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SUSTAIN™ 3: Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT01885208
Collaborator
(none)
813
Enrollment
146
Locations
2
Arms
19.3
Actual Duration (Months)
5.6
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted in Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of semaglutide once-weekly versus exenatide ER (extended release) 2.0 mg once-weekly as add-on to 1-2 oral antidiabetic drugs (OADs) in subjects with type 2 diabetes.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
813 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes (SUSTAIN™ 3 - vs. QW GLP-1)
Actual Study Start Date :
Dec 2, 2013
Actual Primary Completion Date :
Jul 13, 2015
Actual Study Completion Date :
Jul 13, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Semaglutide 1.0 mg

Drug: semaglutide
One dose of 1.0 mg semaglutide administered subcutaneously (s.c., under the skin) once-weekly
Active Comparator: Exenatide ER 2.0 mg

Drug: exenatide
One dose of 2.0 mg exenatide ER administered subcutaneously (s.c., under the skin) once-weekly
Other Names:
  • Bydureon®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in HbA1c (Glycosylated Haemoglobin) [Week 0, week 56]

      Mean change in HbA1c from baseline to week 56.

    Secondary Outcome Measures

    1. Change From Baseline in Body Weight [Week 0, week 56]

      Mean change in body weight from baseline to week 56.

    2. Change From Baseline in Fasting Plasma Glucose (FPG) [Week 0, week 56]

      Mean change in FPG from baseline to week 56.

    3. Change From Baseline in Systolic and Diastolic Blood Pressure [Week 0, week 56]

      Mean changes in systolic and diastolic blood pressure from baseline to week 56.

    4. Change From Baseline in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) [Week 0, week 56]

      The Diabetes Treatment Satisfaction Questionnaire (DTSQs) was used to assess a subject's treatment satisfaction. This questionnaire contained 8 components and measures 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.

    5. Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target: (Yes/no) [After 56 weeks' treatment]

      The endpoint considered HbA1c ≤6.5% (48 mmol/mol) as per the AACE target after 56 weeks of treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria: - Subjects diagnosed with type 2 diabetes and on stable diabetes treatment with 1-2 OADs (Metformin equal to or above 1500 mg or maximum tolerated dose and/or thiazolidinedione (TZD) and sulfonylureas (SUs) equal to or above half of maximum dose allowed according to national label) for at least 90 days prior to screening. Stable is defined as unchanged medication and unchanged dose - HbA1c 7.0 - 10.5 % (53 - 91 mmol/mol) (both inclusive) Exclusion Criteria: - Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 week follow-up period (adequate contraceptive measures as required by local law or practice) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (7 days or less in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novo Nordisk Investigational Site Anniston Alabama United States 36207
    2 Novo Nordisk Investigational Site Birmingham Alabama United States 35216
    3 Novo Nordisk Investigational Site Pell City Alabama United States 35128
    4 Novo Nordisk Investigational Site Glendale Arizona United States 85306-4652
    5 Novo Nordisk Investigational Site Mesa Arizona United States 85213
    6 Novo Nordisk Investigational Site Phoenix Arizona United States 85027
    7 Novo Nordisk Investigational Site Burbank California United States 91505
    8 Novo Nordisk Investigational Site Hawaiian Gardens California United States 90716
    9 Novo Nordisk Investigational Site Lomita California United States 90717
    10 Novo Nordisk Investigational Site Los Angeles California United States 90017
    11 Novo Nordisk Investigational Site Los Angeles California United States 90022
    12 Novo Nordisk Investigational Site Los Angeles California United States 90057
    13 Novo Nordisk Investigational Site Northridge California United States 91324
    14 Novo Nordisk Investigational Site Northridge California United States 91325
    15 Novo Nordisk Investigational Site San Diego California United States 92108
    16 Novo Nordisk Investigational Site Tustin California United States 92780
    17 Novo Nordisk Investigational Site Colorado Springs Colorado United States 80906
    18 Novo Nordisk Investigational Site Colorado Springs Colorado United States 80909
    19 Novo Nordisk Investigational Site Bradenton Florida United States 34201
    20 Novo Nordisk Investigational Site Brandon Florida United States 33511
    21 Novo Nordisk Investigational Site Coral Gables Florida United States 33134
    22 Novo Nordisk Investigational Site Hialeah Florida United States 33012
    23 Novo Nordisk Investigational Site Jacksonville Florida United States 32207
    24 Novo Nordisk Investigational Site Miami Lakes Florida United States 33016
    25 Novo Nordisk Investigational Site Miami Florida United States 33144
    26 Novo Nordisk Investigational Site Miami Florida United States 33145
    27 Novo Nordisk Investigational Site Miami Florida United States 33174
    28 Novo Nordisk Investigational Site Plantation Florida United States 33324
    29 Novo Nordisk Investigational Site Savannah Georgia United States 31406
    30 Novo Nordisk Investigational Site Chicago Illinois United States 60634
    31 Novo Nordisk Investigational Site Franklin Indiana United States 46131
    32 Novo Nordisk Investigational Site Greenfield Indiana United States 46140
    33 Novo Nordisk Investigational Site Muncie Indiana United States 47304
    34 Novo Nordisk Investigational Site Louisville Kentucky United States 40213
    35 Novo Nordisk Investigational Site Madisonville Kentucky United States 42431
    36 Novo Nordisk Investigational Site Hyattsville Maryland United States 20782
    37 Novo Nordisk Investigational Site Kalamazoo Michigan United States 49009
    38 Novo Nordisk Investigational Site Saint Louis Missouri United States 63141
    39 Novo Nordisk Investigational Site Las Vegas Nevada United States 89103
    40 Novo Nordisk Investigational Site Mine Hill New Jersey United States 07803
    41 Novo Nordisk Investigational Site Albuquerque New Mexico United States 87102
    42 Novo Nordisk Investigational Site North Massapequa New York United States 11758-1802
    43 Novo Nordisk Investigational Site Syracuse New York United States 13210
    44 Novo Nordisk Investigational Site West Seneca New York United States 14224
    45 Novo Nordisk Investigational Site Greensboro North Carolina United States 27408
    46 Novo Nordisk Investigational Site Hickory North Carolina United States 28601
    47 Novo Nordisk Investigational Site Whiteville North Carolina United States 28472
    48 Novo Nordisk Investigational Site Akron Ohio United States 44311
    49 Novo Nordisk Investigational Site Cincinnati Ohio United States 45255
    50 Novo Nordisk Investigational Site Cleveland Ohio United States 44122
    51 Novo Nordisk Investigational Site Delaware Ohio United States 43015
    52 Novo Nordisk Investigational Site Corvallis Oregon United States 97330-3737
    53 Novo Nordisk Investigational Site Portland Oregon United States 97210
    54 Novo Nordisk Investigational Site Portland Oregon United States 97239
    55 Novo Nordisk Investigational Site Lansdale Pennsylvania United States 19446-1002
    56 Novo Nordisk Investigational Site Norristown Pennsylvania United States 19401
    57 Novo Nordisk Investigational Site Charleston South Carolina United States 29407
    58 Novo Nordisk Investigational Site Mount Pleasant South Carolina United States 29464
    59 Novo Nordisk Investigational Site Murrells Inlet South Carolina United States 29576
    60 Novo Nordisk Investigational Site Spartanburg South Carolina United States 29303
    61 Novo Nordisk Investigational Site Chattanooga Tennessee United States 37404
    62 Novo Nordisk Investigational Site Austin Texas United States 78731
    63 Novo Nordisk Investigational Site Carrollton Texas United States 75010
    64 Novo Nordisk Investigational Site Dallas Texas United States 75225
    65 Novo Nordisk Investigational Site Dallas Texas United States 75390-8858
    66 Novo Nordisk Investigational Site Fort Worth Texas United States 76117
    67 Novo Nordisk Investigational Site Houston Texas United States 77008
    68 Novo Nordisk Investigational Site Houston Texas United States 77024
    69 Novo Nordisk Investigational Site Houston Texas United States 77040
    70 Novo Nordisk Investigational Site Houston Texas United States 77072
    71 Novo Nordisk Investigational Site Irving Texas United States 75039
    72 Novo Nordisk Investigational Site Katy Texas United States 77450
    73 Novo Nordisk Investigational Site San Antonio Texas United States 78245
    74 Novo Nordisk Investigational Site Sugar Land Texas United States 77478
    75 Novo Nordisk Investigational Site Sugar Land Texas United States 77479
    76 Novo Nordisk Investigational Site Alexandria Virginia United States 22304
    77 Novo Nordisk Investigational Site Buenos Aires Argentina C1250AAN
    78 Novo Nordisk Investigational Site Buenos Aires Argentina C1425AGC
    79 Novo Nordisk Investigational Site Caba Argentina C1179AAB
    80 Novo Nordisk Investigational Site Lanus Este Argentina B1824KAJ
    81 Novo Nordisk Investigational Site Mar del Plata Argentina B7600GWV
    82 Novo Nordisk Investigational Site Karlovac Croatia 47000
    83 Novo Nordisk Investigational Site Osijek Croatia 31 000
    84 Novo Nordisk Investigational Site Slavonski Brod Croatia 35 000
    85 Novo Nordisk Investigational Site Virovitica Croatia 33000
    86 Novo Nordisk Investigational Site Zagreb Croatia 10 000
    87 Novo Nordisk Investigational Site Helsinki Finland 00260
    88 Novo Nordisk Investigational Site Helsinki Finland FI-00100
    89 Novo Nordisk Investigational Site Kerava Finland FI-04200
    90 Novo Nordisk Investigational Site Oulu Finland 90220
    91 Novo Nordisk Investigational Site Turku Finland 20520
    92 Novo Nordisk Investigational Site Chalons-en-Champagne Cedex France 51005
    93 Novo Nordisk Investigational Site Corbeil Essonnes France 91106
    94 Novo Nordisk Investigational Site LA ROCHELLE cedex France 17019
    95 Novo Nordisk Investigational Site Le Creusot France 71200
    96 Novo Nordisk Investigational Site Nanterre France 92014
    97 Novo Nordisk Investigational Site Roubaix France 59100
    98 Novo Nordisk Investigational Site Strasbourg France 67000
    99 Novo Nordisk Investigational Site Venissieux France 69200
    100 Novo Nordisk Investigational Site Dresden Germany 01219
    101 Novo Nordisk Investigational Site Dresden Germany 01307
    102 Novo Nordisk Investigational Site Duisburg Germany 47051
    103 Novo Nordisk Investigational Site Hohenmölsen Germany 06679
    104 Novo Nordisk Investigational Site Mannheim Germany 68163
    105 Novo Nordisk Investigational Site Oldenburg Germany 23758
    106 Novo Nordisk Investigational Site Rehlingen-Siersburg Germany 66780
    107 Novo Nordisk Investigational Site Völklingen Germany 66333
    108 Novo Nordisk Investigational Site Athens Greece GR-12462
    109 Novo Nordisk Investigational Site Athens Greece GR-14233
    110 Novo Nordisk Investigational Site Athens Greece GR-17562
    111 Novo Nordisk Investigational Site Piraeus Greece GR-18536
    112 Novo Nordisk Investigational Site Thessaloniki Greece GR-54636
    113 Novo Nordisk Investigational Site Thessaloniki Greece GR-57010
    114 Novo Nordisk Investigational Site Bologna Italy 40138
    115 Novo Nordisk Investigational Site Città di Castello Italy 06012
    116 Novo Nordisk Investigational Site Milano Italy 20132
    117 Novo Nordisk Investigational Site Palermo Italy 90127
    118 Novo Nordisk Investigational Site Pavia Italy 27100
    119 Novo Nordisk Investigational Site Roma Italy 00161
    120 Novo Nordisk Investigational Site Siena Italy 53100
    121 Novo Nordisk Investigational Site Amsterdam Netherlands 1066 EC
    122 Novo Nordisk Investigational Site Apeldoorn Netherlands 7334 DZ
    123 Novo Nordisk Investigational Site Delft Netherlands 2625 AD
    124 Novo Nordisk Investigational Site Hoofddorp Netherlands 2134 TM
    125 Novo Nordisk Investigational Site Leeuwarden Netherlands 8934 AD
    126 Novo Nordisk Investigational Site Rotterdam Netherlands 3021 HC
    127 Novo Nordisk Investigational Site Rotterdam Netherlands 3039 BD
    128 Novo Nordisk Investigational Site Venlo Netherlands 5912 BL
    129 Novo Nordisk Investigational Site Zoetermeer Netherlands 2725 NA
    130 Novo Nordisk Investigational Site Caguas Puerto Rico 00725
    131 Novo Nordisk Investigational Site Manati Puerto Rico 00674
    132 Novo Nordisk Investigational Site Belgrade Serbia 11000
    133 Novo Nordisk Investigational Site Belgrade Serbia 11080
    134 Novo Nordisk Investigational Site Kragujevac Serbia 34000
    135 Novo Nordisk Investigational Site Novi Sad Serbia 21000
    136 Novo Nordisk Investigational Site Basel Switzerland 4031
    137 Novo Nordisk Investigational Site Genève 14 Switzerland 1211
    138 Novo Nordisk Investigational Site Luzern 16 Switzerland 6000
    139 Novo Nordisk Investigational Site St. Gallen Switzerland 9007
    140 Novo Nordisk Investigational Site Zollikerberg Switzerland 8125
    141 Novo Nordisk Investigational Site Ayr United Kingdom KA6 6DX
    142 Novo Nordisk Investigational Site Bath United Kingdom BA1 3NG
    143 Novo Nordisk Investigational Site Bradford-on-Avon United Kingdom BA15 1DQ
    144 Novo Nordisk Investigational Site Haxey United Kingdom DN9 2HY
    145 Novo Nordisk Investigational Site Headington United Kingdom OX3 7LE
    146 Novo Nordisk Investigational Site Rotherham United Kingdom S651DA

    Sponsors and Collaborators

    • Novo Nordisk A/S

    Investigators

    • Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT01885208
    Other Study ID Numbers:
    • NN9535-3624
    • 2012-004826-92
    • U1111-1135-8647
    First Posted:
    Jun 24, 2013
    Last Update Posted:
    Jun 13, 2019
    Last Verified:
    May 1, 2019
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Exenatide

    Study Results

    Participant Flow

    Recruitment Details Out of 146 sites selected for recruitment, 138 sites in 12 countries randomised subjects to the treatment viz. Argentina: 4 sites; Croatia: 5 sites; Finland: 5 sites; France: 7 sites; Germany: 7 sites; Greece: 5 sites; Italy: 6 sites; Netherlands: 8 sites; Serbia: 5 sites; Switzerland: 5 sites; United Kingdom: 6 sites and United States: 75 sites
    Pre-assignment Detail
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects on exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Period Title: Overall Study
    STARTED 406 407
    Exposed 404 405
    Premature Discontinuation of Treatment 82 85
    COMPLETED 374 369
    NOT COMPLETED 32 38

    Baseline Characteristics

    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg Total
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed. Total of all reporting groups
    Overall Participants 404 405 809
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.4
    (10.3)
    56.7
    (11.1)
    56.6
    (10.7)
    Sex: Female, Male (Count of Participants)
    Female
    185
    45.8%
    177
    43.7%
    362
    44.7%
    Male
    219
    54.2%
    228
    56.3%
    447
    55.3%
    Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of glycosylated haemoglobin]
    8.36
    (0.95)
    8.33
    (0.96)
    8.35
    (0.95)
    Body Weight (kilogram (s)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram (s)]
    96.21
    (22.5)
    95.37
    (20.46)
    95.79
    (21.49)
    Fasting Plasma Glucose (mg/ dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/ dL]
    190.5
    (48.06)
    187.5
    (49.41)
    189.0
    (48.74)
    Systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm Hg]
    133.35
    (14.87)
    133.66
    (14.25)
    133.51
    (14.55)
    Diastolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm Hg]
    80.23
    (8.67)
    79.57
    (8.8)
    79.90
    (8.73)
    Patient-reported outcome: Diabetes Treatment Satisfaction Questionnaire (DTSQ) (Units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Units on a scale]
    27.35
    (6.55)
    27.23
    (6.62)
    27.29
    (6.58)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in HbA1c (Glycosylated Haemoglobin)
    Description Mean change in HbA1c from baseline to week 56.
    Time Frame Week 0, week 56

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin]
    -1.54
    (0.06)
    -0.92
    (0.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Semaglutide 1.0 mg, Exenatide ER 2.0 mg
    Comments The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
    Type of Statistical Test Non-Inferiority
    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 exenatide ER 2.0 mg was below the pre-specified non-inferiority margin (0.3 %).
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Treatment difference
    Estimated Value -0.62
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Semaglutide 1.0 mg, Exenatide ER 2.0 mg
    Comments The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
    Type of Statistical Test Superiority
    Comments Superiority was concluded if the upper limit of the two-sided 95% confidence interval for the estimated treatment difference between semaglutide 1.0 mg and exenatide ER 2.0 mg was below the pre-specified superiority margin (0 %).
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Treatment difference
    Estimated Value -0.62
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description Mean change in body weight from baseline to week 56.
    Time Frame Week 0, week 56

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Least Squares Mean (Standard Error) [kilograms]
    -5.63
    (0.29)
    -1.85
    (0.29)
    3. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose (FPG)
    Description Mean change in FPG from baseline to week 56.
    Time Frame Week 0, week 56

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Least Squares Mean (Standard Error) [mg/dL]
    -51.22
    (2.36)
    -36.1
    (2.45)
    4. Secondary Outcome
    Title Change From Baseline in Systolic and Diastolic Blood Pressure
    Description Mean changes in systolic and diastolic blood pressure from baseline to week 56.
    Time Frame Week 0, week 56

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Systolic blood pressure
    -4.6
    (0.68)
    -2.23
    (0.7)
    Diastolic blood pressure
    -1.0
    (0.45)
    -0.1
    (0.46)
    5. Secondary Outcome
    Title Change From Baseline in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs)
    Description The Diabetes Treatment Satisfaction Questionnaire (DTSQs) was used to assess a subject's treatment satisfaction. This questionnaire contained 8 components and measures 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.
    Time Frame Week 0, week 56

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Least Squares Mean (Standard Error) [Units on a scale]
    4.98
    (0.26)
    3.96
    (0.27)
    6. Secondary Outcome
    Title Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target: (Yes/no)
    Description The endpoint considered HbA1c ≤6.5% (48 mmol/mol) as per the AACE target after 56 weeks of treatment.
    Time Frame After 56 weeks' treatment

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) included all randomised subjects who had received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg.
    Arm/Group Title Semaglutide 1.0 mg Exenatide ER 2.0 mg
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD) therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg (Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    Measure Participants 404 405
    Yes
    190
    47%
    89
    22%
    No
    214
    53%
    316
    78%

    Adverse Events

    Time Frame All adverse events are treatment-emergent adverse events (TEAEs). 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 0-56 treatment period) and no later than the date of last dose + 42 days of follow-up.
    Adverse Event Reporting Description The safety analysis set (SAS) included all randomised subjects who have received at least one dose of randomised semaglutide 1.0 mg or exenatide ER 2.0 mg. Subjects in the SAS contributed to the evaluation based on the treatment actually received.
    Arm/Group Title Sema 1.0 mg Exenatide ER
    Arm/Group Description Subjects randomised to semaglutide followed a fixed dose-escalation regimen for a period of 56 weeks. Subjects started with once-weekly doses of 0.25 mg for 4 weeks, then escalated to doses of 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and was to be administered subcutaneously (s.c.; under the skin) either in the thigh, abdomen or upper arm at the same weekday. All subjects continued their pre-trial treatment of 1-2 oral anti-diabetes drug (OAD)therapy throughout the trial, unless rescue medication was needed. Subjects randomised to exenatide extended release (ER) 2.0 mg(Bydureon®) were treated with the same 2.0 mg dose for a period of 56 weeks. Exenatide one vial of 2 mg exenatide ER was supplied in a pre-filled syringe of 0.65 mL solvent and to be administrated subcutaneously (s.c.; under the skin) once weekly through out the trial. All subjects continued their pre-trial treatment of 1-2 OAD therapy entire trial, unless rescue medication was needed.
    All Cause Mortality
    Sema 1.0 mg Exenatide ER
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sema 1.0 mg Exenatide ER
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/404 (9.4%) 24/405 (5.9%)
    Cardiac disorders
    Angina pectoris 1/404 (0.2%) 1 0/405 (0%) 0
    Arteriosclerosis coronary artery 1/404 (0.2%) 1 0/405 (0%) 0
    Atrial fibrillation 0/404 (0%) 0 3/405 (0.7%) 3
    Atrioventricular block complete 0/404 (0%) 0 1/405 (0.2%) 1
    Coronary artery disease 1/404 (0.2%) 1 0/405 (0%) 0
    Coronary artery insufficiency 1/404 (0.2%) 1 0/405 (0%) 0
    Coronary artery stenosis 1/404 (0.2%) 1 0/405 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/404 (0%) 0 1/405 (0.2%) 1
    Gastrointestinal disorders
    Abdominal pain 0/404 (0%) 0 1/405 (0.2%) 1
    Crohn's disease 1/404 (0.2%) 1 0/405 (0%) 0
    Diverticulum 1/404 (0.2%) 1 0/405 (0%) 0
    Duodenal ulcer 1/404 (0.2%) 1 0/405 (0%) 0
    Duodenitis 0/404 (0%) 0 1/405 (0.2%) 1
    Gastric ulcer 1/404 (0.2%) 1 0/405 (0%) 0
    Gastritis 0/404 (0%) 0 1/405 (0.2%) 1
    Pancreatitis 3/404 (0.7%) 3 0/405 (0%) 0
    General disorders
    Chest discomfort 1/404 (0.2%) 1 0/405 (0%) 0
    Chest pain 1/404 (0.2%) 1 0/405 (0%) 0
    Surgical failure 1/404 (0.2%) 1 0/405 (0%) 0
    Hepatobiliary disorders
    Cholecystitis acute 1/404 (0.2%) 1 0/405 (0%) 0
    Cholelithiasis 0/404 (0%) 0 1/405 (0.2%) 1
    Infections and infestations
    Cellulitis 1/404 (0.2%) 1 1/405 (0.2%) 1
    Encephalitis 1/404 (0.2%) 1 0/405 (0%) 0
    Gastroenteritis 0/404 (0%) 0 2/405 (0.5%) 2
    Pneumonia 1/404 (0.2%) 1 1/405 (0.2%) 1
    Respiratory tract infection 1/404 (0.2%) 1 0/405 (0%) 0
    Sepsis 1/404 (0.2%) 1 0/405 (0%) 0
    Urinary tract infection 0/404 (0%) 0 1/405 (0.2%) 1
    Urosepsis 1/404 (0.2%) 1 0/405 (0%) 0
    Vestibular neuronitis 1/404 (0.2%) 1 0/405 (0%) 0
    Injury, poisoning and procedural complications
    Spinal compression fracture 1/404 (0.2%) 1 0/405 (0%) 0
    Investigations
    HIV test positive 1/404 (0.2%) 1 0/405 (0%) 0
    Liver function test abnormal 1/404 (0.2%) 1 0/405 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 1/404 (0.2%) 1 0/405 (0%) 0
    Diabetic ketoacidosis 1/404 (0.2%) 1 0/405 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/404 (0%) 0 1/405 (0.2%) 1
    Back pain 1/404 (0.2%) 1 0/405 (0%) 0
    Spinal disorder 1/404 (0.2%) 1 0/405 (0%) 0
    Spondylolisthesis 1/404 (0.2%) 1 0/405 (0%) 0
    Tendonitis 0/404 (0%) 0 1/405 (0.2%) 1
    Vertebral foraminal stenosis 1/404 (0.2%) 1 0/405 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign renal neoplasm 1/404 (0.2%) 1 0/405 (0%) 0
    Breast cancer 1/404 (0.2%) 1 1/405 (0.2%) 1
    Castleman's disease 1/404 (0.2%) 1 0/405 (0%) 0
    Endometrial adenocarcinoma 1/404 (0.2%) 1 0/405 (0%) 0
    Endometrial cancer stage I 0/404 (0%) 0 1/405 (0.2%) 1
    Follicular thyroid cancer 1/404 (0.2%) 1 0/405 (0%) 0
    Hepatocellular carcinoma 1/404 (0.2%) 1 0/405 (0%) 0
    Invasive lobular breast carcinoma 1/404 (0.2%) 1 0/405 (0%) 0
    Prostate cancer 1/404 (0.2%) 1 0/405 (0%) 0
    Nervous system disorders
    Aphasia 0/404 (0%) 0 1/405 (0.2%) 1
    Dizziness 1/404 (0.2%) 1 1/405 (0.2%) 1
    Ischaemic stroke 1/404 (0.2%) 1 0/405 (0%) 0
    Transient ischaemic attack 0/404 (0%) 0 1/405 (0.2%) 1
    Psychiatric disorders
    Anxiety 1/404 (0.2%) 1 0/405 (0%) 0
    Renal and urinary disorders
    Glycosuria 1/404 (0.2%) 1 0/405 (0%) 0
    Hydronephrosis 1/404 (0.2%) 1 0/405 (0%) 0
    Nephrolithiasis 2/404 (0.5%) 2 0/405 (0%) 0
    Renal colic 0/404 (0%) 0 1/405 (0.2%) 1
    Urethral stenosis 0/404 (0%) 0 1/405 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/404 (0%) 0 1/405 (0.2%) 1
    Skin and subcutaneous tissue disorders
    Blister 0/404 (0%) 0 1/405 (0.2%) 1
    Skin ulcer 0/404 (0%) 0 1/405 (0.2%) 1
    Surgical and medical procedures
    Abortion induced 0/404 (0%) 0 1/405 (0.2%) 1
    Cardiac ablation 1/404 (0.2%) 1 0/405 (0%) 0
    Coronary arterial stent insertion 1/404 (0.2%) 1 0/405 (0%) 0
    Coronary artery bypass 2/404 (0.5%) 2 0/405 (0%) 0
    Meniscus removal 1/404 (0.2%) 1 0/405 (0%) 0
    Other (Not Including Serious) Adverse Events
    Sema 1.0 mg Exenatide ER
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 194/404 (48%) 187/405 (46.2%)
    Gastrointestinal disorders
    Constipation 26/404 (6.4%) 28 21/405 (5.2%) 26
    Diarrhoea 46/404 (11.4%) 86 34/405 (8.4%) 58
    Dyspepsia 27/404 (6.7%) 33 19/405 (4.7%) 23
    Nausea 90/404 (22.3%) 159 48/405 (11.9%) 70
    Vomiting 29/404 (7.2%) 37 25/405 (6.2%) 40
    General disorders
    Injection site nodule 0/404 (0%) 0 49/405 (12.1%) 55
    Infections and infestations
    Nasopharyngitis 39/404 (9.7%) 46 38/405 (9.4%) 51
    Investigations
    Lipase increased 41/404 (10.1%) 51 49/405 (12.1%) 64
    Metabolism and nutrition disorders
    Decreased appetite 32/404 (7.9%) 34 21/405 (5.2%) 24
    Nervous system disorders
    Headache 38/404 (9.4%) 81 39/405 (9.6%) 65

    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 less than 60 days to protect intellectual property".

    Results Point of Contact

    Name/Title Clinical Reporting Anchor and Disclosure (1452)
    Organization Novo Nordisk A/S
    Phone
    Email clinicaltrials@novonordisk.com
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT01885208
    Other Study ID Numbers:
    • NN9535-3624
    • 2012-004826-92
    • U1111-1135-8647
    First Posted:
    Jun 24, 2013
    Last Update Posted:
    Jun 13, 2019
    Last Verified:
    May 1, 2019