Diabetes Mellitus, Type 2Phase 4NCT02981069
Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM
A Phase 4 study testing Dapagliflozin and Exenatide in people with Diabetes Mellitus, Type 2, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Dapagliflozin and Exenatide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2017to 19 Mar 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center
San Antonio, Texas, 78229
About this study
Official title: 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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Dapagliflozin, Exenatide, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Farxiga
10mg
ExenatideDrug
Also called Byetta, Bydureon
Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
PlaceboDrug
Placebo for Dapagliflozin
| Study group | Role | What they receive |
|---|---|---|
| Byetta / Bydureon | Active comparator | Exenatide:
4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc Receives: Drug: Exenatide |
| Dapagliflozin | Active comparator | 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Receives: Drug: Dapagliflozin |
| Byetta/Bydureon plus Dapagliflozin | Active comparator | 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 Receives: Drug: Dapagliflozin; Drug: Exenatide |
| Placebo | Placebo comparator | Placebo group (4 weeks and 12 weeks) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment
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].
Measured: 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.
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.
Measured: 16 weeks
Secondary outcomes (3)
Change in Fasting Plasma Glucose (FPG) Concentration
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.
Measured: 16 weeks
Change in Plasma Glucagon Concentration
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.
Measured: Baseline to 16 weeks
Change in Plasma Insulin Concentration
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.
Measured: Baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study start15 Dec 2017
- Primary completion14 Jul 2022
- Study completion19 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Eugenio Cersosimo, MD,PhD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981069
- Sponsor's protocol ID
- HSC20160597H
- Status last verified
- Jun 2023
- First submitted
- 30 Nov 2016
- Last updated
- 20 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in Type 2 Diabetes Mellitus (T2DM)
- ClinicalTrials.gov ID
- NCT02981069
- Acronym / sponsor ID
- HSC20160597H
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 14 Jul 2022 (actual)
- Study completion
- 19 Mar 2023 (actual)
- First posted
- 2 Dec 2016 (estimated)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Byetta / Bydureon | Active comparator | Drug: ExenatideExenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc |
| Dapagliflozin | Active comparator | Drug: Dapagliflozin4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg |
| Byetta/Bydureon plus Dapagliflozin | Active comparator | Drug: Dapagliflozin, Drug: ExenatideExenatide: 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 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo group (4 weeks and 12 weeks) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DapagliflozinAlso: Farxiga10mg | Drug | Byetta/Bydureon plus Dapagliflozin, Dapagliflozin |
| ExenatideAlso: Byetta, BydureonByetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly) | Drug | Byetta / Bydureon, Byetta/Bydureon plus Dapagliflozin |
| PlaceboPlacebo for Dapagliflozin | Drug | Placebo |
Primary outcome
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].
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.
3 secondary outcomes
Change in Fasting Plasma Glucose (FPG) Concentration
Time frame: 16 weeks
Change in Plasma Glucagon Concentration
Time frame: Baseline to 16 weeks
Change in Plasma Insulin Concentration
Time frame: Baseline to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugenio Cersosimo, MD,PhD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin and Exenatide in people with Diabetes Mellitus, Type 2, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.