A Research Study in People With Type 2 Diabetes to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03922750
• Collaborator: (none)
• Enrollment: 154
• Locations: 38
• Arms: 3
• Actual Duration (Months): 8.6
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study compares insulin 287 (a possible new medicine) to insulin glargine (a medicine doctors can already prescribe) in people with type 2 diabetes. Different ways of switching from the insulin which the participants are already on to insulin 287 are also compared. This is done to find the best way to switch to insulin 287. The participants will either get insulin 287 that they will have to inject once a week or insulin glargine that they will have to inject once a day. Which treatment any participant gets is decided by chance. The study will last for about 5 months (23 weeks). The participants will have 14 clinic visits and 6 phone calls with the study doctor. At 3 of the clinic visits participants will be asked not to eat or drink anything (except for water) in the last 8 hours before the visit. During the study, the doctor will ask the participants to: 1) measure their blood sugar every day with a blood sugar meter using a finger prick; 2) write down different information in a diary daily and return this to their study doctor. 3) wear a medical device (sensor) that measures the participants blood sugar all the time for 18 weeks (about 4 months) during the study.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Insulin icodec; Drug: Insulin glargine U100	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing NNC0148-0287 C (Insulin 287) Versus Insulin Glargine U100, Both in Combination With Metformin, With or Without DPP4 Inhibitors and With or Without SGLT2 Inhibitors, in Basal Insulin Treated Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: May 9, 2019
• Actual Primary Completion Date: Dec 19, 2019
• Actual Study Completion Date: Jan 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin 287 (with 100% loading dose) Participants will receive insulin 287 injections once weekly (OW). A unit to unit switch approach with an additional 100% loading dose of insulin 287 will be used.	Drug: Insulin icodec; Participants will receive subcutaneous (s.c.) injections of Insulin 287 OW for 16 weeks.; Other Names: Insulin 287
Experimental: Insulin 287 (without loading dose) Participants will receive insulin 287 injections OW. A unit to unit switch approach without loading dose of insulin 287 will be used.	Drug: Insulin icodec; Participants will receive subcutaneous (s.c.) injections of Insulin 287 OW for 16 weeks.; Other Names: Insulin 287
Active Comparator: Insulin glargine U100 Participants will receive insulin glargine U100 once daily (OD).	Drug: Insulin glargine U100; Participants will receive s.c. injections of insulin glargine OD for 16 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring) [During the last 2 weeks of treatment (week 15 and 16)]

   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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Secondary Outcome Measures

1. Change in Glycosylated Haemoglobin (HbA1c) [From baseline week 0 (V2) to week 16 (V18)]

   Estimated mean change from baseline (week 0) in HbA1c at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

2. Change in Fasting Plasma Glucose (FPG) [From baseline week 0 (V2) to week 16 (V18)]

   Estimated mean change from baseline (week 0) in FPG at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

3. Change in Body Weight [From baseline week 0 (V2) to week 16 (V18)]

   Estimated mean change from baseline (week 0) in body weight at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

4. Weekly Insulin Dose [During the last 2 weeks of treatment (week 15 and 16)]

   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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

5. Number of Treatment-emergent Adverse Events (TEAEs) [From baseline week 0 (V2) to week 21 (V20)]

   An adverse event(AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage.. 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 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. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product.

6. Number of Severe Hypoglycaemic Episodes (Level 3) [From baseline week 0 (V2) to week 16 (V18)]

   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 during weeks 0-16 are presented.

7. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) [From baseline week 0 (V2) to week 16 (V18)]

   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 <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 during weeks 0-16 are presented.

8. 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 BG Meter) [From baseline week 0 (V2) to week 16 (V18)]

   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. Number of hypoglycaemic alert episodes (level 1) (equal to or above 3.0 and below 3.9 mmol/L (equal to or above 54 and below 70 mg/dL), confirmed by BG meter) that occured during weeks 0-16 are presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.

• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening.

• Glycosylated haemoglobin (HbA1c) of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory.

• Treated with once daily or twice daily basal insulin analogue (insulin degludec, insulin detemir, insulin glargine U100 or U300, total daily dose of 10-50 U, both inclusive) greater than or equal to 90 days prior to the day of screening.

• Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s):

1. Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical records).

2. Free or fixed combination therapy: Metformin as outlined above with or without dipeptidyl peptidase 4 inhibitors (DPP4i) with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i) is allowed: 1) DPP4i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose); 2) SGLT2i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose.

• Body mass index (BMI) less than or equal to 40.0 kg/m^2.

Exclusion criteria:

• Known or suspected hypersensitivity to trial product(s) or related products.

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method.

• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days before screening.

• Any disorder, except for conditions associated with type 2 diabetes mellitus, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.

• Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation.

• Known hypoglycaemic unawareness as indicated by the Investigator according to Clarke's questionnaire question 8.

• Recurrent severe hypoglycaemic episodes within the last year as judged by the Investigator.

• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
2	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
3	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
4	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
5	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
6	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
7	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
8	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37203
9	Novo Nordisk Investigational Site	Dallas	Texas	United States	75226
10	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
11	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
12	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
13	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
14	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6G 2E1
15	Novo Nordisk Investigational Site	Surrey	British Columbia	Canada	V3Z 2N6
16	Novo Nordisk Investigational Site	Vancouver	British Columbia	Canada	V5Y 3W2
17	Novo Nordisk Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
18	Novo Nordisk Investigational Site	Brampton	Ontario	Canada	L6S 0C6
19	Novo Nordisk Investigational Site	Concord	Ontario	Canada	L4K 4M2
20	Novo Nordisk Investigational Site	Etobicoke	Ontario	Canada	M9R 4E1
21	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8M 1K7
22	Novo Nordisk Investigational Site	Markham	Ontario	Canada	L3P 7P2
23	Novo Nordisk Investigational Site	Sarnia	Ontario	Canada	N7T 4X3
24	Novo Nordisk Investigational Site	Broumov		Czechia	550 01
25	Novo Nordisk Investigational Site	Holešov		Czechia	76901
26	Novo Nordisk Investigational Site	Hranice		Czechia	75301
27	Novo Nordisk Investigational Site	Trutnov		Czechia	541 01
28	Novo Nordisk Investigational Site	Falkensee		Germany	14612
29	Novo Nordisk Investigational Site	Hamburg		Germany	22607
30	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
31	Novo Nordisk Investigational Site	Münster		Germany	48145
32	Novo Nordisk Investigational Site	Oldenburg I. Holst		Germany	23758
33	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
34	Novo Nordisk Investigational Site	Bergamo		Italy	24127
35	Novo Nordisk Investigational Site	Catanzaro		Italy	88100
36	Novo Nordisk Investigational Site	Milano		Italy	20122
37	Novo Nordisk Investigational Site	Milano		Italy	20132
38	Novo Nordisk Investigational Site	Roma		Italy	00161

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - May 28, 2020
• Statistical Analysis Plan - May 28, 2020

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03922750
• Other Study ID Numbers: NN1436-4466; U1111-1219-5541; 2018-003407-18
• First Posted: Apr 22, 2019
• Last Update Posted: Jan 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Recruitment Details

The trial was conducted at 34 sites in 5 countries as follows: Canada (10), Italy (5), Czech Republic (4), Germany (5) and the United States (10). In addition, 3 sites in the United states and 1 site in Germany screened, but didn't randomise any subjects.

Pre-assignment Detail

Participants were randomised to receive once weekly insulin 287 using any of 2 different switch approaches or once daily insulin glargine; as an add-on to background therapy with basal insulin analogue with metformin, with or without dipeptidyl peptidase-4 inhibitors (DPP4i) and with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i) at stable, pre-trial dose and at same frequency during the entire treatment period unless due to safety concerns related to the background medication.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Period Title: Overall Study
STARTED	50	54	50
Full Analysis Set (FAS)	50	54	50
Safety Analysis Set (SAS)	50	54	50
COMPLETED	50	53	49
NOT COMPLETED	0	1	1

Baseline Characteristics

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100	Total
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Total of all reporting groups
Overall Participants	50	54	50	154
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (8.2)	62.4 (7.2)	60.5 (7.9)	61.7 (7.8)
Sex: Female, Male (Count of Participants)
Female	11 22%	15 27.8%	17 34%	43 27.9%
Male	39 78%	39 72.2%	33 66%	111 72.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2%	6 11.1%	6 12%	13 8.4%
Not Hispanic or Latino	49 98%	48 88.9%	44 88%	141 91.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	9 18%	4 7.4%	3 6%	16 10.4%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.9%	0 0%	1 0.6%
Black or African American	2 4%	3 5.6%	3 6%	8 5.2%
White	39 78%	46 85.2%	44 88%	129 83.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)
Description	The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame	During the last 2 weeks of treatment (week 15 and 16)

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	49	53	50
Least Squares Mean (Standard Error) [Percentage of time]	65.99 (2.34)	72.86 (2.13)	64.98 (2.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin 287 (Without Loading Dose), Insulin Glargine U100
	Comments	The response and change from baseline in response during last two weeks of treatment (week 15 and 16) were analysed using an analysis of covariance (ANCOVA) model with treatment, pre-trial insulin treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values were imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset was analysed separately and estimates were combined using Rubin's rules.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7542
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; -5.33 to 7.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin 287 (With 100% Loading Dose), Insulin Glargine U100
	Comments	The response and change from baseline in response during last two weeks of treatment (week 15 and 16) were analysed using an analysis of covariance (ANCOVA) model with treatment, pre-trial insulin treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values were imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset was analysed separately and estimates were combined using Rubin's rules.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	7.88
	Confidence Interval	(2-Sided) 95%; 1.83 to 13.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c)
Description	Estimated mean change from baseline (week 0) in HbA1c at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Least Squares Mean (Standard Error) [Percentage point of HbA1c]	-0.47 (0.09)	-0.77 (0.09)	-0.54 (0.09)

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Description	Estimated mean change from baseline (week 0) in FPG at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. Overall number analyzed = participants with available data.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	52	49
Least Squares Mean (Standard Error) [Millimoles per liter (mmol/L)]	-0.83 (0.23)	-0.69 (0.22)	-0.57 (0.23)

4. Secondary Outcome

Title	Change in Body Weight
Description	Estimated mean change from baseline (week 0) in body weight at week 16 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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. Overall number analyzed = participants with available data.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Least Squares Mean (Standard Error) [Kilogram (Kg)]	1.32 (0.36)	0.61 (0.34)	0.10 (0.35)

5. Secondary Outcome

Title	Weekly Insulin Dose
Description	Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Time Frame	During the last 2 weeks of treatment (week 15 and 16)

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. Overall Number analyzed = participants with available data.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Least Squares Mean (95% Confidence Interval) [Units of insulin (U)]	242.31	191.03	195.91

6. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event(AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage.. 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 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. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product.
Time Frame	From baseline week 0 (V2) to week 21 (V20)

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all participants exposed to at least one dose of trial product.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Number [Count of events]	77	85	76

7. Secondary Outcome

Title	Number of Severe Hypoglycaemic Episodes (Level 3)
Description	Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred during weeks 0-16 are presented.
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

SAS included all participants exposed to at least one dose of trial product.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Number [Count of events]	0	0	0

8. Secondary Outcome

Title	Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
Description	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of <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 during weeks 0-16 are presented.
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

SAS included all participants exposed to at least one dose of trial product.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Number [Count of events]	3	17	16

9. Secondary Outcome

Title	Number of Hypoglycaemic Alert Episodes(Level 1) (Greater Than or Equal to 3.0 and Below 3.9 mmol/L (Greater Than or Equal to 54 and Below 70 mg/dL), Confirmed by BG Meter)
Description	Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Number of hypoglycaemic alert episodes (level 1) (equal to or above 3.0 and below 3.9 mmol/L (equal to or above 54 and below 70 mg/dL), confirmed by BG meter) that occured during weeks 0-16 are presented.
Time Frame	From baseline week 0 (V2) to week 16 (V18)

Outcome Measure Data

Analysis Population Description

SAS included all participants exposed to at least one dose of trial product.

Arm/Group Title	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
Measure Participants	50	54	50
Number [Count of events]	79	78	71

Adverse Events

Time Frame	Weeks 0-21.
Adverse Event Reporting Description	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 TEAEs. TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period.
Arm/Group Title	Insulin 287 (Without Loading Dose)		Insulin 287 (With 100% Loading Dose)		Insulin Glargine U100
Arm/Group Description	Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.		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 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.		Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.
All Cause Mortality
	Insulin 287 (Without Loading Dose)		Insulin 287 (With 100% Loading Dose)		Insulin Glargine U100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/54 (0%)		0/50 (0%)
Serious Adverse Events
	Insulin 287 (Without Loading Dose)		Insulin 287 (With 100% Loading Dose)		Insulin Glargine U100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		2/54 (3.7%)		1/50 (2%)
Cardiac disorders
Acute myocardial infarction	0/50 (0%)	0	1/54 (1.9%)	1	0/50 (0%)	0
Myocardial infarction	0/50 (0%)	0	0/54 (0%)	0	1/50 (2%)	1
Infections and infestations
Muscle abscess	0/50 (0%)	0	1/54 (1.9%)	1	0/50 (0%)	0
Injury, poisoning and procedural complications
Facial bones fracture	0/50 (0%)	0	1/54 (1.9%)	2	0/50 (0%)	0
Fall	0/50 (0%)	0	1/54 (1.9%)	1	0/50 (0%)	0
Joint injury	0/50 (0%)	0	1/54 (1.9%)	1	0/50 (0%)	0
Upper limb fracture	0/50 (0%)	0	1/54 (1.9%)	1	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin 287 (Without Loading Dose)		Insulin 287 (With 100% Loading Dose)		Insulin Glargine U100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/50 (36%)		20/54 (37%)		18/50 (36%)
Eye disorders
Diabetic retinopathy	2/50 (4%)	2	2/54 (3.7%)	2	3/50 (6%)	3
Gastrointestinal disorders
Constipation	0/50 (0%)	0	1/54 (1.9%)	1	4/50 (8%)	4
Diarrhoea	1/50 (2%)	1	2/54 (3.7%)	2	3/50 (6%)	4
Nausea	1/50 (2%)	1	0/54 (0%)	0	3/50 (6%)	4
General disorders
Instillation site haemorrhage	0/50 (0%)	0	0/54 (0%)	0	4/50 (8%)	7
Medical device site haemorrhage	2/50 (4%)	2	5/54 (9.3%)	7	1/50 (2%)	3
Infections and infestations
Influenza	3/50 (6%)	3	1/54 (1.9%)	1	0/50 (0%)	0
Nasopharyngitis	7/50 (14%)	8	8/54 (14.8%)	9	2/50 (4%)	3
Upper respiratory tract infection	1/50 (2%)	1	2/54 (3.7%)	2	4/50 (8%)	4
Musculoskeletal and connective tissue disorders
Pain in extremity	3/50 (6%)	4	1/54 (1.9%)	1	1/50 (2%)	2
Nervous system disorders
Headache	1/50 (2%)	1	3/54 (5.6%)	3	3/50 (6%)	3
Vascular disorders
Hypertension	3/50 (6%)	3	1/54 (1.9%)	1	1/50 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.