Trial Outcomes & Findings for A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3) (NCT NCT04795531)
NCT ID: NCT04795531
Last Updated: 2024-12-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
588 participants
Primary outcome timeframe
Baseline (Week 0), Week 26
Results posted on
2024-12-04
Participant Flow
The trial was conducted at 89 sites in 11 countries as follows (number of sites that screened participants/ number of sites that randomised participants): Argentina (4/4), Austria (3/3), Brazil (4/4), Canada (14/13), China mainland (13/13), Czech Republic (6/6), Denmark (4/4), France (9/8), Mexico (2/2), Taiwan (5/5), United States (28/27).
After randomisation participants continued their pre-trial non-insulin anti-diabetic background medication throughout the entire trial except for sulfonylureas and glinides, which had to be reduced at randomisation by approximately 50% at the discretion of the investigator.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
294
|
294
|
|
Overall Study
Full Analysis Set (FAS)
|
294
|
294
|
|
Overall Study
Safety Analysis Set (SAS)
|
293
|
294
|
|
Overall Study
Treated
|
293
|
294
|
|
Overall Study
COMPLETED
|
288
|
286
|
|
Overall Study
NOT COMPLETED
|
6
|
8
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
2
|
|
Overall Study
Death
|
2
|
1
|
Baseline Characteristics
A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3)
Baseline characteristics by cohort
| Measure |
Insulin Icodec
n=294 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
Total
n=588 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.70 Years
STANDARD_DEVIATION 10.19 • n=5 Participants
|
58.56 Years
STANDARD_DEVIATION 9.74 • n=7 Participants
|
58.13 Years
STANDARD_DEVIATION 9.97 • n=5 Participants
|
|
Sex: Female, Male
Female
|
109 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
219 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
185 Participants
n=5 Participants
|
184 Participants
n=7 Participants
|
369 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
76 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
164 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
203 Participants
n=5 Participants
|
190 Participants
n=7 Participants
|
393 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
80 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
179 Participants
n=5 Participants
|
175 Participants
n=7 Participants
|
354 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 0), Week 26Population: Full analysis set (FAS) included all randomised participants.
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.
Outcome measures
| Measure |
Insulin Icodec
n=294 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Change in Glycated Haemoglobin (HbA1c)
|
-1.57 Percentage of HbA1c
Standard Error 0.05
|
-1.36 Percentage of HbA1c
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 26Population: Full analysis set (FAS) included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Insulin Icodec
n=284 Participants
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.
|
Insulin Degludec
n=290 Participants
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.
|
|---|---|---|
|
Change in Fasting Plasma Glucose (FPG)
|
-3.01 millimoles per liter (mmol/L)
Standard Error 0.11
|
-2.99 millimoles per liter (mmol/L)
Standard Error 0.11
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 31Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Number of Severe Hypoglycaemic Episodes (Level 3)
|
0 Episodes
|
2 Episodes
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 31Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (< 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose [BG] Meter)
|
53 Episodes
|
23 Episodes
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 31Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
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)
|
53 Episodes
|
25 Episodes
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 26Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Number of Severe Hypoglycaemic Episodes (Level 3)
|
0 Episodes
|
0 Episodes
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 26Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)
|
50 Episodes
|
17 Episodes
|
SECONDARY outcome
Timeframe: From baseline (week 0) to week 26Population: Safety analysis set (SAS) included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
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.
Outcome measures
| Measure |
Insulin Icodec
n=293 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
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)
|
50 Episodes
|
17 Episodes
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 26Population: Full analysis set included all randomised participants.
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.
Outcome measures
| Measure |
Insulin Icodec
n=294 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Change in Body Weight
|
2.77 Kilograms (kg)
Standard Error 0.22
|
2.32 Kilograms (kg)
Standard Error 0.24
|
SECONDARY outcome
Timeframe: From week 24 to week 26Population: Full analysis set included all randomised participants.
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.
Outcome measures
| Measure |
Insulin Icodec
n=294 Participants
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.
|
Insulin Degludec
n=294 Participants
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.
|
|---|---|---|
|
Mean Weekly Insulin Dose
|
204.28 Units (U) of insulin
Interval 189.44 to 220.29
|
186.52 Units (U) of insulin
Interval 173.06 to 201.02
|
Adverse Events
Insulin Icodec
Serious events: 15 serious events
Other events: 52 other events
Deaths: 2 deaths
Insulin Degludec
Serious events: 15 serious events
Other events: 29 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Insulin Icodec
n=293 participants at risk
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.
|
Insulin Degludec
n=294 participants at risk
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Vascular disorders
Aortic arteriosclerosis
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
General disorders
Asthenia
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
COVID-19
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Cardiac disorders
Cardiac failure
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
General disorders
Chest discomfort
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Cystitis
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Escherichia bacteraemia
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Vascular disorders
Haematoma
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Influenza
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Injury, poisoning and procedural complications
Procedural complication
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Renal and urinary disorders
Renal cyst
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Renal and urinary disorders
Renal failure
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Eye disorders
Retinopathy hypertensive
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Sepsis
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.34%
1/293 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.00%
0/294 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/293 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
0.34%
1/294 • Number of events 1 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
Other adverse events
| Measure |
Insulin Icodec
n=293 participants at risk
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.
|
Insulin Degludec
n=294 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
COVID-19
|
8.2%
24/293 • Number of events 24 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
4.8%
14/294 • Number of events 14 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Eye disorders
Diabetic retinopathy
|
5.1%
15/293 • Number of events 16 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
2.0%
6/294 • Number of events 7 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
|
Infections and infestations
Influenza
|
5.1%
15/293 • Number of events 18 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
3.1%
9/294 • Number of events 9 • From baseline (Week 0) to Week 31
All presented adverse events (AEs) are treatment emergent. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the trial period (week 31). Results are based on the safety analysis set (SAS) which included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER