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CompletedNCT00082407Updated Apr 7, 2015Results posted

Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

A Phase 3 interventional study of exenatide and biphasic insulin aspart in Diabetes Mellitus, Type 2, sponsored by AstraZeneca. Completed at 69 sites in 12 countries. Open to participants aged 30 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-04-07.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
505
Allocation
Randomized
Ages
30 Years to 75 Years
Sex
All
01

Study summary

This is a Phase 3, multicenter, open-label, comparator-controlled trial comparing the effect of exenatide twice daily to twice daily biphasic insulin aspart on glycemic control, as measured by hemoglobin A1c (HbA1c).

02

Conditions studied

  • Diabetes Mellitus, Type 2

Keywords

  • diabetes
  • exendin
  • Amylin
  • Lilly
  • insulin aspart
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 505 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. >=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components
  • HbA1c between 7.0% and 11.0%, inclusive.
  • Patients have a body mass index >25kg/m2 and \<40 kg/m2.
  • Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control

Exclusion criteria

Exclusion Criteria:

  • Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study.
  • Patients are employed by Lilly or Amylin.
  • Patients have previously, in this or any other study, received exenatide or glucagon-like peptide-1 analogs.
  • Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
  • Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
  • Patients have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer).
  • Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
  • Patients have a known allergy or hypersensitivity to biphasic insulin aspart, exenatide, or excipients contained in these agents.
  • Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label.
  • Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females.
  • Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range.
  • Patients have known hemoglobinopathy or chronic anemia.
  • Patients have active proliferative retinopathy or macular edema.
  • Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
  • Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
  • Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
  • Patients have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides.
  • Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
  • Patients fail to satisfy the investigator of suitability to participate for any other reason.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
505 participants (actual)

Study arms

  • Experimental
    Exenatide Arm

    subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks

    Drug: exenatide

  • Active comparator
    Biphasic Insulin Aspart Arm

    subcutaneous injection, twice daily; titration to target blood glucose level

    Drug: biphasic insulin aspart

Interventions

  • Drugexenatide

    subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks

    Also known as: Byetta

  • Drugbiphasic insulin aspart

    subcutaneous injection, twice daily; titration to target blood glucose level

    Also known as: NovoLog

06

What researchers measure

Primary outcomes

  1. Change in Glcosylated Hemoglobin (HbA1c)

    Change in HbA1c from baseline to week 52

    Time frame: baseline, week 52

Secondary outcomes

  1. Percentage of Patients Achieving HbA1c <=7%

    Percentage of patients in each arm who had HbA1c \>7% at baseline and had HbA1c \<=7% at week 52 (percentage = \[number of subjects with HbA1c \<=7% at week 52 divided by number of subjects with HbA1c \>7% at baseline\] \* 100%).

    Time frame: 52 weeks

  2. Change in Body Weight

    Change in body weight from baseline to week 52.

    Time frame: baseline, week 52

  3. Change in Fasting Serum Glucose

    Change in fasting serum glucose from baseline to week 52

    Time frame: baseline, week 52

  4. Change in 7-point Self-monitored Blood Glucose (SMBG) Profile

    Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52

    Time frame: baseline, week 52

  5. Percentage of Patients With Hypoglycemic Events

    Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study

    Time frame: 52 weeks

  6. Change in Rate of Hypoglycemic Events

    Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52

    Time frame: baseline, week 52

07

Results

Posted Jul 31, 2013

Participant flow

Participant flow — Overall Study
MilestoneExenatide ArmBiphasic Insulin Aspart Arm
Started255250
Received treatment (intent to treat)253248
Completed199223
Not completed5627
Withdrew: Adverse event200
Withdrew: Protocol violation1412
Withdrew: Patient decision136
Withdrew: Physician decision53
Withdrew: Loss of glucose control22
Withdrew: Death21
Withdrew: Lost to follow-up03

Outcome measures

PrimaryChange in Glcosylated Hemoglobin (HbA1c)

Change in HbA1c from baseline to week 52

Time frame:
baseline, week 52
Reported as:
Least squares mean · percentage
Change in Glcosylated Hemoglobin (HbA1c)
percentageExenatide ArmBiphasic Insulin Aspart Arm
Baseline HbA1c8.59 ± 0.078.65 ± 0.07
Change in HbA1c at week 52-0.98 ± 0.07-0.88 ± 0.07
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · ANCOVA · p = 0.2534 · Mean difference (final values): -0.10 · 95% CI -0.28 to 0.08
SecondaryPercentage of Patients Achieving HbA1c <=7%

Percentage of patients in each arm who had HbA1c \>7% at baseline and had HbA1c \<=7% at week 52 (percentage = \[number of subjects with HbA1c \<=7% at week 52 divided by number of subjects with HbA1c \>7% at baseline\] \* 100%).

Time frame:
52 weeks
Reported as:
Number · percentage of participants
Percentage of Patients Achieving HbA1c <=7%
percentage of participantsExenatide ArmBiphasic Insulin Aspart Arm
Percentage of Patients Achieving HbA1c <=7%31.724.1
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · Fisher Exact · p = 0.0779
SecondaryChange in Body Weight

Change in body weight from baseline to week 52.

Time frame:
baseline, week 52
Reported as:
Least squares mean · kg
Change in Body Weight
kgExenatide ArmBiphasic Insulin Aspart Arm
Baseline body weight85.51 ± 0.9983.38 ± 0.99
Change in body weight at week 52-2.54 ± 0.172.92 ± 0.17
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · ANCOVA · p = 0.0001
SecondaryChange in Fasting Serum Glucose

Change in fasting serum glucose from baseline to week 52

Time frame:
baseline, week 52
Reported as:
Least squares mean · mmol/L
Change in Fasting Serum Glucose
mmol/LExenatide ArmBiphasic Insulin Aspart Arm
Baseline fasting serum glucose11.00 ± 0.1811.30 ± 0.18
Change in fasting serum glucose at week 52-1.75 ± 0.19-1.64 ± 0.19
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · ANCOVA · p = 0.6456
SecondaryChange in 7-point Self-monitored Blood Glucose (SMBG) Profile

Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52

Time frame:
baseline, week 52
Reported as:
Mean · mmol/L
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
mmol/LExenatide ArmBiphasic Insulin Aspart Arm
Pre-breakfast: Baseline SMBG9.57 ± 2.349.86 ± 2.65
Pre-breakfast: Change in SMBG at week 52-1.15 ± 2.60-1.68 ± 2.33
After breakfast: Baseline SMBG12.30 ± 3.0212.71 ± 3.03
After breakfast: Change in SMBG at week 52-3.83 ± 3.30-3.06 ± 3.26
Pre-lunch: Baseline SMBG9.38 ± 2.869.86 ± 3.30
Pre-lunch: Change in SMBG at week 52-1.47 ± 3.01-2.40 ± 3.44
After lunch: Baseline SMBG11.18 ± 3.1411.39 ± 3.58
After lunch: Change in SMBG at week 52-1.72 ± 3.48-1.76 ± 3.74
Pre-dinner: Baseline SMBG9.35 ± 2.869.57 ± 3.03
Pre-dinner: Change in SMBG at week 52-1.06 ± 3.25-1.52 ± 3.42
After dinner: Baseline SMBG11.25 ± 3.0411.68 ± 3.27
After dinner: Change in SMBG at week 52-3.11 ± 3.76-2.44 ± 3.69
3:00 AM: Baseline SMBG9.08 ± 2.639.58 ± 3.14
3:00 AM: Change in SMBG at week 52-0.96 ± 3.14-1.95 ± 3.13
SecondaryPercentage of Patients With Hypoglycemic Events

Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study

Time frame:
52 weeks
Reported as:
Number · percentage of participants
Percentage of Patients With Hypoglycemic Events
percentage of participantsExenatide ArmBiphasic Insulin Aspart Arm
Percentage of Patients With Hypoglycemic Events53.051.6
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · Fisher Exact · p = 0.7888
SecondaryChange in Rate of Hypoglycemic Events

Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52

Time frame:
baseline, week 52
Reported as:
Least squares mean · events per 30 days per patient
Change in Rate of Hypoglycemic Events
events per 30 days per patientExenatide ArmBiphasic Insulin Aspart Arm
Baseline event rate0.22 ± 0.070.18 ± 0.07
Change in event rate at week 520.19 ± 0.060.26 ± 0.06
Statistical analysis
  • Exenatide Arm vs Biphasic Insulin Aspart Arm · ANCOVA · p = 0.3722

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Exenatide Arm———
Biphasic Insulin Aspart Arm———
Most frequent serious events
Showing 10 of 41
Most frequent serious events
EventExenatide ArmBiphasic Insulin Aspart Arm
AnemiaBlood and lymphatic system disorders2/2530/248
Angina pectorisCardiac disorders2/2530/248
Myocardial infarctionCardiac disorders2/2530/248
OsteoarthritisMusculoskeletal and connective tissue disorders2/2530/248
Acute coronary syndromeCardiac disorders0/2531/248
Atrial flutterCardiac disorders0/2531/248
Bundle branch block leftCardiac disorders0/2531/248
VertigoEar and labyrinth disorders0/2531/248
Anal fistulaGastrointestinal disorders0/2531/248
Lobar pneumoniaInfections and infestations0/2531/248
Most frequent other events
Most frequent other events
EventExenatide ArmBiphasic Insulin Aspart Arm
HypoglycemiaMetabolism and nutrition disorders134/253128/248
NauseaGastrointestinal disorders84/2531/248
VomitingGastrointestinal disorders38/2538/248
NasopharyngitisInfections and infestations28/25324/248
DiarrheaGastrointestinal disorders24/2535/248
InfluenzaInfections and infestations18/25316/248
HeadacheNervous system disorders12/25313/248

Baseline characteristics

IIT population

Age, Categorical
Age, Categorical(Participants)Exenatide ArmBiphasic Insulin Aspart ArmTotal
<=18 years000
Between 18 and 65 years184174358
>=65 years6974143
Age, Continuous
Age, Continuous(years)Exenatide ArmBiphasic Insulin Aspart ArmTotal
Mean58.8 ± 8.758.5 ± 9.258.7 ± 9.0
Sex: Female, Male
Sex: Female, Male(Participants)Exenatide ArmBiphasic Insulin Aspart ArmTotal
Female135122257
Male118126244
08

Study locations

69 sites
  • Clinical Hospital Osijek
    Osijek, 31000, Croatia
  • Klinica bolnica Dubrava
    Zagreb, 10000, Croatia
  • Klinicki bolnicki centar Zagreb-Rebro
    Zagreb, 10000, Croatia
  • Opca bolnica "Sveti Duh"
    Zagreb, 10000, Croatia
  • Internistische Gemeinschaftspraxis
    Augsburg, 86150, Germany
  • Dr. Karlheinz Hehemann
    Beckum, 59269, Germany
  • Dr. Klaus Busch
    Dortmund, 44137, Germany
  • Medical Clinic and Policlinic 3
    Giessen, 35392, Germany
  • Diabetologische Schwerpunktpraxis
    Hamburg, 21073, Germany
  • IKFE GmbH
    Mainz, 55119, Germany
  • Institut for diabetic research
    Munich, 80804, Germany
  • Profil, Institut fur Stoffwechselstorungen
    Neuss, 41460, Germany
  • Dr. Thomas Behnke
    Neuwied, 56564, Germany
  • Dr. Bernd Donaubauer
    Oschatz, 04758, Germany
  • Marienhospital Osnabruck
    Osnabruck, 49074, Germany
  • Dr. Joerg Steindorf
    Schkeuditz, 04435, Germany
  • Dr. Jerzi Jasinski
    Wiesbaden, 65183, Germany
  • "Polyclinic" General Hospital of Athens
    Athens, 10552, Greece
  • Department of Endocrinology
    Athens, 10676, Greece
  • Diabetes Center
    Athens, 11527, Greece
  • University Hospital of Patras
    Patras, 26500, Greece
  • 1st Internal Medicine Department "Papagergiou"
    Thessaloniki, 56429, Greece
  • Instituto di Endocrinologia
    Catania, 95124, Italy
  • Dipartimento di fisiopatologia clinica
    Florence, 50134, Italy
  • U.O. Medicina Generale
    Milan, 60-20132, Italy
  • Ospedale Civile di Padova
    Padova, 35128, Italy
  • Policlinico Univarsitario P. Giaccone
    Palermo, 90127, Italy
  • U.O. Universita di Malattie del Metabolismo e Diabetologia
    Torino, Italy
  • Gelre Ziekenhuizen
    Apeldoorn, 7300 DS, Netherlands
  • Rijnstate Ziekenhuis
    Arnhem, 6815 AD, Netherlands
  • Maxima Medisch Centrum Location Eindhoven
    Eindhoven, 5631 BM, Netherlands
  • Hospitais da Universidade de Coimbra
    Coimbra, 3000-076, Portugal
  • Hospital de Santo Andre
    Leiria, 2410-197, Portugal
  • Associacao Protectora dos Diabeticos de Portugal
    Lisboa, 1250-203, Portugal
  • Hospital Pedro Hispano
    Matosinhos, 4454-509, Portugal
  • Spitalul Judetean Brasov
    Brasov, 500326, Romania
  • Institutul de Diabet
    Bucuresti, 020475, Romania
  • Spitalul Clinic nr. 1 Judetean
    Judet Timis, 300723, Romania
  • National Endocrinology Research Center
    Moscow, 117036, Russian Federation
  • Setchenov Moscow Medical Academy
    Moscow, 119881, Russian Federation
  • Moscow State Medical Stomatological
    Moscow, 123448, Russian Federation
  • Russian Medical Academy for Advanced Medical Studies, Ministry of Health
    Moscow, 125315, Russian Federation
  • Hospital of St. Elizabeth's
    St. Petersburg, 193257, Russian Federation
  • City Clinical Hospital #2
    St. Petersburg, 194354, Russian Federation
  • Medical Military Academy
    St. Petersburg, 198013, Russian Federation
  • Univerzitetni klinicni center Ljubljana
    Ljubljana, 1000, Slovenia
  • Splosna bolnisnica Maribor
    Maribor, 2000, Slovenia
  • Hospital Vega Baja
    Alicante, 03300, Spain
  • Hospital Clinic i Provincial de Barcelona
    Barcelona, 08036, Spain
  • Endocrinology Service (Planta Baja)
    Palma de Mallorca, 07198, Spain
  • Hospital Virgen de Valme
    Sevilla, 41014, Spain
  • Hospital General de Teruel
    Teruel, 44002, Spain
  • Hospital la Ribera Alzira
    Valencia, 46600 Alzira, Spain
  • Changhua Christian Hospital
    Changhua, 500, Taiwan
  • Tzu Chi General Hospital
    Hualien, Taiwan
  • Veteran General Hospital-Taichung
    Taichung, 407, Taiwan
  • Tri-Service General Hospital
    Taipei, Taiwan
  • Diabetes Research, Ward 34, Birmingham Heartlands Hospital
    Birmingham, B9 5SS, United Kingdom
  • Diabetes Unit, Blackburn Royal Infirmary
    Blackburn, BB2 3LR, United Kingdom
  • Colchester General Hospital
    Colchester, CO4 5JL, United Kingdom
  • Royal Infirmary of Edinburgh
    Edinburgh, EH3 9YW, United Kingdom
  • Glasgow Royal Infirmary
    Glasgow, G4 0SF, United Kingdom
  • The Michael White Center for Diabetes and Endocrinology
    Hull, HU3 2JZ, United Kingdom
  • Clinical Sciences Centre
    Liverpool, L7 8XP, United Kingdom
  • Education Centre, James Cook University Hospital
    Middlesbrough, TS4 3BW, United Kingdom
  • Wellcome Labs, Royal Victoria Infirmary
    Newcastle upon Tyne, NE1 4LP, United Kingdom
  • Queens Medical Centre
    Nottingham, NG7 2UH, United Kingdom
  • Diabetes Trial Unit OCDEM, Churchill Hospital
    Oxford, OX3 7LJ, United Kingdom
  • Diabetes Unit, Gladsone Centre, Maelor Hospital
    Wrexham, LL13 7TD, United Kingdom
09

References and documents

Publications

  • Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia. 2007 Feb;50(2):259-67. doi: 10.1007/s00125-006-0510-2. Epub 2006 Dec 8. PubMed 17160407 ↗
  • Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567. PubMed 22913891 ↗
  • Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10. PubMed 22236356 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 7, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00082407
Lead sponsor
AstraZeneca
Collaborators
Eli Lilly and Company
Responsible party
Sponsor
First posted
May 10, 2004
Start date
Nov 2003
Primary completion
Jul 2008
Completion
Jul 2008
Results posted
Jul 31, 2013
Last update
Apr 7, 2015

Study contacts

Chief Medical Officer, MD
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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