Trial Outcomes & Findings for 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 (NCT NCT03951805)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

205 participants

Primary outcome timeframe

During the last 2 weeks of treatment (week 15 and 16)

Results posted on

2021-04-05

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	Insulin 287 (Titration Algorithm A) 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.	Insulin 287 (Titration Algorithm B) 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	Insulin 287 (Titration Algorithm C) 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.	Insulin Glargine (Titration Algorithm D) 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 Study STARTED	51	51	52	51
Overall Study Full Analysis Set (FAS)	51	51	52	51
Overall Study Safety Analysis Set (SAS)	51	51	52	51
Overall Study COMPLETED	50	51	52	51
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin 287 (Titration Algorithm A) 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.	Insulin 287 (Titration Algorithm B) 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	Insulin 287 (Titration Algorithm C) 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.	Insulin Glargine (Titration Algorithm D) 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 Study Adverse Event	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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 n=205 Participants Total of all reporting groups
Age, Continuous	59.8 years STANDARD_DEVIATION 9.1 • n=5 Participants	61.2 years STANDARD_DEVIATION 8.0 • n=7 Participants	61.4 years STANDARD_DEVIATION 8.0 • n=5 Participants	60.2 years STANDARD_DEVIATION 8.1 • n=4 Participants	60.7 years STANDARD_DEVIATION 8.3 • n=21 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	24 Participants n=4 Participants	95 Participants n=21 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	27 Participants n=4 Participants	110 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants	46 Participants n=7 Participants	50 Participants n=5 Participants	48 Participants n=4 Participants	193 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized White	51 participants n=5 Participants	49 participants n=7 Participants	51 participants n=5 Participants	47 participants n=4 Participants	198 participants n=21 Participants
Race/Ethnicity, Customized other	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: During the last 2 weeks of treatment (week 15 and 16)

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = Number of participants who contributed to the analysis.

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.

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=51 Participants 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.	Insulin Glargine (Titration Algorithm D) n=50 Participants 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.
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)	76.65 Percentage of time Standard Error 1.81	82.97 Percentage of time Standard Error 1.80	80.89 Percentage of time Standard Error 1.81	75.89 Percentage of time Standard Error 1.82

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Full analysis set included all randomised participants.

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).

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
Change in HbA1c (Glycated Haemoglobin)	-1.00 Percentage point of HbA1c Standard Error 0.08	-1.22 Percentage point of HbA1c Standard Error 0.08	-1.38 Percentage point of HbA1c Standard Error 0.08	-1.02 Percentage point of HbA1c Standard Error 0.08

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = Number of participants who contributed to the analysis.

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).

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=50 Participants 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	Insulin 287 (Titration Algorithm C) n=51 Participants 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.	Insulin Glargine (Titration Algorithm D) n=49 Participants 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.
Change in Fasting Plasma Glucose (FPG)	-2.23 Millimoles per liter (mmol/L) Standard Error 0.17	-2.42 Millimoles per liter (mmol/L) Standard Error 0.17	-3.01 Millimoles per liter (mmol/L) Standard Error 0.17	-2.34 Millimoles per liter (mmol/L) Standard Error 0.17

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Full analysis set included all randomised participants.

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).

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
Change in Body Weight	0.87 Kilogram (Kg) Standard Error 0.35	1.11 Kilogram (Kg) Standard Error 0.35	1.25 Kilogram (Kg) Standard Error 0.35	0.63 Kilogram (Kg) Standard Error 0.35

SECONDARY outcome

Timeframe: During the last 2 weeks of treatment (week 15 and 16)

Population: Full analysis set included all randomised participants.

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).

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
Weekly Insulin Dose	142.47 Units of insulin (U) Interval 119.78 to 169.45	176.38 Units of insulin (U) Interval 148.3 to 209.78	208.90 Units of insulin (U) Interval 175.94 to 248.04	145.56 Units of insulin (U) Interval 122.38 to 173.12

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 21 (visit 20)

Population: Safety analysis set included all participants exposed to at least one dose of trial product.

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.

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
Number of Treatment Emergent Adverse Events (TEAEs)	44 Count of events	67 Count of events	58 Count of events	45 Count of events

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Safety analysis set included all participants exposed to at least one dose of trial product.

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.

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
Number of Severe Hypoglycaemic Episodes (Level 3)	0 Count of events	0 Count of events	0 Count of events	0 Count of events

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Safety analysis set included all participants exposed to at least one dose of trial product.

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.

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
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)	1 Count of events	2 Count of events	8 Count of events	0 Count of events

SECONDARY outcome

Timeframe: From baseline week 0 (visit 2) to week 16 (visit 18)

Population: Safety analysis set included all participants exposed to at least one dose of trial product.

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.

Outcome measures

Outcome measures
Measure	Insulin 287 (Titration Algorithm A) n=51 Participants 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.	Insulin 287 (Titration Algorithm B) n=51 Participants 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	Insulin 287 (Titration Algorithm C) n=52 Participants 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.	Insulin Glargine (Titration Algorithm D) n=51 Participants 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.
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)	14 Count of events	20 Count of events	110 Count of events	10 Count of events

Adverse Events

Insulin 287 (Titration Algorithm A)

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Insulin 287 (Titration Algorithm B)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Insulin 287 (Titration Algorithm C)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Insulin Glargine (Titration Algorithm D)

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Insulin 287 (Titration Algorithm A) n=51 participants at risk 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.	Insulin 287 (Titration Algorithm B) n=51 participants at risk 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	Insulin 287 (Titration Algorithm C) n=52 participants at risk 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.	Insulin Glargine (Titration Algorithm D) n=51 participants at risk 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.
Cardiac disorders Angina pectoris	2.0% 1/51 • Number of events 1 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	0.00% 0/51 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Choroid neoplasm	2.0% 1/51 • Number of events 1 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	0.00% 0/51 • 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. 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.
Infections and infestations Erysipelas	0.00% 0/51 • 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. 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.	2.0% 1/51 • Number of events 1 • 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. 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.	0.00% 0/52 • 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. 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.	0.00% 0/51 • 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. 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.
Surgical and medical procedures Knee arthroplasty	0.00% 0/51 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	2.0% 1/51 • Number of events 1 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	2.0% 1/51 • Number of events 1 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	0.00% 0/51 • 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. 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.
Infections and infestations Pneumonia	0.00% 0/51 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	2.0% 1/51 • Number of events 1 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	2.0% 1/51 • Number of events 1 • 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. 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.	0.00% 0/51 • 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. 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.	0.00% 0/52 • 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. 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.	0.00% 0/51 • 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. 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.

Other adverse events

Other adverse events
Measure	Insulin 287 (Titration Algorithm A) n=51 participants at risk 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.	Insulin 287 (Titration Algorithm B) n=51 participants at risk 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	Insulin 287 (Titration Algorithm C) n=52 participants at risk 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.	Insulin Glargine (Titration Algorithm D) n=51 participants at risk 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.
Musculoskeletal and connective tissue disorders Back pain	9.8% 5/51 • Number of events 5 • 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. 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.	3.9% 2/51 • Number of events 3 • 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. 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.	1.9% 1/52 • Number of events 1 • 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. 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.	2.0% 1/51 • Number of events 1 • 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. 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.
Nervous system disorders Headache	0.00% 0/51 • 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. 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.	5.9% 3/51 • Number of events 3 • 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. 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.	9.6% 5/52 • Number of events 7 • 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. 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.	3.9% 2/51 • Number of events 3 • 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. 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.
Infections and infestations Nasopharyngitis	9.8% 5/51 • Number of events 7 • 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. 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.	13.7% 7/51 • Number of events 7 • 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. 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.	3.8% 2/52 • Number of events 2 • 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. 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.	11.8% 6/51 • Number of events 6 • 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. 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.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

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