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Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6)

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ClinicalTrials.gov Identifier: NCT01720446
Recruitment Status : Completed
First Posted : November 2, 2012
Results First Posted : March 15, 2018
Last Update Posted : March 15, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: semaglutide
Drug: placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The trial was conducted at 229 sites in 20 countries. Country (sites): Algeria (4), Argentina (7), Australia (8), Brazil (8), Bulgaria (5), Canada (13), Denmark (5), Germany (7), Israel (6), Italy (6), Malaysia (6), Mexico (9), Poland (5), Russia (11), Spain (6), Taiwan (4), Thailand (5), Turkey (10), United Kingdom (8) and United States (96).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects could be anti-glycaemic drug naïve, or treated with 1 or 2 oral anti diabetic drugs (OADs), or treated with human NPH insulin or long-acting insulin analogue or pre-mixed insulin, alone or in combination with 1 or 2 OAD(s).

Reporting Groups
  Description
Semaglutide 0.5 mg Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
Semaglutide 1.0 mg Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Placebo 0.5 mg Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
Placebo 1.0 mg Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.

Participant Flow:   Overall Study
    Semaglutide 0.5 mg   Semaglutide 1.0 mg   Placebo 0.5 mg   Placebo 1.0 mg
STARTED   826   822   824   825 
Premature Treatment Discontinuers   164 [1]   186 [1]   151 [1]   159 [1] 
COMPLETED   812 [2]   811 [2]   804 [2]   805 [2] 
NOT COMPLETED   14   11   20   20 
Lost to Follow-up                12                6                16                16 
Withdrawal by Subject                2                5                4                4 
[1] Premature treatment discontinuers were allowed to continue participation in the trial.
[2] Subjects who did not permanently discontinue treatment prematurely.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on full analysis set which included all randomised subjects.

Reporting Groups
  Description
Semaglutide 0.5 mg Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
Semaglutide 1.0 mg Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Placebo 0.5 mg Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks.
Placebo 1.0 mg Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks.
Total Total of all reporting groups

Baseline Measures
   Semaglutide 0.5 mg   Semaglutide 1.0 mg   Placebo 0.5 mg   Placebo 1.0 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 826   822   824   825   3297 
Age, Customized 
[Units: Participants]
         
50-64 years   440   415   419   425   1699 
65-74 years   312   324   324   317   1277 
75-84 years   71   76   75   79   301 
85 and over   3   7   6   4   20 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      331  40.1%      304  37.0%      342  41.5%      318  38.5%      1295  39.3% 
Male      495  59.9%      518  63.0%      482  58.5%      507  61.5%      2002  60.7% 
Glycosylated haemoglobin 
[Units: Percentage of glycosylated haemoglobin]
Mean (Standard Deviation)
 8.67  (1.39)   8.73  (1.51)   8.70  (1.49)   8.70  (1.45)   8.70  (1.46) 
Fasting plasma glucose 
[Units: mg/dL]
Mean (Standard Deviation)
 185.4  (66.09)   182.9  (68.04)   185.8  (68.23)   184.6  (63.08)   184.7  (66.37) 
Body weight 
[Units: Kg]
Mean (Standard Deviation)
 91.80  (20.25)   92.86  (21.05)   91.83  (20.35)   91.90  (20.75)   92.09  (20.60) 
LDL-cholesterol 
[Units: mg/dL]
Mean (Standard Deviation)
 89.62  (39.08)   89.72  (34.49)   89.01  (38.35)   91.14  (37.90)   89.87  (37.49) 
HDL-cholesterol 
[Units: mg/dL]
Mean (Standard Deviation)
 45.92  (13.00)   44.97  (12.42)   45.82  (12.92)   44.61  (12.26)   45.33  (12.66) 
Systolic BP 
[Units: mmHg]
Mean (Standard Deviation)
 136.1  (17.97)   135.8  (16.96)   135.8  (16.16)   134.8  (17.45)   135.6  (17.15) 
Diastolic BP 
[Units: mmHg]
Mean (Standard Deviation)
 77.10  (9.78)   76.88  (10.21)   77.54  (9.85)   76.66  (10.21)   77.05  (10.02) 
Pulse rate 
[Units: Beats/min]
Mean (Standard Deviation)
 72.69  (11.22)   71.53  (10.86)   72.01  (10.62)   71.95  (10.92)   72.05  (10.91) 
Total cholesterol 
[Units: mg/dL]
Geometric Mean (Full Range)
 165.38 
 (65.25 to 632.43) 
 164.96 
 (79.54 to 562.16) 
 164.38 
 (70.27 to 378.38) 
 165.97 
 (64.86 to 537.07) 
 165.17 
 (64.86 to 632.43) 
Triglycerides 
[Units: mg/dL]
Geometric Mean (Full Range)
 163.66 
 (27.59 to 1913.50) 
 158.93 
 (10.68 to 3378.44) 
 162.30 
 (30.26 to 1438.24) 
 163.00 
 (35.60 to 2435.93) 
 161.96 
 (10.68 to 3378.44) 
Free fatty acids 
[Units: mmol/L]
Geometric Mean (Full Range)
 0.83 
 (0.04 to 3.82) 
 0.80 
 (0.04 to 4.20) 
 0.83 
 (0.04 to 3.34) 
 0.81 
 (0.04 to 4.22) 
 0.82 
 (0.04 to 4.22) 


  Outcome Measures

1.  Primary:   Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke   [ Time Frame: Time from randomisation up to end of follow-up (scheduled at week 109) ]

2.  Secondary:   Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome   [ Time Frame: Time from randomisation up to end of follow-up (scheduled at week 109) ]

3.  Secondary:   Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome   [ Time Frame: Time from randomisation up to end of follow-up (scheduled at week 109) ]

4.  Secondary:   Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke   [ Time Frame: Time from randomisation up to end of follow-up (scheduled at week 109) ]

5.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c)   [ Time Frame: Week 0, up to week 104 ]

6.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose   [ Time Frame: Week 0, up to week 104 ]

7.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight   [ Time Frame: Week 0, up to week 104 ]

8.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile   [ Time Frame: Week 0, up to week 104 ]

9.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio   [ Time Frame: Week 0, up to week 104 ]

10.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs   [ Time Frame: Week 0, up to week 104 ]

11.  Secondary:   Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events   [ Time Frame: Week 0 - 109 ]

12.  Secondary:   Incidence During the Trial in Other Treatment Outcomes: Adverse Events   [ Time Frame: Weeks 0-109 ]

13.  Secondary:   Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies   [ Time Frame: Weeks 0-109 ]

14.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO)   [ Time Frame: Week 0, up to week 104 ]

15.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids)   [ Time Frame: Week 0, up to week 104 ]

16.  Secondary:   Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate)   [ Time Frame: Week 0, up to week 104 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01720446     History of Changes
Other Study ID Numbers: NN9535-3744
2012-002839-28 ( EudraCT Number )
U1111-1131-7227 ( Other Identifier: WHO )
First Submitted: October 29, 2012
First Posted: November 2, 2012
Results First Submitted: December 14, 2017
Results First Posted: March 15, 2018
Last Update Posted: March 15, 2018