A 38 Week Trial Comparing Effect and Safety of Insulin De... | NCT02906917

ID	Type	Description	Link
2015-004768-12	EudraCT Number
U1111-1175-7895	Other Identifier	WHO

Label	Type	Description	Intervention Names
IDegAsp	Experimental		Drug: Insulin degludec/insulin aspart
IGlar + IAsp	Active Comparator		Drug: Insulin glargine Drug: Insulin aspart

Name	Type	Description	Arm Group Labels	Other Names
Insulin degludec/insulin aspart	Drug	Administered subcutaneously (s.c. under the skin) once daily.	IDegAsp

Measure	Description	Time Frame
Change in HbA1c (%) - Week 26	Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation.	Week 0, week 26

Measure	Description	Time Frame
Change in HbA1c (%) - Week 38	Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation.	Week 0, week 38
Responder (Yes/No) for HbA1c < 7%	Participants achieving (yes/no) HbA1c <7% was evaluated 26 and 38 weeks after randomisation, respectively.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
Male or female, age at least 18 years at the time of signing informed consent Algeria: Male or female, age at least 19 years at the time of signing informed consent
Diagnosed with type 2 diabetes mellitus
Treated with any basal insulin for at least 90 days prior to the day of screening
Subject not on any OAD(s) prior to trial participation OR subjects on stable daily dose(s) of OAD(s) for at least 90 days prior to screening visit (V1). The OAD(s) include any of the following anti-diabetic drug s)/regimen: a. Biguanides (metformin at least 1500 mg or maximum tolerated dose documented in the subject medical record) b. Other OADs (at least half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record): i. Insulin secretagogues (SU and glinides) ii. Di-peptidyl-peptidase IV (DPP-4) inhibitors iii. α-glucosidase inhibitors iv. Sodium/glucose co-transporter 2 (SGLT-2) inhibitors v. Oral combination products (of the allowed individual OADs above)
HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) by central laboratory analysis
Body mass index (BMI) equal to or below 45.0 kg/m^2

Exclusion Criteria:

Participation in any clinical trial of an approved or non-approved investigational medicinal product within four weeks prior to the day of screening (V1)
Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol
Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g. diabetes ketoacidosis) equal or below 90 days prior to the day of the screening and between screening and randomisation
Any of the following: myocardial infarction, stroke or hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and between screening and randomisation
Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of below 60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening
Impaired liver function, defined as alanine aminotransferase (ALT) equal to or above 2.5 times upper normal limit (UNL) at screening.
Subjects presently classified as being in New York Heart Association (NYHA) Class IV
Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening
Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids)

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Glendale	Arizona	85306-4652	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
30448451	Result	Philis-Tsimikas A, Astamirova K, Gupta Y, Haggag A, Roula D, Bak BA, Fita EG, Nielsen AM, Demir T. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2019 Jan;147:157-165. doi: 10.1016/j.diabres.2018.10.024. Epub 2018 Nov 16.
35044568

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin degludec/insulin aspart (IDegAsp) once daily (OD) administered at the largest meal each day with or without oral antidiabetic drug(s) (OAD(s)). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/twice a day (BID) administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 22, 2018	Aug 28, 2018

Arm/Group Information

ID	Title	Description
BG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
BG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in HbA1c (%) - Week 26

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Mean

Standard Deviation

% of HbA1c

Week 0, week 26

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Units	Counts
Participants	OG000267 OG001265

Title

Denominators

Categories

Baseline (week 0)

- ParticipantsOG000261
- ParticipantsOG001264

Title	Measurements
	OG0008.2± 0.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The response and change from baseline in response are analysed on 1000 complete, imputed data sets after multiple imputation for each treatment arm separately. A penalty of 0.4% is added to the week 26 values for all premature treatment discontinued subjects, and subject with missing HbA1c values at week 26 in the IDegAsp arm. Each of the imputed data sets are analysed through an analysis of covariance (ANCOVA).	ANCOVA	Treatment, region, sex, previous insulin treatment and previous OAD treatment as categorical fixed effects and baseline response and age as covariate.	<0.0001	One-sided p-value for test of non-inferiority.	Treatment contrast	0.07			2-Sided	95	-0.06	0.21

Secondary

Change in HbA1c (%) - Week 38

Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Mean

Standard Deviation

% of HbA1c

Week 0, week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Responder (Yes/No) for HbA1c < 7%

Participants achieving (yes/no) HbA1c <7% was evaluated 26 and 38 weeks after randomisation, respectively.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Number

Number of participants

Week 26 and week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia

Participants achieving (yes/no) HbA1c <7% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia, was evaluated 26 and 38 weeks after randomisation, respectively. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Number

Number of participants

Week 26 and week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).

Secondary

Change in FPG

Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated 26 and 38 weeks after randomisation, respectively.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Mean

Standard Deviation

mg/dL

Week 0, week 26, week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Change in Pre-breakfast SMPG (Used for Titration)

Reported results are observed pre-breakfast self-measured plasma glucose (SMPG; used for titration) values at week 1 (baseline) and 26 and 38 weeks after randomisation.

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Mean

Standard Deviation

mg/dL

Week 1, week 26, week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Change in Postprandial SMPG Increment (From 9-point Profile)

Change from baseline (week 0) in postprandial SMPG increment (from 9-point profile) was evaluated 26 and 38 weeks after randomisation, respectively. 9-point SMPG profiles were measured starting in the morning 2 days prior to the scheduled visit at the time points described below: 1) Before breakfast (2 days prior to visit) 2) 90 minutes after start of the breakfast 3) Before lunch 4) 90 minutes after start of the lunch 5) Before dinner/main evening meal 6) 90 minutes after start of the dinner/main evening meal 7) At bedtime (2 days or 1 day prior to visit depending on actual clock time) 8) At 4 a.m. (1 day prior to visit) 9) Before breakfast at the following day (1 day prior to the visit).

FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Mean

Standard Deviation

mg/dL

Week 0, week 26, week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart

Secondary

Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes

Number of nocturnal, treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Nocturnal hypoglycaemic episodes: episodes occurring between 00:01 and 05:59 both inclusive. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.

Safety analysis set, which included all subjects receiving at least one dose of the investigational product (IDegAsp) or comparator (IGlar). Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Number

Episodes

Weeks 0-26, weeks 16-26, weeks 0-38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart

Secondary

Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes

Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.

Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Posted

Number

Episodes

Weeks 0-26, weeks 16-26, weeks 0-38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Total Insulin Dose

Total insulin dose was evaluated 26 and 38 weeks after randomisation, respectively.

Posted

Mean

Standard Deviation

Units

Week 26 and week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Change in Body Weight

Change from baseline (week 0) in body weight was evaluated 26 and 38 weeks after randomisation, respectively.

Posted

Mean

Standard Deviation

Week 0, week 26, week 38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).

Secondary

Incidence of TEAEs

Number of treatment emergent adverse events (TEAEs) were analysed during the following periods: weeks 0-26, weeks 26-38 and weeks 0-38. Treatment emergent: An adverse event that had an onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. If an event had an onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period, or if it had an onset date within 7 days after the last drug date, then this event was also to be considered as a TEAE.

Posted

Number

Events

Weeks 0-26, weeks 26-38, weeks 0-38

ID	Title	Description
OG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).
OG001	Insulin Glargine + Insulin Aspart

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Insulin Degludec/Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	0	265	18	265	74	265
EG001	Insulin Glargine + Insulin Aspart	Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).	2	263	20	263	57	263

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0011 events1 affected263 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Adrenal mass	Endocrine disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Appendicitis	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Bronchitis	Infections and infestations	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Cholecystectomy	Surgical and medical procedures	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Colitis	Gastrointestinal disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Coronary artery disease	Cardiac disorders	MedDRA 20	Systematic Assessment	EG0002 events2 affected265 at risk EG0011 events1 affected263 at risk
Epiglottitis	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Facial paralysis	Nervous system disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Furuncle	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Hernia repair	Surgical and medical procedures	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Hidradenitis	Skin and subcutaneous tissue disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Infected skin ulcer	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Meningitis viral	Infections and infestations	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0011 events1 affected263 at risk
Non-cardiac chest pain	General disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0012 events2 affected263 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Peritonitis	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Peritonsillar abscess	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Pituitary tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Pneumonia	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0011 events1 affected263 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Tubulointerstitial nephritis	Renal and urinary disorders	MedDRA 20	Systematic Assessment	EG0001 events1 affected265 at risk EG0010 events0 affected263 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0011 events1 affected263 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 20	Systematic Assessment	EG0000 events0 affected265 at risk EG0012 events2 affected263 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D061266	Insulin, Short-Acting

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20	Systematic Assessment	EG00017 events16 affected265 at risk EG0019 events9 affected263 at risk
Headache	Nervous system disorders	MedDRA 20	Systematic Assessment	EG00052 events27 affected265 at risk EG00123 events16 affected263 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20	Systematic Assessment	EG00049 events36 affected265 at risk EG00127 events22 affected263 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20	Systematic Assessment	EG00017 events15 affected265 at risk EG00117 events17 affected263 at risk

ID	Term
C578220	insulin degludec, insulin aspart drug combination
D000069036	Insulin Glargine
D061267	Insulin Aspart