DUALTM IX: A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT02773368
Collaborator
(none)
420
88
2
17
4.8
0.3
Study Details
Study Description
Brief Summary
This trial is conducted globally. The aim of this trial is comparing glycaemic control and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) as add-on therapy to SGLT2i (sodium-glucose cotransporter 2 inhibitors) in subjects with type 2 diabetes mellitus.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
420 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus. DUALTM IX - Add-on to SGLT2i
Actual Study Start Date
:
May 23, 2016
Actual Primary Completion Date
:
Sep 26, 2017
Actual Study Completion Date
:
Oct 23, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IDegLira
|
Drug: insulin degludec/liraglutide
IDegLira will be given subcutaneously ( s.c., under the skin) once daily.
|
| Active Comparator: IGlar
|
Drug: insulin glargine
IGlar will be given subcutaneously ( s.c., under the skin) once daily.
|
Outcome Measures
Primary Outcome Measures
- Change in HbA1c (Glycosylated Haemoglobin) [Week 0, Week 26]
The mean change from baseline (week 0) in HbA1c values evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
Secondary Outcome Measures
- Change in Body Weight [Week 0, Week 26]
The mean change from baseline (week 0) in body weight evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Number of Treatment-emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes [Week 0-26]
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe (subjects who were not able to self-treat) and/or BG confirmed by a plasma glucose values <3.1 mmol/L (56 mg/dL) with accompanied symptoms consistent with hypoglycaemia.
- Insulin Dose, Total Daily Dose (U) [After 26 weeks]
Actual daily total insulin dose (Units) was evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Change in Fasting Plasma Glucose (FPG) [Week 0, Week 26]
Change from baseline (week 0) in FPG was evaluated after 26 weeks of randomised treatment.
- Number of Treatment-emergent Adverse Events [Week 0-26]
Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 26. TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
- Responder (Yes/No) for HbA1c Below 7.0% [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets <7.0% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Weight Gain [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets <7.0% without weight gain after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Weight Gain [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% without weight gain after 26 weeks of randomised treatment. The results are based on retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain [After 26 weeks]
The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product.
- Change From Baseline After 26 Weeks in Waist Circumference [After 26 weeks]
Mean change from baseline in waist circumference after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: Cholesterol [After 26 weeks]
The values of total cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein Cholesterol (LDL Cholesterol) [After 26 weeks]
The values of LDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein Cholesterol (HDL Cholesterol) [After 26 weeks]
The values of HDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: Very-low-density Lipoprotein Cholesterol (VLDL Cholesterol) [After 26 weeks]
The values of VLDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: Triglycerides [After 26 weeks]
The values of triglycerides from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in Fasting Lipid Profile: Free Fatty Acids [After 26 weeks]
The values of free fatty acids from fasting lipid profile after 26 weeks of randomised treatment.
- Change From Baseline in the 9-point Self-measured Plasma Glucose (SMPG) Profile [After 26 weeks]
Change in 9-point SMPG profile was evaluated after 26 weeks of randomised treatment. SMPG measurements at baseline and week 26 are presented here at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day.
- Change From Baseline in Self-measured Plasma Glucose (SMPG) 9-point Profile: Mean of the 9-point Profile [After 26 weeks]
Change in mean of the 9-point profile SMPG was evaluated after 26 weeks of randomised treatment. 9-point profile SMPG was measured at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day.
- Change From Baseline in SMPG 9-point Profile: Prandial Plasma Glucose Increments (From Before Meal to 90 Min After Breakfast, Lunch and Dinner). The Mean Increment Over All Meals Will be Derived as the Mean of All Available Meal Increments [After 26 weeks]
Mean prandial plasma glucose increments for each meal (from before meal to 90 min after breakfast, lunch and dinner) was evaluated after 26 weeks of randomised treatment. The mean increment over all meals was derived as the mean of all available meal increments are presented here.
- Change From Baseline in Systolic Blood Pressure [After 26 weeks]
Change from baseline (week 0) in systolic blood pressure (BP) was evaluated after 26 weeks of randomised treatment.
- Change From Baseline in Diastolic Blood Pressure [After 26 weeks]
Change from baseline (week 0) in diastolic blood pressure was evaluated after 26 weeks of randomised treatment.
- Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks [Week 0-26]
Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes (00:01-05:59 - inclusive) during 26 weeks of randomised treatment.
- Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition During 26 Weeks [Week 0-26]
American Diabetes Association (ADA) classification of hypoglycaemic episodes: 1)Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. 2) Documented symptomatic: PG ≤3.9 mmol/L with symptoms. 3) Asymptomatic: PG ≤3.9 mmol/L without symptoms. 4) Probable symptomatic: No measurement with symptoms. 5) Pseudo: PG >3.9 mmol/L with symptoms. 6) Unclassifiable.
- Change From Baseline in Clinical Evaluation After 26 Weeks: Electrocardiogram (ECG) [After 26 weeks]
Reported results are ECG findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing.
- Change From Baseline in Clinical Evaluation After 26 Weeks: Eye Examination: Fundoscopy/Fundus Photography [After 26 weeks]
Reported results are fundus photography/fundoscopy (for both left and right eye) findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing.
- Change From Baseline in Clinical Evaluation After 26 Weeks: Pulse Rate [After 26 weeks]
Change from baseline (week 0) in pulse rate was evaluated after 26 weeks of randomised treatment.
- Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Medical Outcomes Study 36-item Short Form (SF-36v2) [After 26 weeks]
The Short Form (SF)-36v2™ patient reported outcomes (PRO) questionnaire was used to assess the subject's overall health related quality of life (HRQoL). PRO questionnaire (SF-36v2™) measured the HRQoL which contains 36 items covering 8 domains of physical and mental health status. The raw scale scores from the SF-36 were transformed to a 0-100 scale scores (where higher scores indicated a better health status) which is further converted to norm-based scores using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 2009 reference population . The total/overall (SF-36v2™) scores for physical and mental health from baseline to week 26 are presented here.
- Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Treatment Related Impact Measure for Diabetes (TRIM-D) [After 26 weeks]
The patient reported outcomes are calculated based on TRIM-D questionnaire. The TRIM-D questionnaire consists of 5 sub-domains (treatment burden, daily life, diabetes management, compliance and psychological health), where each question is scored to a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D domain scores and the total scores are later transformed to a 0-100 scale for analysis. Summary scores from baseline and week 26 for total/overall scores are presented here.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent - Subjects diagnosed (clinically) with type 2 diabetes mellitus - HbA1c 7.0-11.0% [53-97 mmol/mol] (both inclusive) by central laboratory analysis - Body mass index (BMI) equal to or above 20 kg/m2 and below 40 kg/m2 - Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as well as prior insulin treatment for gestational diabetes - A stable daily dose for at least 90 days prior to the day of screening of any SGLT2i in monotherapy or in combination with metformin ± DPP4i ± pioglitazone. Use of pioglitazone is not allowed in subjects treated with dapagliflozin Exclusion Criteria: - Receipt of any investigational medicinal product within 90 days prior to screening - Use of any OADs (other than SGLT2i in monotherapy or in combination with metformin or DPP4i or pioglitazone as described in the inclusion criteria) within 90 days prior to the day of screening - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., exenatide or liraglutide) within 90 days prior to the day of screening - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g., diabetes ketoacidosis) in the previous 90 days prior to the day of the screening - Subjects presently classified as being in NYHA (New York Heart Association) Class III or IV1 - Renal impairment estimated Glomerular Filtration Rate 60 mL/min/1.73 m2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Impaired liver function, defined as ALT (alanine aminotransferase) equal to or above 2.5 times upper normal limit at screening - Known or suspected hypersensitivity to trial product(s) or related products
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Glendale | Arizona | United States | 85308 |
| 2 | Novo Nordisk Investigational Site | La Jolla | California | United States | 92037 |
| 3 | Novo Nordisk Investigational Site | Mission Viejo | California | United States | 92691 |
| 4 | Novo Nordisk Investigational Site | Northridge | California | United States | 91325 |
| 5 | Novo Nordisk Investigational Site | Palm Springs | California | United States | 92262 |
| 6 | Novo Nordisk Investigational Site | San Ramon | California | United States | 94583 |
| 7 | Novo Nordisk Investigational Site | Boynton Beach | Florida | United States | 33472 |
| 8 | Novo Nordisk Investigational Site | Chiefland | Florida | United States | 32626 |
| 9 | Novo Nordisk Investigational Site | Skokie | Illinois | United States | 60077 |
| 10 | Novo Nordisk Investigational Site | Avon | Indiana | United States | 46123 |
| 11 | Novo Nordisk Investigational Site | Rockville | Maryland | United States | 20852 |
| 12 | Novo Nordisk Investigational Site | Las Vegas | Nevada | United States | 89118 |
| 13 | Novo Nordisk Investigational Site | Teaneck | New Jersey | United States | 07666 |
| 14 | Novo Nordisk Investigational Site | Albany | New York | United States | 12206 |
| 15 | Novo Nordisk Investigational Site | West Seneca | New York | United States | 14224 |
| 16 | Novo Nordisk Investigational Site | Whiteville | North Carolina | United States | 28472 |
| 17 | Novo Nordisk Investigational Site | Mason | Ohio | United States | 45040-6815 |
| 18 | Novo Nordisk Investigational Site | Greer | South Carolina | United States | 29651 |
| 19 | Novo Nordisk Investigational Site | Bristol | Tennessee | United States | 37620-7352 |
| 20 | Novo Nordisk Investigational Site | Austin | Texas | United States | 78731 |
| 21 | Novo Nordisk Investigational Site | Houston | Texas | United States | 77081 |
| 22 | Novo Nordisk Investigational Site | Longview | Texas | United States | 75605 |
| 23 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78228-3419 |
| 24 | Novo Nordisk Investigational Site | Kenosha | Wisconsin | United States | 53144 |
| 25 | Novo Nordisk Investigational Site | Buenos Aires | Argentina | C1425AGC | |
| 26 | Novo Nordisk Investigational Site | Caba | Argentina | C1120AAC | |
| 27 | Novo Nordisk Investigational Site | Caba | Argentina | C1180AAX | |
| 28 | Novo Nordisk Investigational Site | Mendoza | Argentina | 5500 | |
| 29 | Novo Nordisk Investigational Site | Winnipeg | Manitoba | Canada | R2V 4W3 |
| 30 | Novo Nordisk Investigational Site | Moncton | New Brunswick | Canada | E1G 1A7 |
| 31 | Novo Nordisk Investigational Site | Burlington | Ontario | Canada | L7M 4Y1 |
| 32 | Novo Nordisk Investigational Site | London | Ontario | Canada | N6G 2M1 |
| 33 | Novo Nordisk Investigational Site | Smiths Falls | Ontario | Canada | K7A 4W8 |
| 34 | Novo Nordisk Investigational Site | Montreal | Quebec | Canada | H4A 3T2 |
| 35 | Novo Nordisk Investigational Site | Helsinki | Finland | 00100 | |
| 36 | Novo Nordisk Investigational Site | Lahti | Finland | 15110 | |
| 37 | Novo Nordisk Investigational Site | Oulu | Finland | FI-90220 | |
| 38 | Novo Nordisk Investigational Site | Rovaniemi | Finland | 96400 | |
| 39 | Novo Nordisk Investigational Site | Tampere | Finland | 33520 | |
| 40 | Novo Nordisk Investigational Site | Turku | Finland | 20520 | |
| 41 | Novo Nordisk Investigational Site | Budapest | Hungary | 1042 | |
| 42 | Novo Nordisk Investigational Site | Debrecen | Hungary | 4043 | |
| 43 | Novo Nordisk Investigational Site | Komarom | Hungary | 2900 | |
| 44 | Novo Nordisk Investigational Site | Salgótarján | Hungary | 3100 | |
| 45 | Novo Nordisk Investigational Site | Szekszárd | Hungary | 7100 | |
| 46 | Novo Nordisk Investigational Site | Zalaegerszeg | Hungary | 8900 | |
| 47 | Novo Nordisk Investigational Site | Hyderbad | Andhra Pradesh | India | 500 012 |
| 48 | Novo Nordisk Investigational Site | Bhopal | Madhya Pradesh | India | 462037 |
| 49 | Novo Nordisk Investigational Site | Pune | Maharashtra | India | 411040 |
| 50 | Novo Nordisk Investigational Site | Ludhiana | Punjab | India | 141001 |
| 51 | Novo Nordisk Investigational Site | Jaipur | Rajasthan | India | 302004 |
| 52 | Novo Nordisk Investigational Site | Chennai | Tamil Nadu | India | 600029 |
| 53 | Novo Nordisk Investigational Site | Chennai | Tamil Nadu | India | 600086 |
| 54 | Novo Nordisk Investigational Site | Varanasi | Uttar Pradesh | India | 221105 |
| 55 | Novo Nordisk Investigational Site | Kolkata | West Bengal | India | 700054 |
| 56 | Novo Nordisk Investigational Site | New Delhi | India | 110001 | |
| 57 | Novo Nordisk Investigational Site | Barnaul | Russian Federation | 656043 | |
| 58 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 123423 | |
| 59 | Novo Nordisk Investigational Site | Novosibirsk | Russian Federation | 630047 | |
| 60 | Novo Nordisk Investigational Site | Saint-Petersburg | Russian Federation | 191119 | |
| 61 | Novo Nordisk Investigational Site | Saint-Petersburg | Russian Federation | 194358 | |
| 62 | Novo Nordisk Investigational Site | Saint-Petesburg | Russian Federation | 195257 | |
| 63 | Novo Nordisk Investigational Site | St. Petersburg | Russian Federation | 194354 | |
| 64 | Novo Nordisk Investigational Site | Kosice | Slovakia | 040 01 | |
| 65 | Novo Nordisk Investigational Site | Lucenec | Slovakia | 984 01 | |
| 66 | Novo Nordisk Investigational Site | Nitra | Slovakia | 94901 | |
| 67 | Novo Nordisk Investigational Site | Presov | Slovakia | 080 01 | |
| 68 | Novo Nordisk Investigational Site | Trnava | Slovakia | 91701 | |
| 69 | Novo Nordisk Investigational Site | Celje | Slovenia | SI-3000 | |
| 70 | Novo Nordisk Investigational Site | Koper | Slovenia | SI-6000 | |
| 71 | Novo Nordisk Investigational Site | Kranj | Slovenia | 4000 | |
| 72 | Novo Nordisk Investigational Site | Murska Sobota | Slovenia | SI-9000 | |
| 73 | Novo Nordisk Investigational Site | Trbovlje | Slovenia | 1420 | |
| 74 | Novo Nordisk Investigational Site | Almería | Spain | 04001 | |
| 75 | Novo Nordisk Investigational Site | Antequera | Spain | 29200 | |
| 76 | Novo Nordisk Investigational Site | Barcelona | Spain | 08035 | |
| 77 | Novo Nordisk Investigational Site | Boadilla del Monte | Spain | 28660 | |
| 78 | Novo Nordisk Investigational Site | Sevilla | Spain | 41003 | |
| 79 | Novo Nordisk Investigational Site | Sevilla | Spain | 41009 | |
| 80 | Novo Nordisk Investigational Site | Villamartin | Spain | 11650 | |
| 81 | Novo Nordisk Investigational Site | Baden | Switzerland | 5400 | |
| 82 | Novo Nordisk Investigational Site | Genève 14 | Switzerland | 1211 | |
| 83 | Novo Nordisk Investigational Site | Luzern 16 | Switzerland | 6000 | |
| 84 | Novo Nordisk Investigational Site | Olten | Switzerland | 4600 | |
| 85 | Novo Nordisk Investigational Site | Schaffhausen | Switzerland | 8208 | |
| 86 | Novo Nordisk Investigational Site | Winterthur | Switzerland | 8400 | |
| 87 | Novo Nordisk Investigational Site | Zollikerberg | Switzerland | 8125 | |
| 88 | Novo Nordisk Investigational Site | Zürich | Switzerland | 8091 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02773368
Other Study ID Numbers:
- NN9068-4229
- 2015-001596-48
- U1111-1168-9343
- REec-2016-2248
First Posted:
May 16, 2016
Last Update Posted:
Aug 11, 2020
Last Verified:
Aug 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at 74 sites in 11 countries as follows: Argentina (3), Canada (5), Finland (6), Hungary (5), India (8), Russian Federation (7), Slovakia (5), Slovenia (4), Spain (6), Switzerland (5) and United States (20). |
|---|---|
| Pre-assignment Detail | Subjects with type 2 diabetes mellitus on oral anti-diabetic drug (OAD) therapy with stable daily dose of sodium glucose co-transporter 2 inhibitors (SGLT2i) either as monotherapy or in combination with metformin ± dipeptidyl peptidase-4 inhibitors (DPP4i) ± pioglitazone according to locally approved label for at least 90 days prior to screening. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Period Title: Overall Study | ||
| STARTED | 210 | 210 |
| Exposed | 209 | 210 |
| COMPLETED | 200 | 206 |
| NOT COMPLETED | 10 | 4 |
Baseline Characteristics
| Arm/Group Title | IDegLira | IGlar | Total |
|---|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Total of all reporting groups |
| Overall Participants | 210 | 210 | 420 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
56.1
(10.4)
|
57.2
(10.2)
|
56.7
(10.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
89
42.4%
|
84
40%
|
173
41.2%
|
| Male |
121
57.6%
|
126
60%
|
247
58.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
31
14.8%
|
37
17.6%
|
68
16.2%
|
| Not Hispanic or Latino |
179
85.2%
|
173
82.4%
|
352
83.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
0.5%
|
1
0.2%
|
| Asian |
31
14.8%
|
35
16.7%
|
66
15.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
1.4%
|
2
1%
|
5
1.2%
|
| White |
175
83.3%
|
171
81.4%
|
346
82.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
0.5%
|
1
0.5%
|
2
0.5%
|
Outcome Measures
| Title | Change in HbA1c (Glycosylated Haemoglobin) |
|---|---|
| Description | The mean change from baseline (week 0) in HbA1c values evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | Week 0, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| HbA1c (%) at baseline |
8.20
(0.93)
|
8.36
(1.08)
|
| HbA1c (%) change from baseline to week 26 |
-1.94
(0.95)
|
-1.68
(1.05)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IDegLira, IGlar |
|---|---|---|
| Comments | Analysis was based on ANCOVA model with treatment, pre-trial OAD, region as factors and baseline HbA1c as covariate. Data obtained after premature treatment discontinuation are included in the analysis. Missing data was imputed using unconditional reference based multiple imputation including data obtained after premature treatment discontinuation. The non-inferiority margin of 0.3 % was added to the end-of-treatment value for prematurely discontinued and withdrawn from trial IDegLira subjects. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority of IDegLira was considered confirmed if the upper limit of the two-sided 95% confidence interval (CI) for mean treatment difference (IDegLira minus IGlar) was strictly below 0.3%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Contrast |
| Estimated Value | -0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.48 to -0.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | IDegLira minus IGlar | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | IDegLira, IGlar |
|---|---|---|
| Comments | This endpoint was analysed using an ANCOVA model with treatment, pre-trial OAD and region as factors and corresponding baseline value as covariate. Data obtained after premature treatment discontinuation were included in the analysis. Missing data were imputed using unconditional reference based multiple imputation including data obtained after premature treatment discontinuation. | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority of IDegLira was considered confirmed if the test procedure was not stopped (i.e. non-inferiority of IDegLira was confirmed for change from baseline in HbA1c; and superiority of IDegLira was confirmed for weight change and the number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes) and if the upper limit of the two-sided 95% CI for the mean treatment difference (IDegLira minus IGlar) in change from baseline in HbA1c was strictly below 0%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Contrast |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 95% -0.50 to -0.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | IDegLira minus IGlar | |
| Title | Change in Body Weight |
|---|---|
| Description | The mean change from baseline (week 0) in body weight evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | Week 0, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Body weight (kg) at baseline |
89.3
(17.6)
|
87.2
(17.2)
|
| Body weight (kg) change from baseline to week 26 |
-0.0
(3.8)
|
2.0
(3.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IDegLira, IGlar |
|---|---|---|
| Comments | This endpoint was analysed using an ANCOVA model with treatment, pre-trial OAD and region as factors and corresponding baseline weight as covariate. Data obtained after premature treatment discontinuation were included in the analysis. Missing data were imputed using unconditional reference based multiple imputation including data obtained after premature treatment discontinuation. | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority of IDegLira was considered confirmed if the test procedure was not stopped (i.e. non-inferiority of IDegLira was confirmed for change from baseline in HbA1c) and if the upper limit of the two-sided 95% CI for the mean treatment difference (IDegLira minus IGlar) in change from baseline in body weight was strictly below 0 kg. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Contrast |
| Estimated Value | -1.92 | |
| Confidence Interval |
(2-Sided) 95% -2.64 to -1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | IDegLira minus IGlar | |
| Title | Number of Treatment-emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes |
|---|---|
| Description | Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe (subjects who were not able to self-treat) and/or BG confirmed by a plasma glucose values <3.1 mmol/L (56 mg/dL) with accompanied symptoms consistent with hypoglycaemia. |
| Time Frame | Week 0-26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Number [Number of episodes] |
38
|
95
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IDegLira, IGlar |
|---|---|---|
| Comments | This endpoint was analysed using a negative binomial regression model with a log link and the logarithm of the exposure time as offset. The model included treatment and pre-trial OAD as fixed factors. Missing data were imputed using multiple imputations (conditioning on expected event rate before premature treatment discontinuation or withdrawal from trial as if treated with IGlar). | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority of IDegLira was considered confirmed if the test procedure was not stopped (i.e. non-inferiority of IDegLira was confirmed for change from baseline in HbA1c and superiority of IDegLira was confirmed for change from baseline in body weight) and if the upper limit of the two-sided 95% CI for the rate ratio (IDegLira over IGlar) of rate of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes was strictly below 1. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Ratio |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 0.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | IDegLira over IGlar | |
| Title | Insulin Dose, Total Daily Dose (U) |
|---|---|
| Description | Actual daily total insulin dose (Units) was evaluated after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Mean (Standard Deviation) [Units (U)] |
36.2
(13.4)
|
53.5
(26.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IDegLira, IGlar |
|---|---|---|
| Comments | The endpoint was analysed using an ANCOVA model with treatment, pre-trial OAD and region as factors and corresponding baseline HbA1c as covariate. Missing data were imputed using unconditional reference based multiple imputation including data obtained after premature treatment discontinuation. | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority of IDegLira was considered confirmed if the test procedure was not stopped (i.e. non-inferiority of IDegLira was confirmed for change from baseline in HbA1c; and superiority of IDegLira was confirmed for weight change, number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes and change in HbA1c) and if the upper limit of the two-sided 95% CI for the mean treatment difference (IDegLira minus IGlar) in insulin dose after 26 weeks was strictly below 0 U. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Contrast |
| Estimated Value | -15.37 | |
| Confidence Interval |
(2-Sided) 95% -19.60 to -11.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | IDegLira minus IGlar | |
| Title | Change in Fasting Plasma Glucose (FPG) |
|---|---|
| Description | Change from baseline (week 0) in FPG was evaluated after 26 weeks of randomised treatment. |
| Time Frame | Week 0, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| FPG (mmol/L) at baseline |
9.51
(2.69)
|
9.57
(2.40)
|
| FPG (mmol/L) change from baseline to week 26 |
-3.72
(2.89)
|
-3.50
(2.43)
|
| Title | Number of Treatment-emergent Adverse Events |
|---|---|
| Description | Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 26. TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. |
| Time Frame | Week 0-26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Number [Number of events] |
450
|
386
|
| Title | Responder (Yes/No) for HbA1c Below 7.0% |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets <7.0% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
167
79.5%
|
144
68.6%
|
| No |
30
14.3%
|
58
27.6%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Weight Gain |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets <7.0% without weight gain after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
91
43.3%
|
38
18.1%
|
| No |
106
50.5%
|
164
78.1%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
156
74.3%
|
114
54.3%
|
| No |
41
19.5%
|
88
41.9%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
83
39.5%
|
34
16.2%
|
| No |
114
54.3%
|
168
80%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% after 26 weeks of randomised treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
147
70%
|
100
47.6%
|
| No |
50
23.8%
|
102
48.6%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Weight Gain |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5% without weight gain after 26 weeks of randomised treatment. The results are based on retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
84
40%
|
26
12.4%
|
| No |
113
53.8%
|
176
83.8%
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
137
|
79
|
| No |
60
|
123
|
| Title | Responder After 26 Weeks (Yes/No) for: HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment and Without Weight Gain |
|---|---|
| Description | The proportion of subjects achieving pre-defined HbA1c targets ≤ 6.5%without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment and without weight gain. The results presented included retrieved data at week 26 for subjects who prematurely discontinued the trial product. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Yes |
77
|
24
|
| No |
120
|
178
|
| Title | Change From Baseline After 26 Weeks in Waist Circumference |
|---|---|
| Description | Mean change from baseline in waist circumference after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Waist circum. (cm) at baseline |
105.9
(12.7)
|
104.7
(11.3)
|
| Waist circum. (cm) change from baseline to week 26 |
-0.6
(4.6)
|
0.7
(3.9)
|
| Title | Change From Baseline in Fasting Lipid Profile: Cholesterol |
|---|---|
| Description | The values of total cholesterol from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Total cholesterol (mmol/L) at baseline |
4.42
|
4.45
|
| Total cholesterol (mmol/L) at week 26 |
4.27
|
4.27
|
| Title | Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein Cholesterol (LDL Cholesterol) |
|---|---|
| Description | The values of LDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| LDL cholesterol (mmol/L) at baseline |
2.28
|
2.28
|
| LDL cholesterol (mmol/L) at week 26 |
2.20
|
2.31
|
| Title | Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein Cholesterol (HDL Cholesterol) |
|---|---|
| Description | The values of HDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| HDL cholesterol (mmol/L) at baseline |
1.14
|
1.14
|
| HDL cholesterol (mmol/L) at week 26 |
1.17
|
1.17
|
| Title | Change From Baseline in Fasting Lipid Profile: Very-low-density Lipoprotein Cholesterol (VLDL Cholesterol) |
|---|---|
| Description | The values of VLDL cholesterol from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| VLDL cholesterol (mmol/L) at baseline |
0.75
|
0.80
|
| VLDL cholesterol (mmol/L) at week 26 |
0.70
|
0.67
|
| Title | Change From Baseline in Fasting Lipid Profile: Triglycerides |
|---|---|
| Description | The values of triglycerides from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Triglycerides (mmol/L) at baseline |
1.67
|
1.73
|
| Triglycerides (mmol/L) at week 26 |
1.55
|
1.47
|
| Title | Change From Baseline in Fasting Lipid Profile: Free Fatty Acids |
|---|---|
| Description | The values of free fatty acids from fasting lipid profile after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Free fatty acids (mmol/L) at baseline |
0.58
|
0.61
|
| Free fatty acids (mmol/L) at week 26 |
0.38
|
0.42
|
| Title | Change From Baseline in the 9-point Self-measured Plasma Glucose (SMPG) Profile |
|---|---|
| Description | Change in 9-point SMPG profile was evaluated after 26 weeks of randomised treatment. SMPG measurements at baseline and week 26 are presented here at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline and week 26 for mentioned time points. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Before breakfast - Baseline |
9.01
(2.18)
|
9.00
(1.91)
|
| Ninety (90) minutes after breakfast - Baseline |
11.79
(3.09)
|
11.77
(2.99)
|
| Before lunch - Baseline |
8.93
(2.80)
|
9.20
(2.95)
|
| Ninety (90) minutes after lunch - Baseline |
11.24
(3.26)
|
11.22
(3.06)
|
| Before dinner - Baseline |
9.33
(2.70)
|
9.36
(2.89)
|
| Ninety (90) minutes after dinner - Baseline |
11.40
(3.04)
|
11.40
(2.99)
|
| At bedtime - Baseline |
10.38
(3.16)
|
10.71
(3.13)
|
| At 4.00 AM - Baseline |
8.80
(2.41)
|
9.00
(2.50)
|
| Before breakfast the following day - Baseline |
8.60
(2.02)
|
8.81
(1.92)
|
| Before breakfast - Week 26 |
5.40
(1.24)
|
5.39
(1.21)
|
| Ninety (90) minutes after breakfast - Week 26 |
7.20
(1.86)
|
8.35
(2.40)
|
| Before lunch - Week 26 |
5.83
(1.36)
|
6.35
(1.88)
|
| Ninety (90) minutes after lunch - Week 26 |
7.25
(1.73)
|
8.49
(2.28)
|
| Before dinner - Week 26: |
6.43
(1.61)
|
6.77
(2.03)
|
| Ninety (90) minutes after dinner - Week 26 |
7.85
(1.95)
|
8.70
(2.19)
|
| At bedtime - Week 26 |
7.05
(1.91)
|
7.79
(2.20)
|
| At 4.00 AM - Week 26 |
5.58
(1.17)
|
5.72
(1.51)
|
| Before breakfast the following day - Week 26 |
5.23
(1.09)
|
5.36
(1.38)
|
| Title | Change From Baseline in Self-measured Plasma Glucose (SMPG) 9-point Profile: Mean of the 9-point Profile |
|---|---|
| Description | Change in mean of the 9-point profile SMPG was evaluated after 26 weeks of randomised treatment. 9-point profile SMPG was measured at the following mentioned time points:1) Before breakfast, 2) 90 mins after the start of Breakfast, 3) Before lunch, 4) 90 mins after the start of lunch, 5) Before dinner, 6) 90 mins after the start of dinner, 7) At bedtime, 8) At 4 AM, 9) Before breakfast the following day. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Mean 9-point SMPG (mmol/L) at baseline |
9.98
(2.17)
|
10.06
(2.04)
|
| Mean 9-point SMPG change from baseline to week 26 |
-3.47
(2.01)
|
-2.98
(1.91)
|
| Title | Change From Baseline in SMPG 9-point Profile: Prandial Plasma Glucose Increments (From Before Meal to 90 Min After Breakfast, Lunch and Dinner). The Mean Increment Over All Meals Will be Derived as the Mean of All Available Meal Increments |
|---|---|
| Description | Mean prandial plasma glucose increments for each meal (from before meal to 90 min after breakfast, lunch and dinner) was evaluated after 26 weeks of randomised treatment. The mean increment over all meals was derived as the mean of all available meal increments are presented here. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Baseline |
2.38
(1.73)
|
2.28
(1.88)
|
| Change from baseline to week 26 |
-0.86
(1.95)
|
-0.09
(1.96)
|
| Title | Change From Baseline in Systolic Blood Pressure |
|---|---|
| Description | Change from baseline (week 0) in systolic blood pressure (BP) was evaluated after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Systolic BP (mmHg) at baseline |
130.5
(14.3)
|
128.9
(13.1)
|
| Systolic BP (mmHg) change from baseline to week 26 |
-3.0
(12.7)
|
0.6
(12.0)
|
| Title | Change From Baseline in Diastolic Blood Pressure |
|---|---|
| Description | Change from baseline (week 0) in diastolic blood pressure was evaluated after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Diastolic (mmHg) at baseline |
79.4
(8.0)
|
78.9
(8.9)
|
| Diastolic (mmHg) change from baseline to week 26 |
-1.2
(8.4)
|
-1.1
(8.3)
|
| Title | Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks |
|---|---|
| Description | Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes (00:01-05:59 - inclusive) during 26 weeks of randomised treatment. |
| Time Frame | Week 0-26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Number [Number of episodes] |
6
|
13
|
| Title | Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition During 26 Weeks |
|---|---|
| Description | American Diabetes Association (ADA) classification of hypoglycaemic episodes: 1)Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. 2) Documented symptomatic: PG ≤3.9 mmol/L with symptoms. 3) Asymptomatic: PG ≤3.9 mmol/L without symptoms. 4) Probable symptomatic: No measurement with symptoms. 5) Pseudo: PG >3.9 mmol/L with symptoms. 6) Unclassifiable. |
| Time Frame | Week 0-26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Severe - ADA |
1
|
0
|
| Documented symptomatic - ADA |
239
|
419
|
| Asymptomatic - ADA |
850
|
902
|
| Probably symptomatic - ADA |
23
|
5
|
| Pseudo - ADA |
10
|
14
|
| Unclassifiable hypoglycaemia - ADA |
2
|
0
|
| Title | Change From Baseline in Clinical Evaluation After 26 Weeks: Electrocardiogram (ECG) |
|---|---|
| Description | Reported results are ECG findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". Number analysed = Number of subjects contributed to the analysis at screening and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Screening, Normal |
142
|
141
|
| Screening, Abnormal NCS |
66
|
69
|
| Screening, Abnormal CS |
1
|
0
|
| Screening, Missing |
0
|
0
|
| Week 26, Normal |
134
|
136
|
| Week 26, Abnormal NCS |
58
|
64
|
| Week 26, Abnormal CS |
2
|
0
|
| Week 26, Missing |
0
|
0
|
| Title | Change From Baseline in Clinical Evaluation After 26 Weeks: Eye Examination: Fundoscopy/Fundus Photography |
|---|---|
| Description | Reported results are fundus photography/fundoscopy (for both left and right eye) findings at screening and week 26 of randomised treatment. Since the values measured at the baseline (week 0) were not collected, the screening data (week -2, which is <= 2 weeks before baseline) is presented here. The findings are categorised as: 1) Normal. 2) Abnormal (not clinically significant [NCS]). 3) Abnormal (clinically significant [CS]). 4) Missing. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". Number analysed = Number of subjects contributed to the analysis at screening and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Screening, Left eye (Normal) |
134
|
131
|
| Screening, Left eye (Abnormal -NCS) |
68
|
74
|
| Screening, Left eye (Abnormal-CS) |
7
|
4
|
| Screening, Left eye (Missing) |
0
|
0
|
| Week 26, Left eye (Normal) |
123
|
125
|
| Week 26, Left eye (Abnormal -NCS) |
66
|
68
|
| Week 26, Left eye (Abnormal-CS) |
2
|
4
|
| Week 26, Left eye (Missing) |
0
|
0
|
| Screening, Right eye (Normal) |
133
|
133
|
| Screening, Right eye (Abnormal-NCS) |
69
|
72
|
| Screening, Right eye (Abnormal- CS) |
7
|
4
|
| Screening, Right eye (Missing) |
0
|
0
|
| Week 26, Right eye (Normal) |
120
|
127
|
| Week 26, Right eye (Abnormal-NCS) |
69
|
66
|
| Week 26, Right eye (Abnormal- CS) |
2
|
4
|
| Week 26, Right eye (Missing) |
0
|
0
|
| Title | Change From Baseline in Clinical Evaluation After 26 Weeks: Pulse Rate |
|---|---|
| Description | Change from baseline (week 0) in pulse rate was evaluated after 26 weeks of randomised treatment. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects who received at least one dose of the investigational product or comparator. Subjects in the safety set contributed to the evaluation "as treated". Number analysed = Number of subjects contributed to the analysis at baseline (week 0) and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 209 | 210 |
| Pulse (beats/min) at baseline |
76.1
(9.1)
|
75.0
(9.5)
|
| Pulse (beats/min) change from baseline to week 26 |
2.0
(8.4)
|
-0.4
(8.2)
|
| Title | Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Medical Outcomes Study 36-item Short Form (SF-36v2) |
|---|---|
| Description | The Short Form (SF)-36v2™ patient reported outcomes (PRO) questionnaire was used to assess the subject's overall health related quality of life (HRQoL). PRO questionnaire (SF-36v2™) measured the HRQoL which contains 36 items covering 8 domains of physical and mental health status. The raw scale scores from the SF-36 were transformed to a 0-100 scale scores (where higher scores indicated a better health status) which is further converted to norm-based scores using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 2009 reference population . The total/overall (SF-36v2™) scores for physical and mental health from baseline to week 26 are presented here. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline and week 26 for overall physical and mental scores. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| Overall physical - Baseline |
51.3
|
51.5
|
| Overall physical - Week 26 |
53.2
|
54.6
|
| Overall mental - Baseline |
53.3
|
53.3
|
| Overall mental - Week 26 |
54.4
|
54.4
|
| Title | Change From Baseline in Patient Reported Outcomes (PROs) After 26 Weeks: Summary Scores of Treatment Related Impact Measure for Diabetes (TRIM-D) |
|---|---|
| Description | The patient reported outcomes are calculated based on TRIM-D questionnaire. The TRIM-D questionnaire consists of 5 sub-domains (treatment burden, daily life, diabetes management, compliance and psychological health), where each question is scored to a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D domain scores and the total scores are later transformed to a 0-100 scale for analysis. Summary scores from baseline and week 26 for total/overall scores are presented here. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomised subjects. The statistical evaluation of the FAS followed the intent-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Number analysed = Number of subjects contributed to the analysis at baseline and week 26. |
| Arm/Group Title | IDegLira | IGlar |
|---|---|---|
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. |
| Measure Participants | 210 | 210 |
| TRIM-D scores at baseline |
75.9
|
75.9
|
| TRIM-D scores at week 26 |
84.4
|
83.9
|
Adverse Events
| Time Frame | Adverse events (AEs) were collected from first day (week 0) of exposure to randomised treatment of 26 weeks + 30 days follow-up visits after the last dose on trial product. All reported AEs are treatment emergent (i.e., TEAE). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Results are based on the safety analysis set, which included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated". | |||
| Arm/Group Title | IDegLira | IGlar | ||
| Arm/Group Description | Subjects were administered with insulin degludec/liraglutide (IDegLira: 100 U/3.6 mg per mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IDegLira was supplied in a 3 mL prefilled PDS290 pen-injector with a fixed IDeg/liraglutide ratio of 100 U/3.6 mg per mL solution. IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg /0.36 mg liraglutide) and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values that were measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). The maximum daily dose was 50 dose steps (50 U IDeg /1.8 mg Lira). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | Subjects were administered with insulin glargine (IGlar: 100 U/mL) subcutaneously (s.c.) once daily for a duration of 26 weeks. IGlar was supplied in a 3 mL pre-filled Solostar® pen at 100 U/mL solution. IGlar treatment was initiated with the starting dose of 10 U and adjusted twice weekly on fixed days. Dose adjustment was based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values measured on the days of the titration and two days prior to the titration (target SMPG: 4.0-5.0 mmol/L [72 - 90 mg/dL]). Pre-trial OAD treatments were continued according to current local label. The randomised subjects would be on either SGLT2i monotherapy or SGLT2i ± metformin ± pioglitazone, this treatment was to be unchanged throughout the trial, unless there was a safety concern. | ||
All Cause Mortality |
||||
| IDegLira | IGlar | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/209 (0%) | 0/210 (0%) | ||
Serious Adverse Events |
||||
| IDegLira | IGlar | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/209 (2.9%) | 7/210 (3.3%) | ||
| Cardiac disorders | ||||
| Cardiac failure chronic | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Coronary artery disease | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Myocardial infarction | 1/209 (0.5%) | 1 | 0/210 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Infections and infestations | ||||
| Infected skin ulcer | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Pneumonia | 2/209 (1%) | 2 | 1/210 (0.5%) | 1 |
| Urinary tract infection | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Investigations | ||||
| Blood potassium increased | 1/209 (0.5%) | 1 | 0/210 (0%) | 0 |
| Cardiovascular evaluation | 1/209 (0.5%) | 1 | 0/210 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Gastrointestinal stromal tumour | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Nervous system disorders | ||||
| Haemorrhagic stroke | 1/209 (0.5%) | 1 | 0/210 (0%) | 0 |
| Product Issues | ||||
| Device failure | 1/209 (0.5%) | 2 | 0/210 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
| Chronic kidney disease | 0/209 (0%) | 0 | 1/210 (0.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| IDegLira | IGlar | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 49/209 (23.4%) | 45/210 (21.4%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 12/209 (5.7%) | 22 | 1/210 (0.5%) | 2 |
| Infections and infestations | ||||
| Viral upper respiratory tract infection | 16/209 (7.7%) | 22 | 22/210 (10.5%) | 24 |
| Investigations | ||||
| Lipase increased | 12/209 (5.7%) | 15 | 3/210 (1.4%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 11/209 (5.3%) | 12 | 9/210 (4.3%) | 15 |
| Nervous system disorders | ||||
| Headache | 18/209 (8.6%) | 35 | 19/210 (9%) | 27 |
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".
Results Point of Contact
| Name/Title | Clinical Reporting Anchor and Disclosure (1452) |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | (+1) 866-867-7178 |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02773368
Other Study ID Numbers:
- NN9068-4229
- 2015-001596-48
- U1111-1168-9343
- REec-2016-2248
First Posted:
May 16, 2016
Last Update Posted:
Aug 11, 2020
Last Verified:
Aug 1, 2020