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A Research Study to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine in People With Type 2 Diabetes Who Have Not Used Insulin Before

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ClinicalTrials.gov Identifier: NCT03951805
Recruitment Status : Completed
First Posted : May 15, 2019
Results First Posted : January 8, 2021
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Insulin icodec
Drug: Insulin Glargine
Enrollment 205
Recruitment Details The trial was conducted at 38 sites in 7 countries as follows: Croatia (4), Germany (9), Hungary (3), Poland (4), Slovakia (5), Spain (4), United States (9). In addition, 1 site in Slovakia and 3 sites in the United States screened, but didn't randomise any subjects.
Pre-assignment Details Participants were randomised to receive once weekly insulin 287 using one of 3 different titration algorithms (A, B, C), or once daily insulin glargine (titration algorithm D); as add-on to background therapy with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) and with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i).
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Period Title: Overall Study
Started 51 51 52 51
Full Analysis Set (FAS) 51 51 52 51
Safety Analysis Set (SAS) 51 51 52 51
Completed 50 51 52 51
Not Completed 1 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D) Total
Hide Arm/Group Description Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Total of all reporting groups
Overall Number of Baseline Participants 51 51 52 51 205
Hide Baseline Analysis Population Description
The full analysis set included all randomised participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 51 participants 52 participants 51 participants 205 participants
59.8  (9.1) 61.2  (8.0) 61.4  (8.0) 60.2  (8.1) 60.7  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 52 participants 51 participants 205 participants
Female
24
  47.1%
23
  45.1%
24
  46.2%
24
  47.1%
95
  46.3%
Male
27
  52.9%
28
  54.9%
28
  53.8%
27
  52.9%
110
  53.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 52 participants 51 participants 205 participants
Hispanic or Latino
2
   3.9%
5
   9.8%
2
   3.8%
3
   5.9%
12
   5.9%
Not Hispanic or Latino
49
  96.1%
46
  90.2%
50
  96.2%
48
  94.1%
193
  94.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 52 participants 51 participants 205 participants
American Indian or Alaska Native 0 0 0 1 1
Asian 0 2 0 0 2
Black or African American 0 0 1 1 2
Native Hawaiian or other Pacific Islander 0 0 0 1 1
White 51 49 51 47 198
other 0 0 0 1 1
1.Primary Outcome
Title Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring)
Hide Description The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). The endpoint is based on data recorded by CGM system. It was required that at least 70% of the planned CGM measurements during weeks 15-16 were available for endpoint data to be included in the analysis.
Time Frame During the last 2 weeks of treatment (week 15 and 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomised participants. Overall number of participants analyzed = Number of participants who contributed to the analysis.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 51 50
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of time
76.65  (1.81) 82.97  (1.80) 80.89  (1.81) 75.89  (1.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin 287 (Titration Algorithm A), Insulin Glargine (Titration Algorithm D)
Comments The response and change from baseline in response during the last two weeks of treatment (week 15 and 16) are analysed using an analysis of covariance (ANCOVA) model with treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values are imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset is analysed separately and estimates are combined using Rubin's rules.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7675
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
-4.28 to 5.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin 287 (Titration Algorithm B), Insulin Glargine (Titration Algorithm D)
Comments The response and change from baseline in response during the last two weeks of treatment (week 15 and 16) are analysed using an analysis of covariance (ANCOVA) model with treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values are imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset is analysed separately and estimates are combined using Rubin's rules.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 7.08
Confidence Interval (2-Sided) 95%
2.12 to 12.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Insulin 287 (Titration Algorithm C), Insulin Glargine (Titration Algorithm D)
Comments The response and change from baseline in response during the last two weeks of treatment (week 15 and 16) are analysed using an analysis of covariance (ANCOVA) model with treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values are imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset is analysed separately and estimates are combined using Rubin's rules.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0519
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 5.01
Confidence Interval (2-Sided) 95%
-0.04 to 10.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in HbA1c (Glycated Haemoglobin)
Hide Description Estimated mean change in HbA1c from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomised participants.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Least Squares Mean (Standard Error)
Unit of Measure: Percentage point of HbA1c
-1.00  (0.08) -1.22  (0.08) -1.38  (0.08) -1.02  (0.08)
3.Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG)
Hide Description Estimated mean change in FPG from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomised participants. Overall number of participants analyzed = Number of participants who contributed to the analysis.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 50 51 49
Least Squares Mean (Standard Error)
Unit of Measure: Millimoles per liter (mmol/L)
-2.23  (0.17) -2.42  (0.17) -3.01  (0.17) -2.34  (0.17)
4.Secondary Outcome
Title Change in Body Weight
Hide Description Estimated mean change in body weight from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomised participants.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Least Squares Mean (Standard Error)
Unit of Measure: Kilogram (Kg)
0.87  (0.35) 1.11  (0.35) 1.25  (0.35) 0.63  (0.35)
5.Secondary Outcome
Title Weekly Insulin Dose
Hide Description Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame During the last 2 weeks of treatment (week 15 and 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomised participants.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units of insulin (U)
142.47
(119.78 to 169.45)
176.38
(148.30 to 209.78)
208.90
(175.94 to 248.04)
145.56
(122.38 to 173.12)
6.Secondary Outcome
Title Number of Treatment Emergent Adverse Events (TEAEs)
Hide Description A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The on-treatment observation period was the time period from first dose of trial product (week 0, visit 2) until the follow-up visit (week 21, visit 20) or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin.
Time Frame From baseline week 0 (visit 2) to week 21 (visit 20)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants exposed to at least one dose of trial product.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Measure Type: Number
Unit of Measure: Count of events
44 67 58 45
7.Secondary Outcome
Title Number of Severe Hypoglycaemic Episodes (Level 3)
Hide Description Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants exposed to at least one dose of trial product.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Measure Type: Number
Unit of Measure: Count of events
0 0 0 0
8.Secondary Outcome
Title Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) or Severe Hypoglycaemic Episodes (Level 3)
Hide Description Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occured from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants exposed to at least one dose of trial product.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Measure Type: Number
Unit of Measure: Count of events
1 2 8 0
9.Secondary Outcome
Title Number of Hypoglycaemic Alert Episodes (Level 1) (Greater Than or Equal to 3.0 and Below 3.9 mmol/L (Greater Than or Equal to 54 and Below 70 mg/dL), Confirmed by Blood Glucose (BG) Meter)
Hide Description Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and < 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occured from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.
Time Frame From baseline week 0 (visit 2) to week 16 (visit 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants exposed to at least one dose of trial product.
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description:
Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication
Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
Overall Number of Participants Analyzed 51 51 52 51
Measure Type: Number
Unit of Measure: Count of events
14 20 110 10
Time Frame From baseline (week 0) to week 21 Results are based on the safety analysis set which included all participants exposed to at least one dose of trial product.
Adverse Event Reporting Description All presented adverse events are treatment emergent adverse events (TEAEs). TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The on-treatment observation period was the time period from first dose of trial product until the follow-up visit or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin.
 
Arm/Group Title Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Hide Arm/Group Description Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; > 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication. Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.
All-Cause Mortality
Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)      0/51 (0.00%)      0/52 (0.00%)      0/51 (0.00%)    
Hide Serious Adverse Events
Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/51 (5.88%)      1/51 (1.96%)      0/52 (0.00%)      2/51 (3.92%)    
Cardiac disorders         
Angina pectoris  1  1/51 (1.96%)  1 0/51 (0.00%)  0 0/52 (0.00%)  0 0/51 (0.00%)  0
Infections and infestations         
Erysipelas  1  0/51 (0.00%)  0 1/51 (1.96%)  1 0/52 (0.00%)  0 0/51 (0.00%)  0
Pneumonia  1  0/51 (0.00%)  0 0/51 (0.00%)  0 0/52 (0.00%)  0 1/51 (1.96%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Choroid neoplasm  1  1/51 (1.96%)  1 0/51 (0.00%)  0 0/52 (0.00%)  0 0/51 (0.00%)  0
Metastasis  1  1/51 (1.96%)  1 0/51 (0.00%)  0 0/52 (0.00%)  0 0/51 (0.00%)  0
Transitional cell carcinoma  1  1/51 (1.96%)  1 0/51 (0.00%)  0 0/52 (0.00%)  0 0/51 (0.00%)  0
Surgical and medical procedures         
Knee arthroplasty  1  0/51 (0.00%)  0 0/51 (0.00%)  0 0/52 (0.00%)  0 1/51 (1.96%)  1
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin 287 (Titration Algorithm A) Insulin 287 (Titration Algorithm B) Insulin 287 (Titration Algorithm C) Insulin Glargine (Titration Algorithm D)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/51 (17.65%)      10/51 (19.61%)      7/52 (13.46%)      9/51 (17.65%)    
Infections and infestations         
Nasopharyngitis  1  5/51 (9.80%)  7 7/51 (13.73%)  7 2/52 (3.85%)  2 6/51 (11.76%)  6
Musculoskeletal and connective tissue disorders         
Back pain  1  5/51 (9.80%)  5 2/51 (3.92%)  3 1/52 (1.92%)  1 1/51 (1.96%)  1
Nervous system disorders         
Headache  1  0/51 (0.00%)  0 3/51 (5.88%)  3 5/52 (9.62%)  7 2/51 (3.92%)  3
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Reporting Anchor and Disclosure (1452)
Organization: Novo Nordisk A/S
Phone: (+1) 866-867-7178
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03951805    
Other Study ID Numbers: NN1436-4465
U1111-1219-5474 ( Other Identifier: World Health Organization (WHO) )
2018-003406-11 ( EudraCT Number )
First Submitted: May 10, 2019
First Posted: May 15, 2019
Results First Submitted: December 11, 2020
Results First Posted: January 8, 2021
Last Update Posted: April 5, 2021