- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02981069
Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM
June 28, 2023 updated by: The University of Texas Health Science Center at San Antonio
Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in Type 2 Diabetes Mellitus (T2DM)
In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous glucose production) and plasma glucose concentration in diabetic subjects.
Researchers will examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This study will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose concentration compared to each agent alone.
Study Type
Interventional
Enrollment (Actual)
90
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Texas
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San Antonio, Texas, United States, 78229
- University of Texas Health Science Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- BMI = 25-35 kg/m^2
- must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or sulfonylurea
- HbA1c >7.0% and <10.0%
- Other than diabetes, subjects must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis.
- Only subjects whose body weight has been stable (± 3 lbs) over the preceding three months and who do not participate in an excessively heavy exercise program will be included.
Exclusion Criteria:
- Presence of significant systemic disease, heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, urosepsis and pyelonephritis, genital mycotic infections, or Type 1 diabetes mellitus
- Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
- Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women or ≥1.5 mg/dl for men, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
- Uncontrolled thyroid disease , Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia
- Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dl), uncontrolled increased LDL-C
- Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
- Use of anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, , GnRH agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finesteride, spironolactone, flutamide) stopped for at least 4 weeks
- Prior history of a malignant disease requiring chemotherapy, prior history of bladder cancer regardless treatment
- Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
- History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
- Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions
- Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)
- Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 8 weeks.
- Eating disorders (anorexia, bulimia) or gastrointestinal disorders
- Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months
- Active history of illicit substance abuse or significant intake of alcohol
- Having a history of bariatric surgery
- Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
- Debilitating uncontrolled psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
- Inability or refusal to comply with protocol
- Current participation or participation in an experimental drug study in previous three months
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Byetta / Bydureon
Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc |
Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
Other Names:
|
Active Comparator: Dapagliflozin
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
|
10mg
Other Names:
|
Active Comparator: Byetta/Bydureon plus Dapagliflozin
Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg |
Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
Other Names:
10mg
Other Names:
|
Placebo Comparator: Placebo
Placebo group (4 weeks and 12 weeks)
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Placebo for Dapagliflozin
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment
Time Frame: ACUTE [after a single dose of each study drug or placebo]
|
After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose.
The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM).
After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg + exenatide 5 ug [ACUTE STUDY].
|
ACUTE [after a single dose of each study drug or placebo]
|
Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.
Time Frame: 16 weeks
|
After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose.
The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM).
After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug.
Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period.
Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination.
Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective "acute" studies.
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Fasting Plasma Glucose (FPG) Concentration
Time Frame: 16 weeks
|
The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure.
Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic.
Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
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16 weeks
|
Change in Plasma Glucagon Concentration
Time Frame: Baseline to 16 weeks
|
Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline.
Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic.
Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
|
Baseline to 16 weeks
|
Change in Plasma Insulin Concentration
Time Frame: Baseline to 16 weeks
|
Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s).
Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic.
Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.
|
Baseline to 16 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Eugenio Cersosimo, MD,PhD, The University of Texas Health Science Center at San Antonio
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 15, 2017
Primary Completion (Actual)
July 14, 2022
Study Completion (Actual)
March 19, 2023
Study Registration Dates
First Submitted
November 30, 2016
First Submitted That Met QC Criteria
November 30, 2016
First Posted (Estimated)
December 2, 2016
Study Record Updates
Last Update Posted (Actual)
July 20, 2023
Last Update Submitted That Met QC Criteria
June 28, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Hyperinsulinism
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Insulin Resistance
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Obesity Agents
- Incretins
- Sodium-Glucose Transporter 2 Inhibitors
- Dapagliflozin
- Exenatide
Other Study ID Numbers
- HSC20160597H
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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