A Research Study to Compare Two Types of Insulin, a New I... | NCT04795531

NCT04795531

ID	Type	Description	Link
U1111-1247-5218	Other Identifier	World Health Organization (WHO)
2020-000472-37	EudraCT Number

Description Module

Label	Type	Description	Intervention Names
Once weekly insulin icodec + once daily placebo	Experimental	Participants will get once daily and once weekly injections	Drug: Insulin icodec Drug: Placebo insulin degludec
Once weekly placebo and once daily insulin degludec	Experimental	Participants will get once daily and once weekly injections	Drug: Placebo insulin icodec Drug: Insulin degludec

Name	Type	Description	Arm Group Labels	Other Names
Insulin icodec	Drug	You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo. Subcutaneously (under the skin) injections

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Glycated Haemoglobin (HbA1c)	Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome data is evaluated based on the in-trial observation period. The in-trial period started at randomisation and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for participants who died before any of the above.	Baseline (Week 0), Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change in Fasting Plasma Glucose (FPG)	Change in FPG from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomisation and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for participants who died before any of the above.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female aged above or equal to 18 years at the time of signing informed consent.
Diagnosed with T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
HbA1c (glycated haemoglobin) from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
Stable daily dose(s) greater than or equal to 90 days prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s):

a.) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b.) Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c.) Any of the following oral anti-diabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose).:Sulfonylureas - Meglitinides (glinides) - DPP-4 inhibitors - SGLT2 inhibitors - Thiazolidinediones - Alpha-glucosidase inhibitors - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - Oral or injectable GLP-1-receptor agonists
Body mass index (BMI) below or equal to 40.0 kg/m^2.

Exclusion Criteria:

Any episodes (as declared by the subject or in the medical records) of diabetic ketoacidosis within 90 days prior to the day of screening.
Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
Chronic heart failure classified as being in New York Heart Association (NYHA) Class IV at 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).
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Name	Affiliation	Role
Clinical Transparency (dept. 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Univ of Alabama Birmingham		Birmingham	Alabama	35222	United States
Lakeview Clinical Research, LLC

PubMed Identifier	Type	Citation	Retractions
36106652	Result	Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.
40465144

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.

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	Nov 30, 2020	Nov 10, 2024

Arm/Group Information

ID	Title	Description
BG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
BG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.
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 Glycated Haemoglobin (HbA1c)

Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome data is evaluated based on the in-trial observation period. The in-trial period started at randomisation and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for participants who died before any of the above.

Full analysis set (FAS) included all randomised participants.

Posted

Least Squares Mean

Standard Error

Percentage of HbA1c

Baseline (Week 0), Week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.

Units	Counts
Participants	OG000294 OG001294

Title

Denominators

Categories

Title	Measurements
	OG000-1.57± 0.05 OG001-1.36± 0.05

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 after 26 weeks are analysed using an analysis of covariance (ANCOVA) model with treatment, region and sulfonylureas (SU)/glinides use as fixed factors, and baseline response as covariate.	ANCOVA		<0.0001		Treatment difference	-0.21			2-Sided	95	-0.34	-0.08					Non-Inferiority	Non-inferiority of insulin icodec was considered confirmed if the upper limit of the two-sided 95% confidence interval (CI) for mean treatment difference (insulin icodec minus insulin degludec) was strictly below 0.3%.

Secondary

Change in Fasting Plasma Glucose (FPG)

Change in FPG from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomisation and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for participants who died before any of the above.

Full analysis set (FAS) included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

millimoles per liter (mmol/L)

Baseline (Week 0), Week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec

Secondary

Number of Severe Hypoglycaemic Episodes (Level 3)

Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the on-tratment period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a participant was considered exposed to trial product.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 31

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.

Secondary

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (< 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose [BG] Meter)

Number of clinically significant hypoglycaemic episodes (level 2) (less than [<] 3.0 millimoles per liter (mmol/L) (54 mg/dL), confirmed by BG meter) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than 3.0 mmol/L (54 mg/dL) confirmed by BG meter. The outcome data was evaluated based on the on-treatment period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a participant was considered exposed to trial product.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 31

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.

Secondary

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)

Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L) (54 mg/dL), confirmed by blood glucose [BG] meter) or severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. The outcome data was evaluated based on the on-treatment period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 31

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.

Secondary

Number of Severe Hypoglycaemic Episodes (Level 3)

Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.

Secondary

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)

Number of clinically significant hypoglycaemic episodes (level 2) (< 3.0 mmol/L (54 mg/dL), confirmed by BG meter) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.

Secondary

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)

Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 millimoles per liter (mmol/L) (54 milligrams per deciliter [mg/dL]) confirmed by blood glucose (BG) meter.

Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Posted

Number

Episodes

From baseline (week 0) to week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec

Secondary

Change in Body Weight

Change in body weight from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomisation and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for participants who died before any of the above.

Full analysis set included all randomised participants.

Posted

Least Squares Mean

Standard Error

Kilograms (kg)

Baseline (Week 0), Week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.

Secondary

Mean Weekly Insulin Dose

Estimated mean weekly insulin dose during the last 2 weeks of treatment (from week 24 to week 26) is presented. The outcome data was evaluated based on the on-treatment period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a participant was considered exposed to trial product.

Full analysis set included all randomised participants.

Posted

Least Squares Mean

95% Confidence Interval

Units (U) of insulin

From week 24 to week 26

ID	Title	Description
OG000	Insulin Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.
OG001

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 Icodec	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin icodec using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once weekly placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 20 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 20 U.	2	293	15	293	52	293
EG001	Insulin Degludec	Participants were to receive once daily s.c. injection of insulin degludec using PDS290 prefilled pen-injector at a starting dose of 10 U and once daily placebo for 26 weeks. The dose was then adjusted once weekly to reach the glycaemic target of 4.4-7.2 millimoles per liter mmol/L based on 3 pre-breakfast values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose reduced by 3 U; If the mean was: 4.4-7.2 mmol/L- no adjustment; > 7.2 mmol/L- dose increased by 3 U.	1	294	15	294	29	294

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0011 events1 affected294 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Aortic arteriosclerosis	Vascular disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Asthenia	General disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
COVID-19	Infections and infestations	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Cardiac failure	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Cellulitis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Chest discomfort	General disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Cystitis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Diabetic neuropathy	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Erysipelas	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Gastritis	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Haematoma	Vascular disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Influenza	Infections and infestations	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Pneumonia	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Procedural complication	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Renal colic	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk
Renal cyst	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Renal failure	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Retinopathy hypertensive	Eye disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Sepsis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0001 events1 affected293 at risk EG0010 events0 affected294 at risk
Urosepsis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 events0 affected293 at risk EG0011 events1 affected294 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases