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Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as add-on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes (SUSTAIN™ 4)

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ClinicalTrials.gov Identifier: NCT02128932
Recruitment Status : Completed
First Posted : May 1, 2014
Results First Posted : March 8, 2018
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: semaglutide
Drug: insulin glargine
Enrollment 1089
Recruitment Details The trial was conducted at196 sites in 14 countries. Argentina: 3 sites; Croatia: 3 sites; France: 5 sites; Germany: 11 sites; India: 12 sites; Macedonia: 3 sites; Mexico: 3 sites; Netherlands: 3 sites; Romania: 5 sites; Slovakia: 5 sites; Slovenia:3 sites; South Africa: 4 sites; United Kingdom: 13 sites; United States: 123 sites.
Pre-assignment Details Insulin-naïve subjects diagnosed with type 2 diabetes and on stable diabetes treatment with metformin or metformin and SU (metformin ≥1500 mg or maximum tolerated dose and SU≥ half of maximum allowed dose according to national label) for at least 90 days before screening. Stable is defined as unchanged medication and unchanged dose.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Period Title: Overall Study
Started 362 360 360
Completed 335 341 342
Not Completed 27 19 18
Reason Not Completed
Withdrawal by Subject             11             7             8
Death             2             0             2
Lost to Follow-up             2             1             1
No reason for withdrawal             12             11             7
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine Total
Hide Arm/Group Description Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day Total of all reporting groups
Overall Number of Baseline Participants 362 360 360 1082
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
56.5  (10.3) 56.7  (10.4) 56.2  (10.6) 56.5  (10.4)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
18-64 years 278 281 281 840
65-74 years 72 61 67 200
75-84 years 12 18 12 42
>=85 years 0 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
Female
165
  45.6%
178
  49.4%
165
  45.8%
508
  47.0%
Male
197
  54.4%
182
  50.6%
195
  54.2%
574
  53.0%
HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
8.13  (0.85) 8.25  (0.94) 8.13  (0.88) 8.17  (0.89)
Fasting plasma glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
172.4  (50.52) 179.2  (53.74) 174.2  (49.06) 175.3  (51.18)
Body weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
93.73  (21.39) 94.00  (22.48) 92.61  (21.52) 93.45  (21.79)
Diastolic Blood pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
79.67  (8.04) 80.32  (8.32) 79.78  (9.20) 79.72  (8.53)
Systolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 362 participants 360 participants 360 participants 1082 participants
131.57  (14.06) 132.21  (16.05) 132.38  (15.77) 132.06  (15.31)
1.Primary Outcome
Title Change in HbA1c From Baseline
Hide Description Change in HbA1c from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomized semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: percentage
-1.21  (0.05) -1.64  (0.05) -0.83  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide 1.0 mg/Week, Insulin Glargine
Comments The post baseline responses were analysed using a mixed model for repeated measurements with treatment , country and stratum as fixed factors and baseline value as covariate, all nested within visit.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was concluded if the upper limit of the two-sided 95% confidence interval for the estimated treatment difference between semaglutide 1.0 mg and insulin glargine was below the pre-specified non-inferiority margin (0.3 %).
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-0.96 to -0.67
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Semaglutide 0.5mg/Week, Insulin Glargine
Comments The post baseline responses were analysed using a mixed model for repeated meausrements with treatment, country and stratum value as covariate, all nested within visit.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was concluded if the upper limit of the two-sided 95 % confidence interval for the estimated treatment difference between semaglutide 0.5 mg and insulin glargine was below the pre-specified non-inferiority margin (0.3%).
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.52 to -0.24
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Body Weight From Baseline
Hide Description Change in body weight from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: Kg
-3.47  (0.24) -5.17  (0.24) 1.15  (0.23)
3.Secondary Outcome
Title Change in Fasting Plasma Glucose From Baseline
Hide Description Change in fasting plasma glucose from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-36.74  (2.14) -49.21  (2.15) -38.18  (2.03)
4.Secondary Outcome
Title Change in Diastolic Blood Pressure.
Hide Description Change in diastolic blood pressure from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-1.38  (0.43) -0.98  (0.44) -1.44  (0.41)
5.Secondary Outcome
Title Change in Systolic Blood Pressure.
Hide Description Change in systolic blood pressure from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-4.65  (0.72) -5.17  (0.73) -1.68  (0.68)
6.Secondary Outcome
Title Change in Patient Reported Outcome (PRO) Questionnaire, Questionnaire SF-36v2™
Hide 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 on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 U.S. general population. The (SF-36v2™) values displayed are the estimated mean change from baseline to week 30.
Time Frame Week 0, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Bodily pain 0.95  (0.51) 1.76  (0.51) 0.90  (0.48)
General Health 1.95  (0.38) 2.78  (0.38) 1.63  (0.36)
Mental Component summary, MCS 1.23  (0.47) 1.33  (0.47) 0.25  (0.44)
Mental Health 1.69  (0.46) 1.17  (0.47) 0.54  (0.44)
Physical Component summary, PCS 1.18  (0.36) 2.09  (0.36) 1.18  (0.34)
Physical Functioning 1.64  (0.43) 1.49  (0.43) 0.69  (0.41)
Role-emotional 0.88  (0.54) 1.73  (0.54) 0.06  (0.51)
Role-physical 0.90  (0.46) 1.97  (0.46) 0.78  (0.43)
Social functioning 1.13  (0.48) 1.04  (0.48) 0.36  (0.45)
Vitality 1.71  (0.46) 2.09  (0.46) 0.95  (0.44)
7.Secondary Outcome
Title Change in Patient Reported Outcome Questionnaires. (PROs), Diabetes Treatment Satisfaction Questionnaire (DTSQs)
Hide Description The Diabetes Treatment Satisfaction Questionnaire (DTSQs) questionnaire was to be used to assess a subject’s treatment satisfaction. This questionnaire contained 8 components and measured the treatment for diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment. The value presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. The values displayed are the estimated mean change from baseline to week 30.
Time Frame Week 0, week 30
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Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.86  (0.28) 5.37  (0.29) 3.99  (0.27)
8.Secondary Outcome
Title Subjects Who Achieve HbA1c ≤6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE)
Hide Description Subjects who achieve HbA1c ≤6.5% (48 mmol/mol), American Association of Clinical Endocrinologists (AACE) after 30 weeks of treatment
Time Frame After 30 weeks treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide (s.c.) or insulin glargine. Subjects in the FAS contributed to the evaluation based on the treatment assigned at randomisation.
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description:
Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day.
Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
Overall Number of Participants Analyzed 362 360 360
Measure Type: Number
Unit of Measure: Count of participants
Yes 135 195 63
No 227 165 297
Time Frame All adverse events presented here are treatment emergent adverse events (TEAE). A TEAE included events that had onset date (or increase in severity) on or after the first day of exposure (week 0) to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).
Adverse Event Reporting Description A treatment-emergent adverse event (TEAE) was defined as an AE that had onset date (or increased in severity) during the ‘on-treatment’ observation period.
 
Arm/Group Title Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Hide Arm/Group Description Subjects on semaglutide followed a fixed dose-escalation. The maintenance dose of 0.5 mg was to be reached after 4 doses (4 weeks) of 0.25 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects randomised to semaglutide followed a fixed dose-escalation regimen. The maintenance dose of 1.0 mg was to be reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg semaglutide. Doses could not be changed during the trial after the maintenance dose had been reached. One test pen was to be supplied per subject at the screening visit in order to ensure the subject`s willingness and ability to self-inject. The test pen contained semaglutide placebo, solution for injection, 1.5 mL prefilled PDS290 pen-injector and was to be administered once. The PDS290 pen-injector for semaglutide is a prefilled pen integrated with a 1.5 mL cartridge containing semaglutide 1.34 mg/mL and is designed to be used with NovoFine®, NovoFine® Plus and NovoTwist® disposable needles. Once weekly (same day of the week) administered by s.c. injection in thigh, abdomen or upper arm, at any time of the day. Subjects on insulin glargine were to start on 10 IU s.c. injected OD. The insulin dose adjustment had to aim to reach a pre-breakfast FPG of 4.0 to <5.5 mmol/L (71- <100 mg/dL). Once daily solution for injection in a 3 mL pre-filled SoloStar® pen to be administered in the thigh, abdomen or upper arm, at any time of the day
All-Cause Mortality
Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/362 (6.08%)      17/360 (4.72%)      18/360 (5.00%)    
Blood and lymphatic system disorders       
Anaemia  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Cardiac disorders       
Arteriosclerosis coronary artery  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Atrial fibrillation  1  1/362 (0.28%)  1 1/360 (0.28%)  1 1/360 (0.28%)  1
Coronary artery disease  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Coronary artery stenosis  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Ischaemic cardiomyopathy  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Myocarditis  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Ear and labyrinth disorders       
Vertigo  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Eye disorders       
Cataract  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Gastrointestinal disorders       
Anal fissure  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Incarcerated inguinal hernia  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Intestinal obstruction  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Nausea  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Pancreatitis acute  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Vomiting  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
General disorders       
Death  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Systemic inflammatory response syndrome  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Immune system disorders       
Corneal graft rejection  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Infections and infestations       
Atypical pneumonia  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Bronchitis  1  1/362 (0.28%)  1 1/360 (0.28%)  1 0/360 (0.00%)  0
Diverticulitis  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Gangrene  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Groin abscess  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Hepatitis B  1  1/362 (0.28%)  1 1/360 (0.28%)  1 0/360 (0.00%)  0
Infected skin ulcer  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Pneumonia  1  2/362 (0.55%)  2 0/360 (0.00%)  0 1/360 (0.28%)  1
Pyelonephritis  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Sepsis  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Jaw fracture  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Laceration  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Pneumocephalus  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Investigations       
Weight decreased  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Metabolism and nutrition disorders       
Hypoglycaemia  1  1/362 (0.28%)  1 1/360 (0.28%)  1 0/360 (0.00%)  0
Hyponatraemia  1  2/362 (0.55%)  2 0/360 (0.00%)  0 0/360 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Chondropathy  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Intervertebral disc protrusion  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Lumbar spinal stenosis  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Osteoarthritis  1  1/362 (0.28%)  1 2/360 (0.56%)  2 1/360 (0.28%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Nasopharyngeal cancer  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Pancreatic carcinoma metastatic  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Renal cell carcinoma  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Thyroid neoplasm  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Nervous system disorders       
Carotid artery stenosis  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Cerebrovascular accident  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Hypoglycaemic unconsciousness  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Ischaemic stroke  1  1/362 (0.28%)  1 1/360 (0.28%)  1 0/360 (0.00%)  0
Migraine with aura  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Sciatica  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Transient ischaemic attack  1  0/362 (0.00%)  0 2/360 (0.56%)  2 0/360 (0.00%)  0
VIIth nerve paralysis  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Renal failure  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Reproductive system and breast disorders       
Endometrial hyperplasia  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Bronchial hyperreactivity  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Skin and subcutaneous tissue disorders       
Skin ulcer  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Surgical and medical procedures       
Carotid endarterectomy  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Coronary arterial stent insertion  1  0/362 (0.00%)  0 1/360 (0.28%)  1 0/360 (0.00%)  0
Eyelid operation  1  0/362 (0.00%)  0 0/360 (0.00%)  0 1/360 (0.28%)  1
Vascular disorders       
Peripheral arterial occlusive disease  1  1/362 (0.28%)  1 0/360 (0.00%)  0 0/360 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Semaglutide 0.5mg/Week Semaglutide 1.0 mg/Week Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   172/362 (47.51%)      192/360 (53.33%)      107/360 (29.72%)    
Gastrointestinal disorders       
Diarrhoea  1  59/362 (16.30%)  67 69/360 (19.17%)  118 16/360 (4.44%)  18
Dyspepsia  1  12/362 (3.31%)  24 24/360 (6.67%)  39 2/360 (0.56%)  2
Gastrooesophageal reflux disease  1  4/362 (1.10%)  4 19/360 (5.28%)  20 3/360 (0.83%)  4
Nausea  1  77/362 (21.27%)  101 80/360 (22.22%)  117 12/360 (3.33%)  15
Vomiting  1  24/362 (6.63%)  28 37/360 (10.28%)  119 10/360 (2.78%)  12
Infections and infestations       
Nasopharyngitis  1  45/362 (12.43%)  58 29/360 (8.06%)  37 44/360 (12.22%)  51
Upper respiratory tract infection  1  10/362 (2.76%)  10 14/360 (3.89%)  16 24/360 (6.67%)  25
Investigations       
Lipase increased  1  36/362 (9.94%)  39 30/360 (8.33%)  32 15/360 (4.17%)  17
Metabolism and nutrition disorders       
Decreased appetite  1  25/362 (6.91%)  34 23/360 (6.39%)  23 1/360 (0.28%)  1
Musculoskeletal and connective tissue disorders       
Back pain  1  11/362 (3.04%)  11 18/360 (5.00%)  20 7/360 (1.94%)  10
Nervous system disorders       
Headache  1  19/362 (5.25%)  40 23/360 (6.39%)  33 20/360 (5.56%)  26
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator (s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for upto 60 days to protect intellectual property.
Results Point of Contact
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
Publications of Results:
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT02128932     History of Changes
Other Study ID Numbers: NN9535-3625
2013-004392-12 ( EudraCT Number )
U1111-1146-0211 ( Other Identifier: WHO )
NL47781.018.14 ( Registry Identifier: National Registry in The Netherlands )
First Submitted: April 24, 2014
First Posted: May 1, 2014
Results First Submitted: December 14, 2017
Results First Posted: March 8, 2018
Last Update Posted: June 13, 2019