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Comparison of the Effect of Exenatide Versus Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione

Phase 4
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT00729326
Lead Sponsor
AstraZeneca
Brief Summary

This study is designed to compare the short-term effects and mechanisms of action of exenatide with those of sitagliptin when either is added to an oral agent(metformin or a thiazolidinedione \[TZD\]) in adult patients with type 2 diabetes mellitus(T2DM) with inadequate glycemic control.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
83
Inclusion Criteria
  • Have type 2 diabetes
  • Has HbA1c 7.0% to 11.0%, at or within 4 weeks prior to Visit 1.
  • Have a fasting glucose concentration <280 mg/dL at Visit 1
  • Have been treated with a stable dose of immediate or extended release metformin for at least 60 days prior to screening OR TZD (rosiglitazone or pioglitazone) for at least 120 days prior to screening.
  • Are between 18 and 70 years of age, inclusive.
  • Have body mass index ≥25 kg/m2 and ≤45 kg/m2.
  • Have a history of stable body weight (not varying by >10% for at least 3 months prior to screening).
  • Can swallow oral study drug capsule, without splitting or crushing.
Exclusion Criteria
  • Female patients of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause) who meet any of the following criteria:

    • Are breastfeeding.
    • Test positive for pregnancy at the time of screening.
    • Intend to become pregnant during the study.
    • Have not practiced a reliable method of birth control (for example, use of oral contraceptives or Norplant®; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for 3 months prior to screening.
  • Treated with any of the following medications:

    • Insulin, exenatide, pramlintide, sulfonylureas or meglitinides within 3 months of screening
    • Alpha-glucosidase inhibitor within 2 months of screening.
    • Drugs that directly affect gastrointestinal motility, including, but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
    • Use of a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phentermine, or similar over-the-counter medications) within 3 months prior to Visit 1.
    • Systemic corticosteroids by oral, intravenous, or intramuscular route within 2 months of screening.
  • Have a history of renal transplantation or are currently receiving renal dialysis.

  • Have obvious clinical signs or symptoms of liver disease or acute or chronic hepatitis.

  • Have known active proliferative retinopathy or macular edema expected to need treatment with focal photocoagulation within 3 months.

  • Have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.

  • Have had organ transplantation.

  • Have received GLP-1 analogs other than exenatide or DPP-4 inhibitors within the previous 3 months.

  • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Sequence Asitagliptin-
Sequence Bplacebo-
Sequence Bsitagliptin-
Sequence Aplacebo-
Sequence Bexenatide-
Sequence Aexenatide-
Primary Outcome Measures
NameTimeMethod
Change in Time-averaged Glucose During a 24 Hour Periodbaseline and 8 Weeks

Change in time-averaged glucose during a 24-hour period from baseline to endpoint (i.e., time-averaged glucose over 24 hours at endpoint minus time-averaged glucose over 24 hours at baseline).

Secondary Outcome Measures
NameTimeMethod
Change in Two-hour Postprandial Glucose After the Morning Mealbaseline and 8 Weeks

Change in 2 hour post-prandial glucose after the morning meal from baseline to endpoint (i.e., glucose level 2 hours after the morning meal at baseline minus glucose level 2 hours after the morning meal at endpoint)

Change in Fasting Blood Glucose After the Morning Mealbaseline and 8 Weeks

Change in fasting blood glucose after the morning meal from baseline to endpoint (i.e., fasting blood glucose after the morning meal at baseline minus fasting blood glucose after the morning meal at endpoint)

Change in Postprandial Glucagon Area Under the Concentration-time Curve (AUC) After the Morning Mealbaseline and 8 Weeks

Change in Postprandial Glucagon AUC after the morning meal (t=0 to 4 hours) (i.e., Glucagon AUC over the first 4 hours following the morning meal at baseline minus glucagon AUC over the first 4 hours following the morning meal at endpoint)

Change in Postprandial Glucagon AUC Excursion After the Morning Mealbaseline and 8 Weeks

Change in postprandial glucagon AUC excursion after the morning meal (t=0 to 4 hours) (i.e., glucagon AUC excursion for 4 hours following the morning meal at baseline minus glucagon AUC excursion for 4 hours following the morning meal at endpoint)

Change in Postprandial Triglyceride AUC After the Morning Mealbaseline and 8 Weeks

Change in postprandial triglyceride AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC after the morning meal at baseline minus postprandial triglyceride AUC after the morning meal at endpoint)

Change in Postprandial Triglyceride AUC Excursion After the Morning Mealbaseline and 8 Weeks

Change in postprandial triglyceride AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC excursion after the morning meal at baseline minus postprandial triglyceride AUC excursion after the morning meal at endpoint)

Change in Postprandial C-peptide AUC After the Morning Mealbaseline and 8 Weeks

Change in postprandial C-peptide AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC after the morning meal at baseline minus postprandial C-peptide AUC after the morning meal at endpoint)

Change in Postprandial C-peptide AUC Excursion After the Morning Mealbaseline and 8 Weeks

Change in Postprandial C-peptide AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC excursion after the morning meal at baseline minus postprandial C-peptide AUC excursion after the morning meal at endpoint)

Change in Postprandial Insulin AUC After the Morning Mealbaseline and 8 Weeks

Change in postprandial insulin AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC after the morning meal at baseline minus postprandial insulin AUC after the morning meal at endpoint)

Change in Postprandial Insulin AUC Excursion After the Morning Mealbaseline and 8 Weeks

Change in Postprandial insulin AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC excursion after the morning meal at baseline minus postprandial insulin AUC excursion after the morning meal at endpoint)

Change in Postprandial Active GLP-1 AUC After the Morning Mealbaseline and 8 Weeks

Change in Postprandial active GLP-1 AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC after the morning meal at baseline minus postprandial active GLP-1 AUC after the morning meal at endpoint)

Change in Postprandial Active GLP-1 AUC Excursion After the Monrning Mealbaseline and 8 Weeks

Change in Postprandial active GLP-1 AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC excursion after the morning meal at baseline minus postprandial active GLP-1 AUC excursion after the morning meals at endpoint)

Percentage of Patients Experiencing Hypoglycemia (Baseline to Week 4)4 Weeks

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose \<54mg/dL

Episodes of Hypoglycemia (Baseline to Week 4)4 weeks

Number of episodes of hypoglycemia experienced during the first 4 weeks of the study

Percentage of Patients Experiencing Hypoglycemia (Week 4 to Week 8)8 weeks

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose \<54mg/dL

Episodes of Hypoglycemia (Week 4 to Week 8)8 weeks

Number of episodes of hypoglycemia experienced between week 4 and week 8 of the study

Percentage of Patients Experiencing Hypoglycemia (Overall)4 weeks and 8 weeks

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose \<54mg/dL

Episodes of Hypoglycemia (Overall)4 weeks and 8 weeks

Number of episodes of hypoglycemia experienced overall during the study

Trial Locations

Locations (1)

Research Site

🇺🇸

San Antonio, Texas, United States

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