Trial Outcomes & Findings for A Trial Comparing Sequential Addition of Insulin Aspart Versus Further Dose Increase With Insulin Degludec/Liraglutide in Subjects With Type 2 Diabetes Mellitus, Previously Treated With Insulin Degludec/Liraglutide and Metformin and in Need of Further Intensification (NCT NCT02100475)

NCT ID: NCT02100475

Last Updated: 2017-01-20

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

31 participants

Primary outcome timeframe

Week 0, week 26

Results posted on

2017-01-20

Participant Flow

The trial was conducted at 19 sites in 8 countries as follows: Argentina: 2 sites; Greece: 2 sites, Hungary: 1 site; Russian Federation: 5 sites; Slovakia: 4 sites, South Africa: 1 site; Spain: 1 site, United States: 3 sites.

Subjects with type 2 diabetes mellitus who were inadequately controlled (HbA1c level ≥ 7% \[53 mmol/mol\]) on treatment with IDegLira and metformin after 26 weeks of treatment in the NN9068-3952 trial were screened. Eligible subjects were randomised in a 1:1 manner to one of the two parallel treatment groups (IDegLira or IDegLira + IAsp).

Participant milestones

Participant milestones
Measure	IDegLira Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Overall Study STARTED	16	15
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	IDegLira Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Overall Study Unclassified	1	2
Overall Study Withdrawal criteria	1	0

Baseline Characteristics

A Trial Comparing Sequential Addition of Insulin Aspart Versus Further Dose Increase With Insulin Degludec/Liraglutide in Subjects With Type 2 Diabetes Mellitus, Previously Treated With Insulin Degludec/Liraglutide and Metformin and in Need of Further Intensification

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDegLira n=16 Participants Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp n=15 Participants IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	Total n=31 Participants Total of all reporting groups
Age, Continuous	57.3 Years STANDARD_DEVIATION 11.7 • n=5 Participants	57.4 Years STANDARD_DEVIATION 11.2 • n=7 Participants	57.4 Years STANDARD_DEVIATION 11.3 • n=5 Participants
Gender Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Gender Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
HbA1c	7.6 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	7.7 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 • n=7 Participants	7.6 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: Full analysis set (FAS) included all randomised subjects (31 subjects). Missing data were imputed using the last observation carried forward (LOCF) method.

Change from baseline in HbA1c after 26 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDegLira n=16 Participants Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp n=15 Participants IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	-0.43 Percentage of glycosylated haemoglobin Standard Deviation 0.94	-0.14 Percentage of glycosylated haemoglobin Standard Deviation 1.09

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised subject (31 subjects). Missing data were imputed using the LOCF method.

Change from baseline in body weight after 26 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDegLira n=16 Participants Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp n=15 Participants IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Change From Baseline in Body Weight	0.9 Kilograms Standard Deviation 2.1	1.5 Kilograms Standard Deviation 3.2

SECONDARY outcome

Timeframe: Week 0 - 26

Population: Safety analysis set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (31 subjects). Confirmed hypoglycaemic episodes were reported by 2 subjects in IDegLira arm and 2 subjects in IDegLira + IAsp arm.

Treatment-emergent hypoglycaemic episodes: if the onset of the episode occurred on or after the first day of investigational medicinal product administration, and no later than 7 days after the last day on investigational medicinal product. Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded plasma glucose \< 3.1 mmol/L (56 mg/dL).

Outcome measures

Outcome measures
Measure	IDegLira n=16 Participants Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp n=15 Participants IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Number of Treatment-emergent Confirmed Hypoglycaemic Episodes	34 Number of episodes	4 Number of episodes

Adverse Events

IDegLira

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

IDegLira + IAsp

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IDegLira n=16 participants at risk Insulin degludec/liraglutide (IDegLira) was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. Intensification with IDegLira was performed by dose optimisation up to a maximum of 80 dose steps (80 units IDeg/2.9 mg Lira). All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).	IDegLira + IAsp n=15 participants at risk IDegLira was given subcutaneously (s.c., under the skin) once daily in combination with metformin. The starting dose of IDegLira was the dose of IDegLira used at the end of the NN9068-3952 trial. IDegLira was titrated up to a maximum dose of 50 dose steps (50 units IDeg/1.8 mg Lira) with sequential add-on of bolus insulin aspart (IAsp). Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured daily. All subjects continued with metformin at pre-trial doses (≥ 1500 mg or the maximum tolerated dose).
Cardiac disorders Acute coronary syndrome	6.2% 1/16 • Number of events 1 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.	0.00% 0/15 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/16 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.	6.7% 1/15 • Number of events 1 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.
Surgical and medical procedures Coronary revascularisation	6.2% 1/16 • Number of events 1 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.	0.00% 0/15 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.
Renal and urinary disorders Renal failure	0.00% 0/16 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.	6.7% 1/15 • Number of events 1 • From first trial-related activity (week 0) after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27). SAS included all subjects receiving at least one dose of the investigational product or comparator, (SAS = 31 subjects). A treatment-emergent adverse event (TEAE) was defined as an event that had an onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment.

Other adverse events

Additional Information

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