Diabetes Mellitus, Type 2Phase 4NCT03331289
Can Exenatide Prevent Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria
A Phase 4 study testing Exenatide, Dapagliflozin and Exenatide and Dapagliflozin 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
Research Design/Plan: After screening, each subject will receive 1 measurements of Endogenous Glucose Production [EGP] with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer Oral Glucose Tolerance Test [OGTT]. Methods: Visit 1: Screening. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Exenatide, Dapagliflozin and Exenatide and Dapagliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2018to 4 Nov 2022
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Health Status: Type 2 Diabetes Mellitus according to ADA criteria (subjects must be in good general health as determined by physical exam, medical history, blood chemistry-CBC, TSH, T4, EKG and urinalysis)
- BMI: 21-45kg/m
- HbA1C>7.0% and <10.5%
- Medication: Drug naïve and/or on a stable dose of metformin and/or sulfonylurea (more than 3 months)
Who cannot join
- Health Status: Type 1 Diabetics
- Proliferative diabetic retinopathy
- Plasma Creatinine greater than 1.4mg/dL in females or greater than 1.5mg/dL in males, or 24 hour urine albumin excretion greater than 300mg/dL
- Medication: Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)
Trial locations and contacts
1 site in 1 country.
United States1 site
University Health System Texas Diabetic Institute
San Antonio, Texas, 78207
About this study
Official title: SGLT2 INHIBITION AND STIMULATION OF ENDOGENOUS GLUCOSE PRODUCTION [EGP]: Can the Glucagon-like Peptide-1 [GLP-1] Receptor Agonist, Exenatide, Prevent the Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria
Research Design/Plan: After screening, each subject will receive 1 measurements of Endogenous Glucose Production [EGP] with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer Oral Glucose Tolerance Test [OGTT].
Methods: Visit 1: Screening. Medical history will be obtained, physical exam performed, and pregnancy test performed.
Visit 2: Endogenous Glucose Production Measurement: The rate of EGP will be measured with 3-3H-glucose.
Visit 3: Double Tracer OGTT
Read the detailed description
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 hours (from 6 AM to 2 PM). After a 3-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 plus exenatide 5 ug. Following the test medication at 9 AM, blood samples will be drawn every 15 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations and glucose specific activity will be measured.
Visit 1: Screening. Medical history \& physical exam will be performed. Blood will be drawn for fasting plasma glucose [FPG], routine blood chemistries, complete blood count [CBC], lipid profile, HbA1c, and thyroid function [TSH], Urinalysis, electrocardiogram [EKG], albumin/creatinine ratio and pregnancy test will be performed.
Visit 2: EGP Measurement: The rate of endogenous glucose production will be measured with 3-3H-glucose infusion. [3-3H]-glucose infusion will be started at 6 in the morning [AM] and continued until 2:30 afternoon [PM](5 hours after drug administration). At 6 AM a catheter will be placed into an anticubital vein and a prime (40 uCi x FPG/100)- continuous (0.4 uCi) infusion of [3-3H]- glucose will be started and continued until 2:30 PM. (5 hours after drug administration). Participant's hand will be placed in a box heated to 50-60°C (122-140°F). Baseline blood samples will be obtained at-210, -60, -50, -45, -40, -35, -30, -20, -10, and 0 . After 3.5 hours of tracer equilibration blood samples will be obtained every 10-20 minutes from 9 AM to 2 PM. Plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations, and [3-3H]-glucose specific activity will be measured. Urine will be collected from 6 to 9 AM and from 9 AM to 2 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated. The study will end at 2:30 PM.
Visit 3: Double Tracer Oral Glucose Tolerance Test [OGTT]: Within the week after the measurement of EGP, all subjects will have a 5-hour OGTT with measurement of plasma glucose, insulin (I), C-peptide (CP), and glucagon concentrations at -180, -6-, -5-, -45, -40, -35, -30, -20, -10, 0 and every 15-30 minutes thereafter to obtain a measure of overall glucose tolerance, insulin secretion (CP0-120/G0-120), insulin sensitivity ([Matsuda Index=MI]), beta cell function, (CP0-120/G0-120 x MI), and suppression of plasma glucagon concentration (64). At 7 AM a catheter will be placed into an antecubital vein and a prime (25 uCi x FPG/100)- continuous (0.25 uCi) infusion of [3-3H]- glucose will be started and continued until 3 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated.
HbA1c will be measured 2x, 1 on the day of the OGTT \& 1 on the day of the EGP measurement.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Placebo, Exenatide, Dapagliflozin, Exenatide and Dapagliflozin
- 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.
PlaceboDrug
Also called Placebo drug
Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period
ExenatideDrug
Also called Byetta, Bydureon
Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period
DapagliflozinDrug
Also called Farxiga
Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period
Exenatide and DapagliflozinDrug
Also called Byetta plus Dapagliflozin
Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | we 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 conc compared to each agent alone. Receives: Drug: Placebo |
| Exenatide | Active comparator | we 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 conc compared to each agent alone. Receives: Drug: Exenatide |
| Dapagliflozin | Active comparator | we 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 conc compared to each agent alone. Receives: Drug: Dapagliflozin |
| Exenatide and Dapagliflozin | Active comparator | we 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 conc compared to each agent alone. Receives: Drug: Exenatide and Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in EGP From Baseline to Post-oral Glucose Load.
The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 acute drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin this data includes change in EGP above baseline following dapagliflozin alone vs dapagliflozin/exenatide) with ANOVA.
Measured: From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start28 Feb 2018
- Primary completion31 Mar 2022
- Study completion4 Nov 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Participants will be randomized to one of four groups (20 per group): i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03331289
- Sponsor's protocol ID
- HSC20170582H
- Other IDs
- R01DK107680
- Status last verified
- Jul 2023
- First submitted
- 31 Oct 2017
- Last updated
- 24 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD, all IPD that underlie results in a publication
Publications
Alatrach M, Agyin C, Solis-Herrera C, Lavryneko O, Adams J, Gastaldelli A, Triplitt C, DeFronzo RA, Cersosimo E. Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care. 2022 Jun 2;45(6):1372-1380. doi: 10.2337/dc21-1798.
PubMed 35235659
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SGLT2 INHIBITION AND STIMULATION OF ENDOGENOUS GLUCOSE PRODUCTION [EGP]: Can the Glucagon-like Peptide-1 [GLP-1] Receptor Agonist, Exenatide, Prevent the Increase in EGP in Response to Dapagliflozin-induced Increase in Glucosuria
- ClinicalTrials.gov ID
- NCT03331289
- Acronym / sponsor ID
- HSC20170582H
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 4 Nov 2022 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 24 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research Design/Plan: After screening, each subject will receive 1 measurements of Endogenous Glucose Production [EGP] with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer Oral Glucose Tolerance Test [OGTT].
Methods: Visit 1: Screening. Medical history will be obtained, physical exam performed, and pregnancy test performed.
Visit 2: Endogenous Glucose Production Measurement: The rate of EGP will be measured with 3-3H-glucose.
Visit 3: Double Tracer OGTT
Detailed description
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 hours (from 6 AM to 2 PM). After a 3-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 plus exenatide 5 ug. Following the test medication at 9 AM, blood samples will be drawn every 15 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations and glucose specific activity will be measured.
Visit 1: Screening. Medical history \& physical exam will be performed. Blood will be drawn for fasting plasma glucose [FPG], routine blood chemistries, complete blood count [CBC], lipid profile, HbA1c, and thyroid function [TSH], Urinalysis, electrocardiogram [EKG], albumin/creatinine ratio and pregnancy test will be performed.
Visit 2: EGP Measurement: The rate of endogenous glucose production will be measured with 3-3H-glucose infusion. [3-3H]-glucose infusion will be started at 6 in the morning [AM] and continued until 2:30 afternoon [PM](5 hours after drug administration). At 6 AM a catheter will be placed into an anticubital vein and a prime (40 uCi x FPG/100)- continuous (0.4 uCi) infusion of [3-3H]- glucose will be started and continued until 2:30 PM. (5 hours after drug administration). Participant's hand will be placed in a box heated to 50-60°C (122-140°F). Baseline blood samples will be obtained at-210, -60, -50, -45, -40, -35, -30, -20, -10, and 0 . After 3.5 hours of tracer equilibration blood samples will be obtained every 10-20 minutes from 9 AM to 2 PM. Plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations, and [3-3H]-glucose specific activity will be measured. Urine will be collected from 6 to 9 AM and from 9 AM to 2 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated. The study will end at 2:30 PM.
Visit 3: Double Tracer Oral Glucose Tolerance Test [OGTT]: Within the week after the measurement of EGP, all subjects will have a 5-hour OGTT with measurement of plasma glucose, insulin (I), C-peptide (CP), and glucagon concentrations at -180, -6-, -5-, -45, -40, -35, -30, -20, -10, 0 and every 15-30 minutes thereafter to obtain a measure of overall glucose tolerance, insulin secretion (CP0-120/G0-120), insulin sensitivity ([Matsuda Index=MI]), beta cell function, (CP0-120/G0-120 x MI), and suppression of plasma glucagon concentration (64). At 7 AM a catheter will be placed into an antecubital vein and a prime (25 uCi x FPG/100)- continuous (0.25 uCi) infusion of [3-3H]- glucose will be started and continued until 3 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated.
HbA1c will be measured 2x, 1 on the day of the OGTT \& 1 on the day of the EGP measurement.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Participants will be randomized to one of four groups (20 per group): i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebowe 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 conc compared to each agent alone. |
| Exenatide | Active comparator | Drug: Exenatidewe 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 conc compared to each agent alone. |
| Dapagliflozin | Active comparator | Drug: Dapagliflozinwe 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 conc compared to each agent alone. |
| Exenatide and Dapagliflozin | Active comparator | Drug: Exenatide and Dapagliflozinwe 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 conc compared to each agent alone. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Health Status: Type 2 Diabetes Mellitus according to ADA criteria (subjects must be in good general health as determined by physical exam, medical history, blood chemistry-CBC, TSH, T4, EKG and urinalysis)
- BMI: 21-45kg/m
- HbA1C>7.0% and <10.5%
- Medication: Drug naïve and/or on a stable dose of metformin and/or sulfonylurea (more than 3 months)
Key exclusion criteria (4 listed)
- Health Status: Type 1 Diabetics
- Proliferative diabetic retinopathy
- Plasma Creatinine greater than 1.4mg/dL in females or greater than 1.5mg/dL in males, or 24 hour urine albumin excretion greater than 300mg/dL
- Medication: Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)
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 |
|---|---|---|
| PlaceboAlso: Placebo drugPlacebo will be administered to 20 subjects after a 3 hour tracer equilibration period | Drug | Placebo |
| ExenatideAlso: Byetta, BydureonExenatide will be administered to 20 subjects after a 3 hour tracer equilibration period | Drug | Exenatide |
| DapagliflozinAlso: FarxigaDapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period | Drug | Dapagliflozin |
| Exenatide and DapagliflozinAlso: Byetta plus DapagliflozinExenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period | Drug | Exenatide and Dapagliflozin |
Primary outcome
Change in EGP From Baseline to Post-oral Glucose Load.
Time frame: From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes]
The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 acute drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin this data includes change in EGP above baseline following dapagliflozin alone vs dapagliflozin/exenatide) with ANOVA.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35235659Alatrach M, Agyin C, Solis-Herrera C, Lavryneko O, Adams J, Gastaldelli A, Triplitt C, DeFronzo RA, Cersosimo E. Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care. 2022 Jun 2;45(6):1372-1380. doi: 10.2337/dc21-1798.
- Individual participant dataSharing planned: Yes. All collected IPD, all IPD that underlie results in a publication
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Exenatide, Dapagliflozin and Exenatide and Dapagliflozin 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 4 inclusion and 4 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 24 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 24 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 EGP From Baseline to Post-oral Glucose Load. (time frame: From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03331289, which also lists 1 linked publication.
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 24 Jul 2023.