/3819 (0.1%)	2
Pancytopenia	0/3818 (0%)	0	1/3819 (0%)	1
Thrombocytopenia	1/3818 (0%)	1	0/3819 (0%)	0
Cardiac disorders
Acute coronary syndrome	11/3818 (0.3%)	12	8/3819 (0.2%)	8
Acute left ventricular failure	7/3818 (0.2%)	7	6/3819 (0.2%)	6
Acute myocardial infarction	98/3818 (2.6%)	111	115/3819 (3%)	123
Angina pectoris	36/3818 (0.9%)	37	48/3819 (1.3%)	53
Angina unstable	87/3818 (2.3%)	94	79/3819 (2.1%)	93
Aortic valve disease	3/3818 (0.1%)	3	0/3819 (0%)	0
Aortic valve stenosis	7/3818 (0.2%)	8	5/3819 (0.1%)	5
Arrhythmia	1/3818 (0%)	1	5/3819 (0.1%)	5
Arteriosclerosis coronary artery	4/3818 (0.1%)	4	7/3819 (0.2%)	7
Arteriospasm coronary	1/3818 (0%)	1	0/3819 (0%)	0
Atrial fibrillation	47/3818 (1.2%)	55	56/3819 (1.5%)	75
Atrial flutter	11/3818 (0.3%)	11	6/3819 (0.2%)	6
Atrial tachycardia	1/3818 (0%)	1	3/3819 (0.1%)	3
Atrioventricular block	0/3818 (0%)	0	3/3819 (0.1%)	3
Atrioventricular block complete	6/3818 (0.2%)	6	3/3819 (0.1%)	3
Atrioventricular block first degree	2/3818 (0.1%)	2	0/3819 (0%)	0
Atrioventricular block second degree	2/3818 (0.1%)	2	1/3819 (0%)	1
Atrioventricular dissociation	0/3818 (0%)	0	2/3819 (0.1%)	2
Bradycardia	8/3818 (0.2%)	9	9/3819 (0.2%)	9
Bundle branch block left	2/3818 (0.1%)	2	0/3819 (0%)	0
Bundle branch block right	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac arrest	26/3818 (0.7%)	26	20/3819 (0.5%)	21
Cardiac discomfort	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac disorder	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac failure	24/3818 (0.6%)	26	30/3819 (0.8%)	33
Cardiac failure acute	7/3818 (0.2%)	7	8/3819 (0.2%)	8
Cardiac failure chronic	8/3818 (0.2%)	12	10/3819 (0.3%)	11
Cardiac failure congestive	134/3818 (3.5%)	177	143/3819 (3.7%)	206
Cardiac hypertrophy	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac ventricular thrombosis	1/3818 (0%)	1	1/3819 (0%)	1
Cardio-respiratory arrest	12/3818 (0.3%)	12	9/3819 (0.2%)	9
Cardiogenic shock	1/3818 (0%)	1	1/3819 (0%)	1
Cardiomegaly	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Cardiomyopathy	4/3818 (0.1%)	4	7/3819 (0.2%)	7
Cardiopulmonary failure	1/3818 (0%)	1	2/3819 (0.1%)	2
Cardiorenal syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Cardiovascular disorder	0/3818 (0%)	0	1/3819 (0%)	1
Chordae tendinae rupture	0/3818 (0%)	0	1/3819 (0%)	1
Chronic left ventricular failure	0/3818 (0%)	0	1/3819 (0%)	1
Congestive cardiomyopathy	3/3818 (0.1%)	3	0/3819 (0%)	0
Cor pulmonale	1/3818 (0%)	1	2/3819 (0.1%)	2
Cor pulmonale acute	1/3818 (0%)	1	0/3819 (0%)	0
Coronary artery disease	80/3818 (2.1%)	85	89/3819 (2.3%)	91
Coronary artery dissection	1/3818 (0%)	1	0/3819 (0%)	0
Coronary artery embolism	0/3818 (0%)	0	1/3819 (0%)	1
Coronary artery insufficiency	1/3818 (0%)	1	1/3819 (0%)	1
Coronary artery occlusion	12/3818 (0.3%)	12	5/3819 (0.1%)	6
Coronary artery stenosis	12/3818 (0.3%)	12	5/3819 (0.1%)	5
Coronary ostial stenosis	1/3818 (0%)	1	0/3819 (0%)	0
Diastolic dysfunction	1/3818 (0%)	1	0/3819 (0%)	0
Heart valve incompetence	0/3818 (0%)	0	1/3819 (0%)	1
Hypertensive cardiomyopathy	0/3818 (0%)	0	1/3819 (0%)	1
Hypertensive heart disease	1/3818 (0%)	1	4/3819 (0.1%)	4
Intracardiac thrombus	1/3818 (0%)	1	0/3819 (0%)	0
Ischaemic cardiomyopathy	3/3818 (0.1%)	3	7/3819 (0.2%)	7
Left ventricular dysfunction	1/3818 (0%)	1	3/3819 (0.1%)	3
Left ventricular failure	6/3818 (0.2%)	7	3/3819 (0.1%)	3
Left ventricular hypertrophy	1/3818 (0%)	1	0/3819 (0%)	0
Long QT syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Mitral valve incompetence	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Myocardial infarction	48/3818 (1.3%)	51	66/3819 (1.7%)	68
Myocardial ischaemia	7/3818 (0.2%)	7	9/3819 (0.2%)	9
Nodal arrhythmia	1/3818 (0%)	1	1/3819 (0%)	1
Palpitations	1/3818 (0%)	1	1/3819 (0%)	1
Pericardial effusion	1/3818 (0%)	1	2/3819 (0.1%)	2
Pericarditis	1/3818 (0%)	1	1/3819 (0%)	1
Prinzmetal angina	0/3818 (0%)	0	1/3819 (0%)	1
Pulseless electrical activity	1/3818 (0%)	1	0/3819 (0%)	0
Restrictive cardiomyopathy	0/3818 (0%)	0	1/3819 (0%)	1
Right ventricular failure	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Silent myocardial infarction	4/3818 (0.1%)	4	2/3819 (0.1%)	2
Sinus arrest	0/3818 (0%)	0	1/3819 (0%)	1
Sinus bradycardia	1/3818 (0%)	1	3/3819 (0.1%)	3
Sinus node dysfunction	6/3818 (0.2%)	6	5/3819 (0.1%)	5
Sinus tachycardia	1/3818 (0%)	1	0/3819 (0%)	0
Stress cardiomyopathy	1/3818 (0%)	1	0/3819 (0%)	0
Supraventricular tachycardia	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Systolic dysfunction	1/3818 (0%)	1	0/3819 (0%)	0
Tachyarrhythmia	0/3818 (0%)	0	1/3819 (0%)	1
Tachycardia	1/3818 (0%)	1	5/3819 (0.1%)	5
Tricuspid valve incompetence	1/3818 (0%)	1	1/3819 (0%)	1
Trifascicular block	0/3818 (0%)	0	2/3819 (0.1%)	2
Ventricular arrhythmia	1/3818 (0%)	1	0/3819 (0%)	0
Ventricular extrasystoles	0/3818 (0%)	0	2/3819 (0.1%)	2
Ventricular fibrillation	6/3818 (0.2%)	7	5/3819 (0.1%)	5
Ventricular hypokinesia	1/3818 (0%)	1	1/3819 (0%)	1
Ventricular tachycardia	8/3818 (0.2%)	9	12/3819 (0.3%)	16
Congenital, familial and genetic disorders
Congenital ureterocele	1/3818 (0%)	1	0/3819 (0%)	0
Factor V deficiency	0/3818 (0%)	0	1/3819 (0%)	1
Gastrointestinal arteriovenous malformation	0/3818 (0%)	0	1/3819 (0%)	1
Haemorrhagic arteriovenous malformation	0/3818 (0%)	0	2/3819 (0.1%)	2
Hypertrophic cardiomyopathy	0/3818 (0%)	0	1/3819 (0%)	1
Osteogenesis imperfecta	0/3818 (0%)	0	1/3819 (0%)	1
Phimosis	0/3818 (0%)	0	2/3819 (0.1%)	2
Ear and labyrinth disorders
Deafness neurosensory	1/3818 (0%)	1	0/3819 (0%)	0
Inner ear disorder	0/3818 (0%)	0	1/3819 (0%)	1
Meniere's disease	1/3818 (0%)	1	0/3819 (0%)	0
Sudden hearing loss	1/3818 (0%)	1	0/3819 (0%)	0
Vertigo	5/3818 (0.1%)	5	3/3819 (0.1%)	3
Vertigo positional	1/3818 (0%)	1	3/3819 (0.1%)	3
Vestibular disorder	0/3818 (0%)	0	1/3819 (0%)	1
Endocrine disorders
Adrenal insufficiency	1/3818 (0%)	1	0/3819 (0%)	0
Goitre	1/3818 (0%)	1	1/3819 (0%)	1
Hypothyroidism	2/3818 (0.1%)	2	0/3819 (0%)	0
Thyroid mass	2/3818 (0.1%)	2	0/3819 (0%)	0
Toxic goitre	0/3818 (0%)	0	1/3819 (0%)	1
Toxic nodular goitre	0/3818 (0%)	0	1/3819 (0%)	1
Eye disorders
Blindness	0/3818 (0%)	0	2/3819 (0.1%)	2
Cataract	9/3818 (0.2%)	13	3/3819 (0.1%)	4
Cataract diabetic	1/3818 (0%)	1	0/3819 (0%)	0
Diabetic retinopathy	4/3818 (0.1%)	4	1/3819 (0%)	1
Glaucoma	1/3818 (0%)	1	1/3819 (0%)	1
Macular fibrosis	1/3818 (0%)	1	2/3819 (0.1%)	2
Neurotrophic keratopathy	0/3818 (0%)	0	1/3819 (0%)	1
Optic ischaemic neuropathy	1/3818 (0%)	1	0/3819 (0%)	0
Pterygium	0/3818 (0%)	0	1/3819 (0%)	1
Retinal artery occlusion	1/3818 (0%)	1	0/3819 (0%)	0
Retinal detachment	1/3818 (0%)	1	1/3819 (0%)	1
Retinal vein occlusion	1/3818 (0%)	1	0/3819 (0%)	0
Retinopathy	0/3818 (0%)	0	1/3819 (0%)	1
Retinopathy proliferative	1/3818 (0%)	1	0/3819 (0%)	0
Visual impairment	0/3818 (0%)	0	1/3819 (0%)	1
Vitreous haemorrhage	0/3818 (0%)	0	2/3819 (0.1%)	2
Gastrointestinal disorders
Abdominal discomfort	0/3818 (0%)	0	1/3819 (0%)	1
Abdominal hernia	1/3818 (0%)	1	1/3819 (0%)	1
Abdominal hernia obstructive	0/3818 (0%)	0	2/3819 (0.1%)	2
Abdominal mass	1/3818 (0%)	1	0/3819 (0%)	0
Abdominal pain	10/3818 (0.3%)	10	10/3819 (0.3%)	10
Abdominal pain upper	3/3818 (0.1%)	3	1/3819 (0%)	1
Abdominal wall haematoma	1/3818 (0%)	1	0/3819 (0%)	0
Acid peptic disease	0/3818 (0%)	0	1/3819 (0%)	1
Acute abdomen	0/3818 (0%)	0	1/3819 (0%)	1
Alcoholic pancreatitis	1/3818 (0%)	1	0/3819 (0%)	0
Appendix disorder	0/3818 (0%)	0	1/3819 (0%)	1
Ascites	0/3818 (0%)	0	1/3819 (0%)	1
Barrett's oesophagus	1/3818 (0%)	1	1/3819 (0%)	1
Chronic gastritis	1/3818 (0%)	1	2/3819 (0.1%)	2
Colitis	6/3818 (0.2%)	6	6/3819 (0.2%)	6
Colitis ischaemic	3/3818 (0.1%)	6	2/3819 (0.1%)	2
Constipation	4/3818 (0.1%)	4	0/3819 (0%)	0
Crohn's disease	1/3818 (0%)	1	2/3819 (0.1%)	2
Diabetic gastroparesis	1/3818 (0%)	1	2/3819 (0.1%)	2
Diarrhoea	11/3818 (0.3%)	14	3/3819 (0.1%)	3
Diverticular perforation	1/3818 (0%)	1	0/3819 (0%)	0
Diverticulum	5/3818 (0.1%)	5	0/3819 (0%)	0
Diverticulum intestinal	2/3818 (0.1%)	2	0/3819 (0%)	0
Diverticulum intestinal haemorrhagic	0/3818 (0%)	0	1/3819 (0%)	1
Duodenal stenosis	0/3818 (0%)	0	1/3819 (0%)	1
Duodenal ulcer	1/3818 (0%)	1	1/3819 (0%)	1
Duodenal ulcer haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Duodenal vascular ectasia	1/3818 (0%)	1	0/3819 (0%)	0
Duodenitis	1/3818 (0%)	1	0/3819 (0%)	0
Dysphagia	0/3818 (0%)	0	3/3819 (0.1%)	3
Enteritis	1/3818 (0%)	1	0/3819 (0%)	0
Enterocele	1/3818 (0%)	1	0/3819 (0%)	0
Epigastric discomfort	1/3818 (0%)	1	0/3819 (0%)	0
Erosive duodenitis	0/3818 (0%)	0	1/3819 (0%)	1
Gastric antral vascular ectasia	0/3818 (0%)	0	1/3819 (0%)	1
Gastric perforation	1/3818 (0%)	1	1/3819 (0%)	1
Gastric ulcer	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Gastric ulcer haemorrhage	1/3818 (0%)	2	0/3819 (0%)	0
Gastric ulcer perforation	0/3818 (0%)	0	1/3819 (0%)	2
Gastritis	8/3818 (0.2%)	8	6/3819 (0.2%)	7
Gastritis erosive	2/3818 (0.1%)	2	0/3819 (0%)	0
Gastroduodenitis haemorrhagic	1/3818 (0%)	1	0/3819 (0%)	0
Gastrointestinal angiodysplasia	1/3818 (0%)	1	0/3819 (0%)	0
Gastrointestinal haemorrhage	10/3818 (0.3%)	10	15/3819 (0.4%)	16
Gastrointestinal polyp haemorrhage	1/3818 (0%)	1	1/3819 (0%)	1
Gastrointestinal ulcer haemorrhage	0/3818 (0%)	0	2/3819 (0.1%)	2
Gastrooesophageal reflux disease	6/3818 (0.2%)	7	9/3819 (0.2%)	10
Haematochezia	1/3818 (0%)	2	4/3819 (0.1%)	4
Haemorrhoidal haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Haemorrhoids	4/3818 (0.1%)	4	1/3819 (0%)	1
Hiatus hernia	0/3818 (0%)	0	2/3819 (0.1%)	2
Ileus	2/3818 (0.1%)	2	0/3819 (0%)	0
Ileus paralytic	0/3818 (0%)	0	1/3819 (0%)	1
Impaired gastric emptying	4/3818 (0.1%)	5	7/3819 (0.2%)	9
Inguinal hernia	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Intestinal ischaemia	2/3818 (0.1%)	2	1/3819 (0%)	1
Intestinal obstruction	4/3818 (0.1%)	4	2/3819 (0.1%)	2
Intestinal perforation	0/3818 (0%)	0	2/3819 (0.1%)	2
Intra-abdominal haematoma	1/3818 (0%)	1	0/3819 (0%)	0
Irritable bowel syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Large intestinal haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Large intestinal ulcer haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Large intestine polyp	4/3818 (0.1%)	4	3/3819 (0.1%)	3
Lower gastrointestinal haemorrhage	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Mallory-Weiss syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Mesenteric haematoma	1/3818 (0%)	1	0/3819 (0%)	0
Nausea	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Neutropenic colitis	0/3818 (0%)	0	1/3819 (0%)	1
Oesophageal rupture	0/3818 (0%)	0	1/3819 (0%)	1
Oesophageal ulcer haemorrhage	1/3818 (0%)	1	1/3819 (0%)	1
Oesophageal varices haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Oesophagitis	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Pancreatic mass	1/3818 (0%)	1	0/3819 (0%)	0
Pancreatitis	7/3818 (0.2%)	8	5/3819 (0.1%)	5
Pancreatitis acute	6/3818 (0.2%)	7	11/3819 (0.3%)	16
Pancreatitis chronic	1/3818 (0%)	1	2/3819 (0.1%)	2
Peptic ulcer	2/3818 (0.1%)	2	1/3819 (0%)	2
Peptic ulcer perforation	1/3818 (0%)	1	0/3819 (0%)	0
Periodontal disease	1/3818 (0%)	1	0/3819 (0%)	0
Pneumatosis intestinalis	0/3818 (0%)	0	1/3819 (0%)	1
Rectal haemorrhage	1/3818 (0%)	1	3/3819 (0.1%)	3
Rectal ulcer haemorrhage	1/3818 (0%)	1	0/3819 (0%)	0
Salivary gland calculus	1/3818 (0%)	1	0/3819 (0%)	0
Salivary gland mass	1/3818 (0%)	1	0/3819 (0%)	0
Small intestinal obstruction	9/3818 (0.2%)	10	6/3819 (0.2%)	6
Spigelian hernia	1/3818 (0%)	1	0/3819 (0%)	0
Umbilical hernia	1/3818 (0%)	1	2/3819 (0.1%)	2
Upper gastrointestinal haemorrhage	0/3818 (0%)	0	8/3819 (0.2%)	8
Varices oesophageal	0/3818 (0%)	0	1/3819 (0%)	1
Vomiting	5/3818 (0.1%)	5	7/3819 (0.2%)	7
General disorders
Asthenia	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Cardiac complication associated with device	1/3818 (0%)	1	0/3819 (0%)	0
Cardiac death	1/3818 (0%)	1	2/3819 (0.1%)	2
Catheter site haematoma	0/3818 (0%)	0	1/3819 (0%)	1
Chest discomfort	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Chest pain	16/3818 (0.4%)	16	21/3819 (0.5%)	22
Complication associated with device	1/3818 (0%)	1	0/3819 (0%)	0
Cyst	1/3818 (0%)	1	1/3819 (0%)	1
Death	27/3818 (0.7%)	27	21/3819 (0.5%)	21
Fatigue	1/3818 (0%)	1	1/3819 (0%)	1
Foreign body reaction	1/3818 (0%)	1	0/3819 (0%)	0
Gait disturbance	1/3818 (0%)	1	1/3819 (0%)	1
Generalised oedema	4/3818 (0.1%)	4	3/3819 (0.1%)	3
Impaired healing	1/3818 (0%)	1	2/3819 (0.1%)	2
Local swelling	1/3818 (0%)	1	0/3819 (0%)	0
Medical device site haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Multiple organ dysfunction syndrome	1/3818 (0%)	1	2/3819 (0.1%)	2
Non-cardiac chest pain	47/3818 (1.2%)	48	54/3819 (1.4%)	63
Oedema	0/3818 (0%)	0	3/3819 (0.1%)	4
Oedema due to cardiac disease	1/3818 (0%)	1	0/3819 (0%)	0
Oedema peripheral	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Pain	2/3818 (0.1%)	2	0/3819 (0%)	0
Peripheral swelling	1/3818 (0%)	1	2/3819 (0.1%)	2
Polyp	1/3818 (0%)	1	0/3819 (0%)	0
Pyrexia	1/3818 (0%)	1	1/3819 (0%)	1
Sudden cardiac death	1/3818 (0%)	1	3/3819 (0.1%)	3
Sudden death	1/3818 (0%)	1	8/3819 (0.2%)	8
Surgical failure	1/3818 (0%)	1	0/3819 (0%)	0
Systemic inflammatory response syndrome	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Vascular stent restenosis	3/3818 (0.1%)	3	2/3819 (0.1%)	3
Vascular stent stenosis	1/3818 (0%)	1	0/3819 (0%)	0
Vascular stent thrombosis	1/3818 (0%)	1	0/3819 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	1/3818 (0%)	1	1/3819 (0%)	1
Alcoholic liver disease	1/3818 (0%)	1	0/3819 (0%)	0
Bile duct obstruction	0/3818 (0%)	0	2/3819 (0.1%)	2
Bile duct stone	1/3818 (0%)	1	1/3819 (0%)	1
Biliary dyskinesia	0/3818 (0%)	0	1/3819 (0%)	1
Cholangitis	1/3818 (0%)	1	2/3819 (0.1%)	2
Cholecystitis	8/3818 (0.2%)	8	4/3819 (0.1%)	4
Cholecystitis acute	6/3818 (0.2%)	6	4/3819 (0.1%)	4
Cholecystitis chronic	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Cholelithiasis	8/3818 (0.2%)	8	8/3819 (0.2%)	8
Chronic hepatic failure	0/3818 (0%)	0	1/3819 (0%)	1
Dilatation intrahepatic duct acquired	0/3818 (0%)	0	1/3819 (0%)	1
Hepatic cirrhosis	3/3818 (0.1%)	3	1/3819 (0%)	1
Hepatic failure	1/3818 (0%)	1	0/3819 (0%)	0
Hepatic lesion	0/3818 (0%)	0	1/3819 (0%)	1
Hepatitis chronic active	1/3818 (0%)	1	0/3819 (0%)	0
Hepatorenal failure	0/3818 (0%)	0	1/3819 (0%)	1
Hepatorenal syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Ischaemic hepatitis	0/3818 (0%)	0	1/3819 (0%)	1
Jaundice	0/3818 (0%)	0	1/3819 (0%)	1
Jaundice cholestatic	1/3818 (0%)	1	0/3819 (0%)	0
Liver disorder	1/3818 (0%)	1	1/3819 (0%)	1
Non-alcoholic steatohepatitis	0/3818 (0%)	0	1/3819 (0%)	1
Portal vein thrombosis	1/3818 (0%)	1	0/3819 (0%)	0
Sphincter of Oddi dysfunction	1/3818 (0%)	1	0/3819 (0%)	0
Steatohepatitis	1/3818 (0%)	1	0/3819 (0%)	0
Immune system disorders
Anaphylactic reaction	0/3818 (0%)	0	1/3819 (0%)	1
Anaphylactic shock	1/3818 (0%)	1	0/3819 (0%)	0
Drug hypersensitivity	1/3818 (0%)	1	2/3819 (0.1%)	2
Renal transplant failure	1/3818 (0%)	1	0/3819 (0%)	0
Infections and infestations
Abdominal abscess	0/3818 (0%)	0	1/3819 (0%)	1
Abdominal sepsis	1/3818 (0%)	1	0/3819 (0%)	0
Abdominal wall abscess	2/3818 (0.1%)	2	1/3819 (0%)	1
Abdominal wall infection	1/3818 (0%)	1	0/3819 (0%)	0
Abscess limb	0/3818 (0%)	0	5/3819 (0.1%)	5
Abscess rupture	0/3818 (0%)	0	1/3819 (0%)	1
Abscess soft tissue	0/3818 (0%)	0	1/3819 (0%)	1
Acute endocarditis	1/3818 (0%)	1	0/3819 (0%)	0
Appendicitis	4/3818 (0.1%)	4	6/3819 (0.2%)	6
Arteriosclerotic gangrene	0/3818 (0%)	0	1/3819 (0%)	1
Arthritis bacterial	4/3818 (0.1%)	4	3/3819 (0.1%)	3
Bacteraemia	0/3818 (0%)	0	1/3819 (0%)	1
Bacterial infection	1/3818 (0%)	1	0/3819 (0%)	0
Bacterial pyelonephritis	1/3818 (0%)	1	0/3819 (0%)	0
Bacterial sepsis	0/3818 (0%)	0	1/3819 (0%)	1
Beta haemolytic streptococcal infection	1/3818 (0%)	1	2/3819 (0.1%)	2
Bronchitis	16/3818 (0.4%)	17	21/3819 (0.5%)	21
Bronchitis bacterial	1/3818 (0%)	1	1/3819 (0%)	1
Bronchitis viral	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Catheter site infection	1/3818 (0%)	1	0/3819 (0%)	0
Cellulitis	52/3818 (1.4%)	64	61/3819 (1.6%)	72
Cellulitis orbital	0/3818 (0%)	0	1/3819 (0%)	1
Cellulitis staphylococcal	1/3818 (0%)	1	2/3819 (0.1%)	2
Cellulitis streptococcal	1/3818 (0%)	1	0/3819 (0%)	0
Chest wall abscess	1/3818 (0%)	1	0/3819 (0%)	0
Cholecystitis infective	1/3818 (0%)	1	1/3819 (0%)	1
Clostridium difficile colitis	8/3818 (0.2%)	8	4/3819 (0.1%)	4
Clostridium difficile infection	0/3818 (0%)	0	1/3819 (0%)	1
Colonic abscess	0/3818 (0%)	0	1/3819 (0%)	1
Conjunctivitis	1/3818 (0%)	1	0/3819 (0%)	0
Cystitis	1/3818 (0%)	1	3/3819 (0.1%)	3
Dengue fever	3/3818 (0.1%)	3	0/3819 (0%)	0
Dermatitis infected	1/3818 (0%)	1	0/3819 (0%)	0
Device related infection	3/3818 (0.1%)	3	1/3819 (0%)	1
Diabetic foot infection	4/3818 (0.1%)	4	8/3819 (0.2%)	8
Diabetic gangrene	0/3818 (0%)	0	2/3819 (0.1%)	2
Disseminated cryptococcosis	1/3818 (0%)	1	0/3819 (0%)	0
Diverticulitis	11/3818 (0.3%)	13	14/3819 (0.4%)	14
Dysentery	1/3818 (0%)	1	0/3819 (0%)	0
Eczema infected	0/3818 (0%)	0	2/3819 (0.1%)	2
Empyema	1/3818 (0%)	1	0/3819 (0%)	0
Endocarditis	0/3818 (0%)	0	1/3819 (0%)	1
Epiglottitis	1/3818 (0%)	1	0/3819 (0%)	0
Erysipelas	0/3818 (0%)	0	1/3819 (0%)	1
Escherichia sepsis	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Escherichia urinary tract infection	1/3818 (0%)	1	0/3819 (0%)	0
External ear cellulitis	1/3818 (0%)	1	0/3819 (0%)	0
Extradural abscess	0/3818 (0%)	0	2/3819 (0.1%)	2
Gangrene	5/3818 (0.1%)	5	13/3819 (0.3%)	16
Gas gangrene	1/3818 (0%)	2	0/3819 (0%)	0
Gastroenteritis	13/3818 (0.3%)	13	12/3819 (0.3%)	12
Gastroenteritis Escherichia coli	0/3818 (0%)	0	1/3819 (0%)	1
Gastroenteritis viral	2/3818 (0.1%)	2	7/3819 (0.2%)	7
Graft infection	0/3818 (0%)	0	1/3819 (0%)	1
Groin abscess	1/3818 (0%)	1	0/3819 (0%)	0
H1N1 influenza	0/3818 (0%)	0	1/3819 (0%)	1
Helicobacter gastritis	1/3818 (0%)	1	0/3819 (0%)	0
Herpes zoster	3/3818 (0.1%)	3	0/3819 (0%)	0
Incision site infection	1/3818 (0%)	1	1/3819 (0%)	1
Infected bite	0/3818 (0%)	0	1/3819 (0%)	1
Infected dermal cyst	1/3818 (0%)	1	0/3819 (0%)	0
Infected seroma	0/3818 (0%)	0	1/3819 (0%)	1
Infected skin ulcer	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Infectious colitis	0/3818 (0%)	0	2/3819 (0.1%)	2
Influenza	5/3818 (0.1%)	5	3/3819 (0.1%)	3
Infusion site infection	0/3818 (0%)	0	1/3819 (0%)	2
Intervertebral discitis	0/3818 (0%)	0	1/3819 (0%)	1
Joint abscess	1/3818 (0%)	1	0/3819 (0%)	0
Klebsiella sepsis	0/3818 (0%)	0	1/3819 (0%)	1
Labyrinthitis	2/3818 (0.1%)	2	0/3819 (0%)	0
Liver abscess	0/3818 (0%)	0	1/3819 (0%)	1
Localised infection	4/3818 (0.1%)	4	3/3819 (0.1%)	3
Lower respiratory tract infection	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Lyme disease	0/3818 (0%)	0	1/3819 (0%)	1
Meningitis aseptic	1/3818 (0%)	1	0/3819 (0%)	0
Meningitis viral	1/3818 (0%)	1	0/3819 (0%)	0
Mucormycosis	1/3818 (0%)	1	0/3819 (0%)	0
Necrotising fasciitis	1/3818 (0%)	1	0/3819 (0%)	0
Oesophageal candidiasis	0/3818 (0%)	0	3/3819 (0.1%)	3
Oral candidiasis	0/3818 (0%)	0	1/3819 (0%)	1
Orchitis	0/3818 (0%)	0	2/3819 (0.1%)	2
Osteomyelitis	20/3818 (0.5%)	26	22/3819 (0.6%)	23
Osteomyelitis acute	1/3818 (0%)	1	1/3819 (0%)	1
Osteomyelitis chronic	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Otitis externa	1/3818 (0%)	1	1/3819 (0%)	2
Otitis media chronic	1/3818 (0%)	1	0/3819 (0%)	0
Paraspinal abscess	1/3818 (0%)	1	0/3819 (0%)	0
Paronychia	1/3818 (0%)	1	1/3819 (0%)	1
Perineal abscess	1/3818 (0%)	1	0/3819 (0%)	0
Perirectal abscess	0/3818 (0%)	0	2/3819 (0.1%)	2
Peritoneal abscess	0/3818 (0%)	0	1/3819 (0%)	1
Peritonitis	2/3818 (0.1%)	2	0/3819 (0%)	0
Peritonitis bacterial	0/3818 (0%)	0	1/3819 (0%)	1
Pharyngitis	0/3818 (0%)	0	1/3819 (0%)	1
Pilonidal cyst	0/3818 (0%)	0	1/3819 (0%)	1
Pneumonia	90/3818 (2.4%)	99	90/3819 (2.4%)	102
Pneumonia bacterial	2/3818 (0.1%)	2	4/3819 (0.1%)	4
Pneumonia influenzal	0/3818 (0%)	0	2/3819 (0.1%)	2
Pneumonia klebsiella	0/3818 (0%)	0	2/3819 (0.1%)	2
Pneumonia mycoplasmal	1/3818 (0%)	1	0/3819 (0%)	0
Pneumonia pneumococcal	0/3818 (0%)	0	1/3819 (0%)	1
Pneumonia pseudomonal	1/3818 (0%)	1	2/3819 (0.1%)	2
Pneumonia staphylococcal	1/3818 (0%)	1	2/3819 (0.1%)	2
Pneumonia streptococcal	2/3818 (0.1%)	2	0/3819 (0%)	0
Pneumonia viral	0/3818 (0%)	0	1/3819 (0%)	1
Post procedural cellulitis	1/3818 (0%)	1	0/3819 (0%)	0
Post procedural infection	8/3818 (0.2%)	8	2/3819 (0.1%)	2
Post procedural sepsis	0/3818 (0%)	0	1/3819 (0%)	1
Postoperative abscess	3/3818 (0.1%)	3	0/3819 (0%)	0
Postoperative wound infection	11/3818 (0.3%)	12	2/3819 (0.1%)	2
Prostate infection	0/3818 (0%)	0	1/3819 (0%)	1
Prostatitis Escherichia coli	0/3818 (0%)	0	1/3819 (0%)	1
Pseudomonal bacteraemia	0/3818 (0%)	0	1/3819 (0%)	1
Pulmonary sepsis	2/3818 (0.1%)	2	4/3819 (0.1%)	4
Pyelonephritis	2/3818 (0.1%)	2	11/3819 (0.3%)	11
Pyelonephritis acute	4/3818 (0.1%)	4	1/3819 (0%)	1
Pyuria	0/3818 (0%)	0	1/3819 (0%)	1
Rectal abscess	1/3818 (0%)	1	1/3819 (0%)	1
Renal abscess	0/3818 (0%)	0	1/3819 (0%)	1
Respiratory syncytial virus bronchitis	0/3818 (0%)	0	1/3819 (0%)	1
Respiratory tract infection	2/3818 (0.1%)	2	1/3819 (0%)	1
Respiratory tract infection viral	0/3818 (0%)	0	1/3819 (0%)	1
Salpingitis	1/3818 (0%)	1	0/3819 (0%)	0
Sepsis	36/3818 (0.9%)	37	31/3819 (0.8%)	31
Sepsis pasteurella	1/3818 (0%)	1	0/3819 (0%)	0
Sepsis syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Septic arthritis staphylococcal	1/3818 (0%)	1	1/3819 (0%)	1
Septic embolus	0/3818 (0%)	0	1/3819 (0%)	1
Septic shock	11/3818 (0.3%)	11	12/3819 (0.3%)	13
Sialoadenitis	1/3818 (0%)	1	0/3819 (0%)	0
Sinusitis	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Soft tissue infection	2/3818 (0.1%)	2	0/3819 (0%)	0
Staphylococcal abscess	0/3818 (0%)	0	2/3819 (0.1%)	2
Staphylococcal bacteraemia	0/3818 (0%)	0	2/3819 (0.1%)	2
Staphylococcal infection	3/3818 (0.1%)	3	5/3819 (0.1%)	6
Staphylococcal sepsis	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Streptococcal bacteraemia	0/3818 (0%)	0	3/3819 (0.1%)	3
Streptococcal sepsis	3/3818 (0.1%)	3	0/3819 (0%)	0
Subcutaneous abscess	1/3818 (0%)	1	3/3819 (0.1%)	3
Subdiaphragmatic abscess	1/3818 (0%)	1	0/3819 (0%)	0
Tooth abscess	0/3818 (0%)	0	1/3819 (0%)	1
Tracheobronchitis	0/3818 (0%)	0	2/3819 (0.1%)	2
Tuberculosis	0/3818 (0%)	0	1/3819 (0%)	1
Upper respiratory tract infection	5/3818 (0.1%)	5	5/3819 (0.1%)	5
Urinary tract infection	34/3818 (0.9%)	37	30/3819 (0.8%)	37
Urinary tract infection bacterial	0/3818 (0%)	0	2/3819 (0.1%)	3
Urosepsis	10/3818 (0.3%)	11	9/3819 (0.2%)	9
Viraemia	1/3818 (0%)	1	0/3819 (0%)	0
Viral infection	1/3818 (0%)	1	3/3819 (0.1%)	3
Viral pericarditis	1/3818 (0%)	1	0/3819 (0%)	0
Vulval abscess	1/3818 (0%)	1	1/3819 (0%)	1
Wound infection	2/3818 (0.1%)	2	4/3819 (0.1%)	4
Injury, poisoning and procedural complications
Accident at work	0/3818 (0%)	0	2/3819 (0.1%)	2
Accidental overdose	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Alcohol poisoning	2/3818 (0.1%)	2	0/3819 (0%)	0
Anaemia postoperative	1/3818 (0%)	1	0/3819 (0%)	0
Anaesthetic complication	1/3818 (0%)	1	0/3819 (0%)	0
Anaesthetic complication pulmonary	0/3818 (0%)	0	1/3819 (0%)	1
Anastomotic ulcer	0/3818 (0%)	0	1/3819 (0%)	1
Animal bite	0/3818 (0%)	0	1/3819 (0%)	1
Ankle fracture	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Brachial plexus injury	0/3818 (0%)	0	1/3819 (0%)	1
Burns third degree	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac valve replacement complication	1/3818 (0%)	1	0/3819 (0%)	0
Cervical vertebral fracture	0/3818 (0%)	0	1/3819 (0%)	1
Clavicle fracture	1/3818 (0%)	1	0/3819 (0%)	0
Concussion	1/3818 (0%)	1	0/3819 (0%)	0
Contusion	1/3818 (0%)	2	0/3819 (0%)	0
Coronary artery restenosis	2/3818 (0.1%)	2	1/3819 (0%)	1
Coronary vascular graft occlusion	2/3818 (0.1%)	2	1/3819 (0%)	1
Craniocerebral injury	1/3818 (0%)	1	1/3819 (0%)	1
Drug administration error	1/3818 (0%)	1	0/3819 (0%)	0
Extra dose administered	0/3818 (0%)	0	1/3819 (0%)	1
Eye injury	0/3818 (0%)	0	1/3819 (0%)	1
Facial bones fracture	0/3818 (0%)	0	2/3819 (0.1%)	2
Fall	54/3818 (1.4%)	57	55/3819 (1.4%)	59
Femoral neck fracture	0/3818 (0%)	0	2/3819 (0.1%)	2
Femur fracture	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Fibula fracture	0/3818 (0%)	0	1/3819 (0%)	1
Foot fracture	2/3818 (0.1%)	2	4/3819 (0.1%)	4
Fracture	1/3818 (0%)	1	0/3819 (0%)	0
Gastrointestinal anastomotic leak	0/3818 (0%)	0	1/3819 (0%)	1
Gastrointestinal injury	1/3818 (0%)	1	0/3819 (0%)	0
Gastrointestinal stoma complication	1/3818 (0%)	1	0/3819 (0%)	0
Gastrostomy tube site complication	1/3818 (0%)	1	0/3819 (0%)	0
Hand fracture	1/3818 (0%)	1	0/3819 (0%)	0
Hip fracture	1/3818 (0%)	1	3/3819 (0.1%)	3
Humerus fracture	1/3818 (0%)	1	2/3819 (0.1%)	2
Ilium fracture	1/3818 (0%)	1	0/3819 (0%)	0
Incarcerated incisional hernia	0/3818 (0%)	0	1/3819 (0%)	1
Incision site haemorrhage	1/3818 (0%)	1	0/3819 (0%)	0
Incisional hernia	1/3818 (0%)	1	0/3819 (0%)	0
Injury	0/3818 (0%)	0	1/3819 (0%)	1
Intentional overdose	0/3818 (0%)	0	1/3819 (0%)	1
Joint dislocation	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Laceration	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Ligament rupture	1/3818 (0%)	1	0/3819 (0%)	0
Limb injury	0/3818 (0%)	0	1/3819 (0%)	1
Lower limb fracture	2/3818 (0.1%)	2	0/3819 (0%)	0
Meniscus injury	1/3818 (0%)	1	2/3819 (0.1%)	2
Multiple fractures	1/3818 (0%)	1	0/3819 (0%)	0
Multiple injuries	0/3818 (0%)	0	1/3819 (0%)	1
Muscle strain	1/3818 (0%)	1	1/3819 (0%)	1
Overdose	1/3818 (0%)	1	2/3819 (0.1%)	2
Pelvic fracture	0/3818 (0%)	0	3/3819 (0.1%)	3
Pneumothorax traumatic	1/3818 (0%)	1	0/3819 (0%)	0
Post concussion syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Post procedural complication	1/3818 (0%)	1	2/3819 (0.1%)	2
Post procedural haematoma	2/3818 (0.1%)	2	0/3819 (0%)	0
Post procedural haemorrhage	5/3818 (0.1%)	5	2/3819 (0.1%)	2
Post procedural myocardial infarction	2/3818 (0.1%)	2	0/3819 (0%)	0
Postoperative fever	1/3818 (0%)	1	0/3819 (0%)	0
Postoperative ileus	1/3818 (0%)	1	0/3819 (0%)	0
Postoperative respiratory failure	2/3818 (0.1%)	2	1/3819 (0%)	1
Postoperative thoracic procedure complication	0/3818 (0%)	0	1/3819 (0%)	1
Postoperative wound complication	0/3818 (0%)	0	1/3819 (0%)	1
Procedural complication	0/3818 (0%)	0	1/3819 (0%)	1
Procedural haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Procedural hypotension	1/3818 (0%)	1	0/3819 (0%)	0
Procedural intestinal perforation	1/3818 (0%)	1	0/3819 (0%)	0
Pulmonary contusion	0/3818 (0%)	0	1/3819 (0%)	1
Radius fracture	2/3818 (0.1%)	2	0/3819 (0%)	0
Rib fracture	4/3818 (0.1%)	4	2/3819 (0.1%)	2
Road traffic accident	20/3818 (0.5%)	21	18/3819 (0.5%)	18
Seroma	0/3818 (0%)	0	1/3819 (0%)	1
Spinal compression fracture	1/3818 (0%)	1	1/3819 (0%)	1
Spinal fracture	0/3818 (0%)	0	1/3819 (0%)	1
Stab wound	1/3818 (0%)	1	0/3819 (0%)	0
Stoma site reaction	1/3818 (0%)	1	0/3819 (0%)	0
Stress fracture	1/3818 (0%)	1	0/3819 (0%)	0
Subdural haematoma	5/3818 (0.1%)	5	4/3819 (0.1%)	4
Subdural haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Tendon rupture	1/3818 (0%)	1	1/3819 (0%)	1
Thermal burn	2/3818 (0.1%)	2	0/3819 (0%)	0
Thoracic vertebral fracture	1/3818 (0%)	1	0/3819 (0%)	0
Tibia fracture	0/3818 (0%)	0	2/3819 (0.1%)	2
Toxicity to various agents	1/3818 (0%)	1	1/3819 (0%)	1
Transfusion-related acute lung injury	0/3818 (0%)	0	1/3819 (0%)	1
Traumatic haematoma	0/3818 (0%)	0	1/3819 (0%)	1
Upper limb fracture	0/3818 (0%)	0	2/3819 (0.1%)	2
Ureteric injury	1/3818 (0%)	1	0/3819 (0%)	0
Vascular procedure complication	0/3818 (0%)	0	1/3819 (0%)	1
Vascular pseudoaneurysm	1/3818 (0%)	1	0/3819 (0%)	0
Wound	0/3818 (0%)	0	2/3819 (0.1%)	2
Wrist fracture	0/3818 (0%)	0	2/3819 (0.1%)	2
Wrong drug administered	1/3818 (0%)	1	0/3819 (0%)	0
Investigations
Arteriogram coronary	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Biopsy lung	0/3818 (0%)	0	1/3819 (0%)	1
Blood creatine phosphokinase increased	1/3818 (0%)	1	1/3819 (0%)	1
Blood creatinine increased	1/3818 (0%)	1	0/3819 (0%)	0
Blood glucose decreased	0/3818 (0%)	0	1/3819 (0%)	1
Blood glucose increased	1/3818 (0%)	1	2/3819 (0.1%)	2
Blood magnesium decreased	1/3818 (0%)	1	0/3819 (0%)	0
Blood potassium decreased	2/3818 (0.1%)	2	1/3819 (0%)	1
Blood potassium increased	0/3818 (0%)	0	1/3819 (0%)	1
Blood pressure increased	1/3818 (0%)	1	0/3819 (0%)	0
Cardiac monitoring	0/3818 (0%)	0	1/3819 (0%)	1
Catheterisation cardiac	1/3818 (0%)	1	0/3819 (0%)	0
Coagulation time prolonged	1/3818 (0%)	1	0/3819 (0%)	0
Ejection fraction decreased	1/3818 (0%)	1	0/3819 (0%)	0
Electrocardiogram ST segment abnormal	0/3818 (0%)	0	1/3819 (0%)	1
Electrocardiogram ST segment elevation	1/3818 (0%)	1	0/3819 (0%)	0
Electrocardiogram ST-T change	0/3818 (0%)	0	1/3819 (0%)	1
Hepatic enzyme increased	0/3818 (0%)	0	1/3819 (0%)	1
International normalised ratio increased	0/3818 (0%)	0	2/3819 (0.1%)	2
Medical observation	1/3818 (0%)	1	0/3819 (0%)	0
Troponin increased	1/3818 (0%)	1	2/3819 (0.1%)	2
Weight decreased	1/3818 (0%)	1	0/3819 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/3818 (0%)	1	1/3819 (0%)	1
Dehydration	23/3818 (0.6%)	23	16/3819 (0.4%)	16
Diabetes mellitus	1/3818 (0%)	1	4/3819 (0.1%)	4
Diabetes mellitus inadequate control	5/3818 (0.1%)	5	4/3819 (0.1%)	4
Diabetic complication	0/3818 (0%)	0	1/3819 (0%)	1
Diabetic ketoacidosis	5/3818 (0.1%)	5	14/3819 (0.4%)	14
Diabetic metabolic decompensation	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Electrolyte imbalance	2/3818 (0.1%)	2	1/3819 (0%)	1
Failure to thrive	1/3818 (0%)	1	0/3819 (0%)	0
Fluid overload	4/3818 (0.1%)	5	2/3819 (0.1%)	5
Gout	4/3818 (0.1%)	4	7/3819 (0.2%)	7
Hyperammonaemia	1/3818 (0%)	2	0/3819 (0%)	0
Hyperglycaemia	11/3818 (0.3%)	12	16/3819 (0.4%)	16
Hyperkalaemia	18/3818 (0.5%)	21	22/3819 (0.6%)	24
Hypernatraemia	0/3818 (0%)	0	1/3819 (0%)	1
Hypoglycaemia	64/3818 (1.7%)	77	49/3819 (1.3%)	66
Hypokalaemia	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Hypomagnesaemia	1/3818 (0%)	1	0/3819 (0%)	0
Hyponatraemia	8/3818 (0.2%)	8	7/3819 (0.2%)	7
Hypovolaemia	2/3818 (0.1%)	2	2/3819 (0.1%)	3
Lactic acidosis	1/3818 (0%)	1	2/3819 (0.1%)	2
Metabolic acidosis	3/3818 (0.1%)	3	1/3819 (0%)	1
Obesity	3/3818 (0.1%)	3	1/3819 (0%)	1
Pseudohyponatraemia	0/3818 (0%)	0	1/3819 (0%)	1
Type 2 diabetes mellitus	1/3818 (0%)	1	1/3819 (0%)	1
Musculoskeletal and connective tissue disorders
Ankle deformity	0/3818 (0%)	0	1/3819 (0%)	1
Arthralgia	5/3818 (0.1%)	6	8/3819 (0.2%)	9
Arthritis	3/3818 (0.1%)	3	7/3819 (0.2%)	8
Arthropathy	2/3818 (0.1%)	2	0/3819 (0%)	0
Back disorder	0/3818 (0%)	0	1/3819 (0%)	1
Back pain	7/3818 (0.2%)	7	12/3819 (0.3%)	12
Bursitis	0/3818 (0%)	0	3/3819 (0.1%)	3
Cervical spinal stenosis	5/3818 (0.1%)	5	3/3819 (0.1%)	3
Chondrocalcinosis pyrophosphate	0/3818 (0%)	0	2/3819 (0.1%)	2
Costochondritis	2/3818 (0.1%)	2	0/3819 (0%)	0
Dactylitis	1/3818 (0%)	1	0/3819 (0%)	0
Enthesopathy	1/3818 (0%)	1	0/3819 (0%)	0
Exostosis	1/3818 (0%)	1	0/3819 (0%)	0
Flank pain	1/3818 (0%)	1	2/3819 (0.1%)	2
Foot deformity	1/3818 (0%)	1	0/3819 (0%)	0
Gouty arthritis	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Haemarthrosis	0/3818 (0%)	0	1/3819 (0%)	1
Intervertebral disc degeneration	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Intervertebral disc disorder	1/3818 (0%)	1	1/3819 (0%)	1
Intervertebral disc protrusion	9/3818 (0.2%)	9	3/3819 (0.1%)	3
Joint effusion	0/3818 (0%)	0	1/3819 (0%)	1
Lumbar spinal stenosis	12/3818 (0.3%)	13	7/3819 (0.2%)	7
Muscle spasms	1/3818 (0%)	1	2/3819 (0.1%)	2
Muscular weakness	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Musculoskeletal chest pain	3/3818 (0.1%)	3	6/3819 (0.2%)	6
Musculoskeletal pain	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Myopathy	0/3818 (0%)	0	1/3819 (0%)	1
Neck pain	2/3818 (0.1%)	2	1/3819 (0%)	1
Osteitis	1/3818 (0%)	1	0/3819 (0%)	0
Osteoarthritis	32/3818 (0.8%)	35	30/3819 (0.8%)	31
Osteonecrosis	0/3818 (0%)	0	1/3819 (0%)	1
Osteopenia	1/3818 (0%)	1	0/3819 (0%)	0
Osteoporosis	1/3818 (0%)	2	0/3819 (0%)	0
Pain in extremity	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Polyarthritis	2/3818 (0.1%)	2	0/3819 (0%)	0
Polymyalgia rheumatica	0/3818 (0%)	0	1/3819 (0%)	1
Pseudarthrosis	0/3818 (0%)	0	1/3819 (0%)	1
Rhabdomyolysis	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Rotator cuff syndrome	2/3818 (0.1%)	2	2/3819 (0.1%)	3
Soft tissue necrosis	0/3818 (0%)	0	1/3819 (0%)	1
Spinal column stenosis	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Spinal osteoarthritis	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Spondylitis	0/3818 (0%)	0	1/3819 (0%)	1
Spondylolisthesis	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Synovial cyst	0/3818 (0%)	0	1/3819 (0%)	1
Tendon disorder	1/3818 (0%)	1	0/3819 (0%)	0
Tendonitis	1/3818 (0%)	1	1/3819 (0%)	1
Vertebral foraminal stenosis	1/3818 (0%)	1	1/3819 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	1/3818 (0%)	1	0/3819 (0%)	0
Acute lymphocytic leukaemia	1/3818 (0%)	1	0/3819 (0%)	0
Acute myeloid leukaemia	0/3818 (0%)	0	1/3819 (0%)	1
Adenocarcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Adenocarcinoma gastric	2/3818 (0.1%)	2	1/3819 (0%)	1
Adenocarcinoma of colon	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Adenocarcinoma pancreas	0/3818 (0%)	0	1/3819 (0%)	1
Adrenal adenoma	0/3818 (0%)	0	1/3819 (0%)	1
Adrenal neoplasm	0/3818 (0%)	0	1/3819 (0%)	1
Adult T-cell lymphoma/leukaemia	1/3818 (0%)	1	0/3819 (0%)	0
B-cell lymphoma	2/3818 (0.1%)	2	0/3819 (0%)	0
B-cell lymphoma stage III	0/3818 (0%)	0	1/3819 (0%)	1
Basal cell carcinoma	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Benign neoplasm of bladder	0/3818 (0%)	0	1/3819 (0%)	1
Benign neoplasm of thyroid gland	1/3818 (0%)	1	0/3819 (0%)	0
Benign ovarian tumour	0/3818 (0%)	0	1/3819 (0%)	1
Bile duct adenocarcinoma	1/3818 (0%)	1	0/3819 (0%)	0
Bladder cancer	1/3818 (0%)	1	3/3819 (0.1%)	3
Bladder cancer recurrent	1/3818 (0%)	1	0/3819 (0%)	0
Bladder cancer stage 0, with cancer in situ	1/3818 (0%)	1	0/3819 (0%)	0
Bladder transitional cell carcinoma	1/3818 (0%)	1	1/3819 (0%)	1
Bladder transitional cell carcinoma recurrent	2/3818 (0.1%)	2	0/3819 (0%)	0
Bladder transitional cell carcinoma stage I	1/3818 (0%)	1	0/3819 (0%)	0
Bone cancer	0/3818 (0%)	0	1/3819 (0%)	1
Bowen's disease	0/3818 (0%)	0	1/3819 (0%)	1
Brain neoplasm	1/3818 (0%)	1	0/3819 (0%)	0
Breast cancer	1/3818 (0%)	1	1/3819 (0%)	1
Breast cancer metastatic	1/3818 (0%)	1	1/3819 (0%)	1
Breast cancer stage I	0/3818 (0%)	0	2/3819 (0.1%)	2
Breast cancer stage II	1/3818 (0%)	1	0/3819 (0%)	0
Breast cancer stage IV	1/3818 (0%)	1	0/3819 (0%)	0
Cardiac valve fibroelastoma	0/3818 (0%)	0	1/3819 (0%)	1
Cholangiocarcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Choroid melanoma	1/3818 (0%)	1	0/3819 (0%)	0
Chronic myeloid leukaemia	0/3818 (0%)	0	1/3819 (0%)	1
Colon adenoma	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Colon cancer	2/3818 (0.1%)	2	1/3819 (0%)	1
Colon cancer metastatic	2/3818 (0.1%)	2	1/3819 (0%)	1
Colon cancer stage III	0/3818 (0%)	0	1/3819 (0%)	1
Colorectal cancer metastatic	0/3818 (0%)	0	1/3819 (0%)	1
Diffuse large B-cell lymphoma recurrent	0/3818 (0%)	0	1/3819 (0%)	1
Endometrial adenocarcinoma	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Fibroma	0/3818 (0%)	0	1/3819 (0%)	1
Gallbladder adenocarcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Gallbladder cancer metastatic	0/3818 (0%)	0	1/3819 (0%)	1
Gastrointestinal cancer metastatic	0/3818 (0%)	0	1/3819 (0%)	1
Gastrointestinal tract adenoma	1/3818 (0%)	1	0/3819 (0%)	0
Hepatic cancer	0/3818 (0%)	0	2/3819 (0.1%)	2
Hepatic cancer metastatic	0/3818 (0%)	0	2/3819 (0.1%)	2
Hepatic neoplasm	1/3818 (0%)	1	0/3819 (0%)	0
Hepatocellular carcinoma	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Intraductal proliferative breast lesion	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Invasive ductal breast carcinoma	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Leiomyoma	0/3818 (0%)	0	1/3819 (0%)	1
Leukaemia	0/3818 (0%)	0	1/3819 (0%)	1
Lipoma	1/3818 (0%)	1	1/3819 (0%)	1
Lung adenocarcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Lung adenocarcinoma metastatic	1/3818 (0%)	1	2/3819 (0.1%)	2
Lung adenocarcinoma stage II	1/3818 (0%)	1	1/3819 (0%)	1
Lung adenocarcinoma stage IV	0/3818 (0%)	0	1/3819 (0%)	1
Lung cancer metastatic	0/3818 (0%)	0	1/3819 (0%)	1
Lung neoplasm malignant	2/3818 (0.1%)	2	0/3819 (0%)	0
Lymphoma	1/3818 (0%)	1	1/3819 (0%)	1
Malignant melanoma	1/3818 (0%)	1	0/3819 (0%)	0
Malignant melanoma in situ	1/3818 (0%)	1	0/3819 (0%)	0
Malignant peritoneal neoplasm	1/3818 (0%)	1	0/3819 (0%)	0
Meningioma benign	3/3818 (0.1%)	3	0/3819 (0%)	0
Mesothelioma malignant	1/3818 (0%)	1	0/3819 (0%)	0
Metastases to bone	0/3818 (0%)	0	1/3819 (0%)	1
Metastases to central nervous system	0/3818 (0%)	0	1/3819 (0%)	1
Metastases to liver	1/3818 (0%)	1	2/3819 (0.1%)	2
Metastases to lung	0/3818 (0%)	0	1/3819 (0%)	1
Metastases to lymph nodes	0/3818 (0%)	0	1/3819 (0%)	1
Metastatic neoplasm	0/3818 (0%)	0	1/3819 (0%)	1
Metastatic renal cell carcinoma	3/3818 (0.1%)	3	0/3819 (0%)	0
Metastatic squamous cell carcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Mucinous endometrial carcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Myelodysplastic syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Neuroendocrine carcinoma metastatic	1/3818 (0%)	1	0/3819 (0%)	0
Non-small cell lung cancer	1/3818 (0%)	1	1/3819 (0%)	1
Non-small cell lung cancer metastatic	0/3818 (0%)	0	1/3819 (0%)	1
Non-small cell lung cancer stage I	0/3818 (0%)	0	1/3819 (0%)	1
Oesophageal adenocarcinoma	0/3818 (0%)	0	2/3819 (0.1%)	2
Oesophageal carcinoma	2/3818 (0.1%)	2	0/3819 (0%)	0
Ovarian cancer recurrent	1/3818 (0%)	1	0/3819 (0%)	0
Ovarian cancer stage IV	1/3818 (0%)	1	0/3819 (0%)	0
Pancreatic carcinoma	3/3818 (0.1%)	3	1/3819 (0%)	1
Pancreatic carcinoma metastatic	3/3818 (0.1%)	3	0/3819 (0%)	0
Pancreatic carcinoma stage IV	1/3818 (0%)	1	0/3819 (0%)	0
Papillary cystadenoma lymphomatosum	1/3818 (0%)	1	1/3819 (0%)	1
Papillary thyroid cancer	1/3818 (0%)	1	1/3819 (0%)	1
Parathyroid tumour benign	1/3818 (0%)	1	1/3819 (0%)	1
Penile squamous cell carcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Phaeochromocytoma	1/3818 (0%)	1	0/3819 (0%)	0
Pituitary tumour benign	1/3818 (0%)	1	0/3819 (0%)	0
Plasma cell myeloma	3/3818 (0.1%)	3	0/3819 (0%)	0
Prostate cancer	11/3818 (0.3%)	11	5/3819 (0.1%)	5
Prostate cancer metastatic	0/3818 (0%)	0	2/3819 (0.1%)	2
Prostate cancer stage I	0/3818 (0%)	0	3/3819 (0.1%)	3
Prostate cancer stage II	1/3818 (0%)	1	0/3819 (0%)	0
Rectal adenocarcinoma	2/3818 (0.1%)	2	0/3819 (0%)	0
Rectal adenoma	1/3818 (0%)	1	0/3819 (0%)	0
Rectal cancer	0/3818 (0%)	0	2/3819 (0.1%)	2
Rectal cancer metastatic	1/3818 (0%)	1	0/3819 (0%)	0
Renal cancer	2/3818 (0.1%)	2	0/3819 (0%)	0
Renal cancer metastatic	1/3818 (0%)	1	1/3819 (0%)	1
Renal cell carcinoma	1/3818 (0%)	1	3/3819 (0.1%)	3
Salivary gland cancer	0/3818 (0%)	0	1/3819 (0%)	1
Small cell lung cancer	2/3818 (0.1%)	2	1/3819 (0%)	1
Small cell lung cancer extensive stage	0/3818 (0%)	0	1/3819 (0%)	1
Small cell lung cancer metastatic	3/3818 (0.1%)	3	0/3819 (0%)	0
Soft tissue sarcoma	0/3818 (0%)	0	1/3819 (0%)	1
Squamous cell carcinoma	1/3818 (0%)	1	2/3819 (0.1%)	2
Squamous cell carcinoma of lung	2/3818 (0.1%)	2	1/3819 (0%)	1
Squamous cell carcinoma of skin	0/3818 (0%)	0	1/3819 (0%)	1
Squamous cell carcinoma of the tongue	0/3818 (0%)	0	1/3819 (0%)	1
Testicular seminoma (pure) stage I	0/3818 (0%)	0	1/3819 (0%)	1
Testis cancer	0/3818 (0%)	0	1/3819 (0%)	1
Thyroid cancer	1/3818 (0%)	1	0/3819 (0%)	0
Tonsil cancer	1/3818 (0%)	1	0/3819 (0%)	0
Transitional cell carcinoma	0/3818 (0%)	0	1/3819 (0%)	1
Tumour of ampulla of Vater	0/3818 (0%)	0	1/3819 (0%)	1
Ureteric cancer	0/3818 (0%)	0	1/3819 (0%)	1
Uterine cancer	2/3818 (0.1%)	2	1/3819 (0%)	1
Nervous system disorders
Altered state of consciousness	1/3818 (0%)	1	0/3819 (0%)	0
Aphasia	1/3818 (0%)	1	1/3819 (0%)	1
Ataxia	1/3818 (0%)	1	0/3819 (0%)	0
Balance disorder	0/3818 (0%)	0	1/3819 (0%)	1
Brain injury	3/3818 (0.1%)	3	0/3819 (0%)	0
Brain stem haemorrhage	0/3818 (0%)	0	2/3819 (0.1%)	2
Brain stem infarction	2/3818 (0.1%)	2	4/3819 (0.1%)	4
Brain stem stroke	0/3818 (0%)	0	1/3819 (0%)	1
Carotid artery disease	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Carotid artery occlusion	0/3818 (0%)	0	3/3819 (0.1%)	3
Carotid artery stenosis	15/3818 (0.4%)	15	14/3819 (0.4%)	15
Cerebellar infarction	1/3818 (0%)	1	3/3819 (0.1%)	3
Cerebral arteriosclerosis	1/3818 (0%)	1	0/3819 (0%)	0
Cerebral haemorrhage	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Cerebral infarction	5/3818 (0.1%)	5	4/3819 (0.1%)	5
Cerebral ischaemia	1/3818 (0%)	1	0/3819 (0%)	0
Cerebral small vessel ischaemic disease	1/3818 (0%)	1	0/3819 (0%)	0
Cerebrovascular accident	11/3818 (0.3%)	11	22/3819 (0.6%)	23
Cervical myelopathy	2/3818 (0.1%)	2	1/3819 (0%)	1
Cranial nerve paralysis	0/3818 (0%)	0	1/3819 (0%)	1
Dementia	2/3818 (0.1%)	2	1/3819 (0%)	1
Dementia Alzheimer's type	0/3818 (0%)	0	2/3819 (0.1%)	2
Diabetic mononeuropathy	0/3818 (0%)	0	1/3819 (0%)	1
Diabetic neuropathy	2/3818 (0.1%)	2	0/3819 (0%)	0
Dizziness	7/3818 (0.2%)	7	4/3819 (0.1%)	4
Dysarthria	1/3818 (0%)	1	1/3819 (0%)	1
Embolic cerebral infarction	0/3818 (0%)	0	1/3819 (0%)	1
Embolic stroke	4/3818 (0.1%)	4	2/3819 (0.1%)	2
Encephalopathy	6/3818 (0.2%)	6	4/3819 (0.1%)	4
Epidural lipomatosis	0/3818 (0%)	0	1/3819 (0%)	1
Essential tremor	0/3818 (0%)	0	1/3819 (0%)	1
Facial paralysis	1/3818 (0%)	1	1/3819 (0%)	1
Generalised tonic-clonic seizure	0/3818 (0%)	0	2/3819 (0.1%)	2
Guillain-Barre syndrome	1/3818 (0%)	1	1/3819 (0%)	1
Haemorrhage intracranial	1/3818 (0%)	1	3/3819 (0.1%)	3
Haemorrhagic cerebral infarction	1/3818 (0%)	1	0/3819 (0%)	0
Haemorrhagic stroke	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Haemorrhagic transformation stroke	0/3818 (0%)	0	1/3819 (0%)	1
Headache	4/3818 (0.1%)	4	6/3819 (0.2%)	6
Hemiparesis	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Hemiplegic migraine	1/3818 (0%)	1	0/3819 (0%)	0
Hepatic encephalopathy	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Hydrocephalus	1/3818 (0%)	2	1/3819 (0%)	1
Hyperglycaemic seizure	0/3818 (0%)	0	1/3819 (0%)	1
Hypertensive encephalopathy	0/3818 (0%)	0	1/3819 (0%)	1
Hypoaesthesia	0/3818 (0%)	0	1/3819 (0%)	1
Hypoglycaemic coma	1/3818 (0%)	1	1/3819 (0%)	2
Hypoglycaemic seizure	3/3818 (0.1%)	5	0/3819 (0%)	0
Hypoglycaemic unconsciousness	27/3818 (0.7%)	29	29/3819 (0.8%)	33
Hypoxic-ischaemic encephalopathy	1/3818 (0%)	1	1/3819 (0%)	1
IIIrd nerve paralysis	0/3818 (0%)	0	1/3819 (0%)	1
Intensive care unit acquired weakness	0/3818 (0%)	0	1/3819 (0%)	1
Intracranial aneurysm	1/3818 (0%)	1	0/3819 (0%)	0
Intracranial pressure increased	0/3818 (0%)	0	1/3819 (0%)	1
Ischaemic cerebral infarction	1/3818 (0%)	1	1/3819 (0%)	1
Ischaemic stroke	43/3818 (1.1%)	44	45/3819 (1.2%)	50
Lacunar infarction	5/3818 (0.1%)	5	2/3819 (0.1%)	2
Lacunar stroke	1/3818 (0%)	1	0/3819 (0%)	0
Lethargy	0/3818 (0%)	0	1/3819 (0%)	1
Loss of consciousness	4/3818 (0.1%)	4	4/3819 (0.1%)	4
Lumbar radiculopathy	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Memory impairment	1/3818 (0%)	1	0/3819 (0%)	0
Metabolic encephalopathy	7/3818 (0.2%)	7	9/3819 (0.2%)	10
Migraine	3/3818 (0.1%)	3	0/3819 (0%)	0
Migraine-triggered seizure	0/3818 (0%)	0	1/3819 (0%)	1
Mononeuropathy multiplex	0/3818 (0%)	0	1/3819 (0%)	1
Motor neurone disease	1/3818 (0%)	1	0/3819 (0%)	0
Multiple sclerosis relapse	0/3818 (0%)	0	1/3819 (0%)	2
Myasthenia gravis	0/3818 (0%)	0	1/3819 (0%)	1
Nerve root compression	1/3818 (0%)	1	0/3819 (0%)	0
Neuropathy peripheral	1/3818 (0%)	1	0/3819 (0%)	0
Normal pressure hydrocephalus	2/3818 (0.1%)	2	0/3819 (0%)	0
Paraesthesia	0/3818 (0%)	0	1/3819 (0%)	1
Parkinson's disease	1/3818 (0%)	1	4/3819 (0.1%)	4
Peripheral sensory neuropathy	1/3818 (0%)	1	0/3819 (0%)	0
Post-injection delirium sedation syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Presyncope	3/3818 (0.1%)	3	12/3819 (0.3%)	12
Radicular pain	0/3818 (0%)	0	1/3819 (0%)	1
Radiculopathy	0/3818 (0%)	0	2/3819 (0.1%)	2
Reversible ischaemic neurological deficit	1/3818 (0%)	1	0/3819 (0%)	0
Sciatica	0/3818 (0%)	0	2/3819 (0.1%)	2
Seizure	6/3818 (0.2%)	8	6/3819 (0.2%)	6
Senile dementia	0/3818 (0%)	0	1/3819 (0%)	1
Spinal cord compression	0/3818 (0%)	0	2/3819 (0.1%)	2
Spondylitic myelopathy	0/3818 (0%)	0	1/3819 (0%)	1
Status epilepticus	1/3818 (0%)	1	0/3819 (0%)	0
Subarachnoid haemorrhage	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Syncope	25/3818 (0.7%)	27	24/3819 (0.6%)	29
Thalamic infarction	1/3818 (0%)	1	3/3819 (0.1%)	3
Thalamus haemorrhage	1/3818 (0%)	1	1/3819 (0%)	1
Thrombotic stroke	1/3818 (0%)	1	0/3819 (0%)	0
Toxic encephalopathy	1/3818 (0%)	1	2/3819 (0.1%)	2
Transient global amnesia	0/3818 (0%)	0	1/3819 (0%)	1
Transient ischaemic attack	28/3818 (0.7%)	29	42/3819 (1.1%)	44
Tremor	0/3818 (0%)	0	1/3819 (0%)	1
Ulnar nerve palsy	1/3818 (0%)	1	0/3819 (0%)	0
VIth nerve paralysis	1/3818 (0%)	1	0/3819 (0%)	0
Vascular dementia	1/3818 (0%)	1	2/3819 (0.1%)	2
Vascular headache	0/3818 (0%)	0	1/3819 (0%)	1
Vertebrobasilar insufficiency	0/3818 (0%)	0	1/3819 (0%)	1
Visual field defect	0/3818 (0%)	0	1/3819 (0%)	1
Product Issues
Device dislocation	1/3818 (0%)	1	2/3819 (0.1%)	2
Device failure	1/3818 (0%)	1	0/3819 (0%)	0
Device fastener issue	1/3818 (0%)	1	0/3819 (0%)	0
Device inappropriate shock delivery	0/3818 (0%)	0	1/3819 (0%)	1
Device lead damage	0/3818 (0%)	0	1/3819 (0%)	1
Device loosening	0/3818 (0%)	0	1/3819 (0%)	1
Device malfunction	1/3818 (0%)	1	2/3819 (0.1%)	3
Lead dislodgement	1/3818 (0%)	2	1/3819 (0%)	1
Psychiatric disorders
Acute stress disorder	1/3818 (0%)	1	0/3819 (0%)	0
Affective disorder	1/3818 (0%)	1	1/3819 (0%)	1
Aggression	1/3818 (0%)	1	0/3819 (0%)	0
Agitation	1/3818 (0%)	1	0/3819 (0%)	0
Alcohol withdrawal syndrome	1/3818 (0%)	1	2/3819 (0.1%)	2
Anxiety	1/3818 (0%)	1	2/3819 (0.1%)	2
Bipolar disorder	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Completed suicide	0/3818 (0%)	0	2/3819 (0.1%)	2
Confusional state	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Delirium	2/3818 (0.1%)	2	5/3819 (0.1%)	5
Depression	5/3818 (0.1%)	5	4/3819 (0.1%)	4
Depression suicidal	1/3818 (0%)	1	1/3819 (0%)	1
Hallucination, visual	1/3818 (0%)	1	0/3819 (0%)	0
Intentional self-injury	1/3818 (0%)	1	0/3819 (0%)	0
Major depression	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Mental status changes	7/3818 (0.2%)	7	8/3819 (0.2%)	8
Paranoia	1/3818 (0%)	1	0/3819 (0%)	0
Personality change due to a general medical condition	1/3818 (0%)	1	0/3819 (0%)	0
Post stroke depression	0/3818 (0%)	0	1/3819 (0%)	1
Post-traumatic stress disorder	0/3818 (0%)	0	1/3819 (0%)	1
Psychotic disorder	0/3818 (0%)	0	1/3819 (0%)	1
Schizoaffective disorder	0/3818 (0%)	0	1/3819 (0%)	1
Schizoaffective disorder bipolar type	0/3818 (0%)	0	1/3819 (0%)	2
Schizophrenia	3/3818 (0.1%)	3	0/3819 (0%)	0
Suicidal ideation	5/3818 (0.1%)	6	3/3819 (0.1%)	3
Suicide attempt	0/3818 (0%)	0	3/3819 (0.1%)	3
Renal and urinary disorders
Acute kidney injury	70/3818 (1.8%)	79	95/3819 (2.5%)	110
Acute prerenal failure	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Anuria	0/3818 (0%)	0	2/3819 (0.1%)	2
Azotaemia	2/3818 (0.1%)	2	1/3819 (0%)	1
Bladder neck obstruction	0/3818 (0%)	0	1/3819 (0%)	1
Bladder outlet obstruction	1/3818 (0%)	1	0/3819 (0%)	0
Calculus bladder	1/3818 (0%)	1	0/3819 (0%)	0
Calculus urinary	0/3818 (0%)	0	1/3819 (0%)	1
Chronic kidney disease	16/3818 (0.4%)	18	26/3819 (0.7%)	30
Cystitis noninfective	1/3818 (0%)	1	0/3819 (0%)	0
Diabetic nephropathy	1/3818 (0%)	1	3/3819 (0.1%)	3
End stage renal disease	12/3818 (0.3%)	12	9/3819 (0.2%)	9
Glomerulonephritis rapidly progressive	1/3818 (0%)	1	0/3819 (0%)	0
Haematuria	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Hydronephrosis	2/3818 (0.1%)	2	3/3819 (0.1%)	3
Nephrolithiasis	11/3818 (0.3%)	11	9/3819 (0.2%)	9
Nephropathy	0/3818 (0%)	0	1/3819 (0%)	1
Nephropathy toxic	0/3818 (0%)	0	1/3819 (0%)	1
Nephrosclerosis	1/3818 (0%)	1	0/3819 (0%)	0
Nephrotic syndrome	1/3818 (0%)	1	2/3819 (0.1%)	2
Renal artery stenosis	0/3818 (0%)	0	1/3819 (0%)	1
Renal colic	0/3818 (0%)	0	1/3819 (0%)	1
Renal failure	14/3818 (0.4%)	14	17/3819 (0.4%)	17
Renal impairment	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Renal mass	1/3818 (0%)	1	0/3819 (0%)	0
Renal tubular necrosis	0/3818 (0%)	0	1/3819 (0%)	1
Stag horn calculus	2/3818 (0.1%)	2	0/3819 (0%)	0
Stress urinary incontinence	2/3818 (0.1%)	2	0/3819 (0%)	0
Tubulointerstitial nephritis	0/3818 (0%)	0	1/3819 (0%)	1
Ureterolithiasis	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Urethral stenosis	1/3818 (0%)	1	0/3819 (0%)	0
Urinary hesitation	1/3818 (0%)	1	0/3819 (0%)	0
Urinary retention	9/3818 (0.2%)	9	2/3819 (0.1%)	2
Reproductive system and breast disorders
Balanoposthitis	1/3818 (0%)	1	1/3819 (0%)	1
Benign prostatic hyperplasia	9/3818 (0.2%)	9	7/3819 (0.2%)	7
Breast enlargement	1/3818 (0%)	1	0/3819 (0%)	0
Cervical cyst	1/3818 (0%)	1	0/3819 (0%)	0
Cervical dysplasia	0/3818 (0%)	0	2/3819 (0.1%)	2
Cervix haemorrhage uterine	1/3818 (0%)	1	0/3819 (0%)	0
Cystocele	2/3818 (0.1%)	2	0/3819 (0%)	0
Endometrial hyperplasia	3/3818 (0.1%)	3	0/3819 (0%)	0
Ovarian cyst	1/3818 (0%)	1	0/3819 (0%)	0
Prostatitis	1/3818 (0%)	1	1/3819 (0%)	1
Prostatomegaly	0/3818 (0%)	0	1/3819 (0%)	1
Rectocele	1/3818 (0%)	1	0/3819 (0%)	0
Uterine mass	1/3818 (0%)	1	0/3819 (0%)	0
Uterine prolapse	0/3818 (0%)	0	1/3819 (0%)	1
Vaginal haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Respiratory, thoracic and mediastinal disorders
Acquired diaphragmatic eventration	0/3818 (0%)	0	1/3819 (0%)	1
Acute pulmonary oedema	6/3818 (0.2%)	9	6/3819 (0.2%)	6
Acute respiratory distress syndrome	3/3818 (0.1%)	3	0/3819 (0%)	0
Acute respiratory failure	24/3818 (0.6%)	26	31/3819 (0.8%)	35
Asthma	6/3818 (0.2%)	7	8/3819 (0.2%)	8
Asthma-chronic obstructive pulmonary disease overlap syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Atelectasis	1/3818 (0%)	1	4/3819 (0.1%)	4
Bronchial hyperreactivity	0/3818 (0%)	0	1/3819 (0%)	1
Chronic obstructive pulmonary disease	42/3818 (1.1%)	54	56/3819 (1.5%)	70
Chronic respiratory failure	2/3818 (0.1%)	2	0/3819 (0%)	0
Cough	2/3818 (0.1%)	2	1/3819 (0%)	1
Dyspnoea	11/3818 (0.3%)	11	17/3819 (0.4%)	19
Dyspnoea exertional	4/3818 (0.1%)	4	1/3819 (0%)	1
Dyspnoea paroxysmal nocturnal	0/3818 (0%)	0	1/3819 (0%)	1
Epistaxis	1/3818 (0%)	1	3/3819 (0.1%)	4
Haemothorax	1/3818 (0%)	1	0/3819 (0%)	0
Hypoxia	3/3818 (0.1%)	3	8/3819 (0.2%)	8
Idiopathic pulmonary fibrosis	1/3818 (0%)	1	0/3819 (0%)	0
Interstitial lung disease	1/3818 (0%)	1	3/3819 (0.1%)	3
Laryngeal stenosis	1/3818 (0%)	1	0/3819 (0%)	0
Nasal polyps	1/3818 (0%)	1	1/3819 (0%)	1
Nasal septum deviation	1/3818 (0%)	1	1/3819 (0%)	1
Non-cardiogenic pulmonary oedema	1/3818 (0%)	1	0/3819 (0%)	0
Obstructive airways disorder	1/3818 (0%)	1	0/3819 (0%)	0
Pharyngeal oedema	2/3818 (0.1%)	2	0/3819 (0%)	0
Pickwickian syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Pleural effusion	1/3818 (0%)	1	6/3819 (0.2%)	6
Pleurisy	0/3818 (0%)	0	3/3819 (0.1%)	3
Pleuritic pain	0/3818 (0%)	0	1/3819 (0%)	1
Pneumonia aspiration	1/3818 (0%)	1	3/3819 (0.1%)	3
Pneumonitis	0/3818 (0%)	0	1/3819 (0%)	1
Pneumothorax	3/3818 (0.1%)	3	1/3819 (0%)	1
Pneumothorax spontaneous	0/3818 (0%)	0	1/3819 (0%)	1
Pulmonary congestion	1/3818 (0%)	1	1/3819 (0%)	1
Pulmonary embolism	15/3818 (0.4%)	15	10/3819 (0.3%)	10
Pulmonary fibrosis	1/3818 (0%)	1	1/3819 (0%)	1
Pulmonary hypertension	6/3818 (0.2%)	6	5/3819 (0.1%)	5
Pulmonary mass	1/3818 (0%)	1	2/3819 (0.1%)	2
Pulmonary oedema	6/3818 (0.2%)	6	9/3819 (0.2%)	9
Pulmonary sarcoidosis	0/3818 (0%)	0	1/3819 (0%)	1
Pulmonary veno-occlusive disease	0/3818 (0%)	0	1/3819 (0%)	1
Respiratory distress	2/3818 (0.1%)	2	2/3819 (0.1%)	2
Respiratory failure	22/3818 (0.6%)	23	18/3819 (0.5%)	19
Respiratory tract inflammation	0/3818 (0%)	0	1/3819 (0%)	1
Sleep apnoea syndrome	0/3818 (0%)	0	7/3819 (0.2%)	7
Upper respiratory tract inflammation	0/3818 (0%)	0	1/3819 (0%)	1
Skin and subcutaneous tissue disorders
Angioedema	3/3818 (0.1%)	4	8/3819 (0.2%)	9
Decubitus ulcer	1/3818 (0%)	1	2/3819 (0.1%)	2
Dermal cyst	1/3818 (0%)	1	0/3819 (0%)	0
Dermatitis	1/3818 (0%)	1	0/3819 (0%)	0
Diabetic foot	10/3818 (0.3%)	10	11/3819 (0.3%)	11
Diabetic neuropathic ulcer	0/3818 (0%)	0	1/3819 (0%)	1
Eczema	1/3818 (0%)	1	0/3819 (0%)	0
Hidradenitis	1/3818 (0%)	1	0/3819 (0%)	0
Hyperhidrosis	1/3818 (0%)	1	0/3819 (0%)	0
Hypersensitivity vasculitis	1/3818 (0%)	1	0/3819 (0%)	0
Neuropathic ulcer	2/3818 (0.1%)	2	1/3819 (0%)	1
Pemphigoid	0/3818 (0%)	0	1/3819 (0%)	1
Rash	1/3818 (0%)	1	0/3819 (0%)	0
Skin necrosis	0/3818 (0%)	0	1/3819 (0%)	1
Skin ulcer	13/3818 (0.3%)	13	6/3819 (0.2%)	6
Skin ulcer haemorrhage	0/3818 (0%)	0	1/3819 (0%)	1
Stasis dermatitis	2/3818 (0.1%)	2	0/3819 (0%)	0
Urticaria	1/3818 (0%)	1	0/3819 (0%)	0
Social circumstances
Social stay hospitalisation	1/3818 (0%)	1	0/3819 (0%)	0
Surgical and medical procedures
Abdominal hernia repair	0/3818 (0%)	0	1/3819 (0%)	1
Abdominal panniculectomy	1/3818 (0%)	1	0/3819 (0%)	0
Amputation	0/3818 (0%)	0	1/3819 (0%)	1
Angioplasty	2/3818 (0.1%)	2	0/3819 (0%)	0
Aortic aneurysm repair	0/3818 (0%)	0	1/3819 (0%)	1
Aortic stent insertion	1/3818 (0%)	1	0/3819 (0%)	0
Aortic valve replacement	1/3818 (0%)	1	0/3819 (0%)	0
Arteriovenous fistula operation	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac ablation	1/3818 (0%)	1	2/3819 (0.1%)	2
Cardiac pacemaker battery replacement	0/3818 (0%)	0	1/3819 (0%)	1
Cardiac pacemaker insertion	1/3818 (0%)	1	1/3819 (0%)	1
Cardiac pacemaker replacement	0/3818 (0%)	0	4/3819 (0.1%)	4
Cataract operation	1/3818 (0%)	1	1/3819 (0%)	1
Colectomy	1/3818 (0%)	1	0/3819 (0%)	0
Colostomy closure	1/3818 (0%)	1	0/3819 (0%)	0
Coronary arterial stent insertion	0/3818 (0%)	0	1/3819 (0%)	1
Coronary artery bypass	1/3818 (0%)	1	2/3819 (0.1%)	2
Duodenal switch	1/3818 (0%)	1	0/3819 (0%)	0
Gastrectomy	4/3818 (0.1%)	4	3/3819 (0.1%)	3
Gastric bypass	3/3818 (0.1%)	3	4/3819 (0.1%)	4
Hernia repair	1/3818 (0%)	1	0/3819 (0%)	0
Hip arthroplasty	2/3818 (0.1%)	2	0/3819 (0%)	0
Hysterectomy	1/3818 (0%)	1	0/3819 (0%)	0
Implantable defibrillator insertion	2/3818 (0.1%)	2	1/3819 (0%)	1
Implantable defibrillator replacement	0/3818 (0%)	0	1/3819 (0%)	1
Inguinal hernia repair	2/3818 (0.1%)	2	1/3819 (0%)	1
Intervertebral disc operation	1/3818 (0%)	1	0/3819 (0%)	0
Intra-ocular injection	1/3818 (0%)	1	0/3819 (0%)	0
Jejunostomy	0/3818 (0%)	0	1/3819 (0%)	1
Joint arthroplasty	1/3818 (0%)	1	0/3819 (0%)	0
Knee arthroplasty	4/3818 (0.1%)	5	7/3819 (0.2%)	8
Knee operation	1/3818 (0%)	1	0/3819 (0%)	0
Leg amputation	0/3818 (0%)	0	1/3819 (0%)	1
Metabolic surgery	0/3818 (0%)	0	1/3819 (0%)	1
Oesophagectomy	0/3818 (0%)	0	1/3819 (0%)	1
Rotator cuff repair	0/3818 (0%)	0	1/3819 (0%)	1
Roux loop conversion	0/3818 (0%)	0	1/3819 (0%)	1
Spinal decompression	0/3818 (0%)	0	1/3819 (0%)	1
Spinal fusion surgery	1/3818 (0%)	1	0/3819 (0%)	0
Spinal laminectomy	2/3818 (0.1%)	2	0/3819 (0%)	0
Thyroidectomy	0/3818 (0%)	0	1/3819 (0%)	1
Transurethral prostatectomy	0/3818 (0%)	0	1/3819 (0%)	1
Umbilical hernia repair	1/3818 (0%)	1	0/3819 (0%)	0
Vascular disorders
Accelerated hypertension	4/3818 (0.1%)	4	7/3819 (0.2%)	7
Aneurysm	0/3818 (0%)	0	1/3819 (0%)	1
Angiopathy	0/3818 (0%)	0	1/3819 (0%)	1
Aortic aneurysm	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Aortic stenosis	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Arterial haemorrhage	0/3818 (0%)	0	2/3819 (0.1%)	2
Arteriosclerosis	3/3818 (0.1%)	3	2/3819 (0.1%)	2
Blood pressure inadequately controlled	1/3818 (0%)	1	0/3819 (0%)	0
Deep vein thrombosis	13/3818 (0.3%)	13	10/3819 (0.3%)	10
Dry gangrene	2/3818 (0.1%)	2	1/3819 (0%)	1
Embolism	1/3818 (0%)	1	0/3819 (0%)	0
Embolism arterial	0/3818 (0%)	0	2/3819 (0.1%)	2
Embolism venous	1/3818 (0%)	1	1/3819 (0%)	1
Essential hypertension	1/3818 (0%)	1	0/3819 (0%)	0
Extremity necrosis	1/3818 (0%)	1	3/3819 (0.1%)	3
Hypertension	17/3818 (0.4%)	19	23/3819 (0.6%)	24
Hypertensive crisis	8/3818 (0.2%)	8	8/3819 (0.2%)	8
Hypertensive emergency	3/3818 (0.1%)	3	3/3819 (0.1%)	3
Hypotension	14/3818 (0.4%)	14	14/3819 (0.4%)	15
Hypovolaemic shock	0/3818 (0%)	0	2/3819 (0.1%)	2
Intermittent claudication	2/3818 (0.1%)	2	6/3819 (0.2%)	6
Ischaemic limb pain	0/3818 (0%)	0	1/3819 (0%)	1
Leriche syndrome	0/3818 (0%)	0	1/3819 (0%)	1
Lymphocele	0/3818 (0%)	0	1/3819 (0%)	1
Malignant hypertension	3/3818 (0.1%)	3	5/3819 (0.1%)	5
Microangiopathy	1/3818 (0%)	1	0/3819 (0%)	0
Obstructive shock	1/3818 (0%)	1	0/3819 (0%)	0
Orthostatic hypotension	6/3818 (0.2%)	6	8/3819 (0.2%)	8
Peripheral arterial occlusive disease	13/3818 (0.3%)	13	12/3819 (0.3%)	12
Peripheral artery aneurysm	1/3818 (0%)	1	1/3819 (0%)	1
Peripheral artery occlusion	4/3818 (0.1%)	4	4/3819 (0.1%)	5
Peripheral artery stenosis	2/3818 (0.1%)	3	4/3819 (0.1%)	4
Peripheral artery thrombosis	1/3818 (0%)	1	0/3819 (0%)	0
Peripheral embolism	0/3818 (0%)	0	1/3819 (0%)	1
Peripheral ischaemia	3/3818 (0.1%)	3	7/3819 (0.2%)	7
Peripheral vascular disorder	11/3818 (0.3%)	12	14/3819 (0.4%)	17
Peripheral venous disease	0/3818 (0%)	0	2/3819 (0.1%)	2
Phlebitis	0/3818 (0%)	0	1/3819 (0%)	1
Reperfusion injury	0/3818 (0%)	0	1/3819 (0%)	1
Shock haemorrhagic	0/3818 (0%)	0	2/3819 (0.1%)	2
Subclavian steal syndrome	1/3818 (0%)	1	0/3819 (0%)	0
Superior vena cava stenosis	0/3818 (0%)	0	1/3819 (0%)	1
Temporal arteritis	1/3818 (0%)	1	0/3819 (0%)	0
Thrombosis	4/3818 (0.1%)	4	2/3819 (0.1%)	4
Vascular insufficiency	0/3818 (0%)	0	1/3819 (0%)	3
Other (Not Including Serious) Adverse Events
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3818 (0%)		0/3819 (0%)

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"