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Trial · Interventional

CompletedPhase 4Results postedRegistry data

Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM

Overview

Status
Completed
Phase
Phase 4
Enrollment
90 participants (actual)
Sponsor
The University of Texas Health Science Center at San Antonio · Other
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
15 Dec 2017
Primary completion
14 Jul 2022
Completion
19 Mar 2023
First posted
2 Dec 2016 (estimated)
Last update posted
20 Jul 2023
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2018202020222024
  1. Ph 4

    Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM

    NCT02981069

    15 Dec 2017 to 19 Mar 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • DapagliflozinDrug
  • ExenatideDrug
  • PlaceboDrug

Arms4

  • Active comparator

    Byetta / Bydureon

    Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc

  • Active comparator

    Dapagliflozin

    4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg

  • 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

  • Placebo comparator

    Placebo

    Placebo group (4 weeks and 12 weeks)

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. 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]

    Registry description

    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 \[ACUTE STUDY\].

  2. Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.

    Time frame · 16 weeks

    Registry description

    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.

Secondary outcomes(3)
  1. Change in Fasting Plasma Glucose (FPG) Concentration

    Time frame · 16 weeks

    Registry description

    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.

  2. Change in Plasma Glucagon Concentration

    Time frame · Baseline to 16 weeks

    Registry description

    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.

  3. Change in Plasma Insulin Concentration

    Time frame · Baseline to 16 weeks

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· ACUTE [after a single dose of each study drug or placebo]

Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment

GroupValue (mg/kg.min)Spread
EXENATIDE-0.180.02
Dapagliflozin0.140.03
Exenatide Plus Dapagliflozin-0.080.03
Placebo-0.030.02
Primary outcomeMean· 16 weeks

Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.

GroupValue (mg/kg.min)Spread
EXENATIDE-0.230.02
Dapagliflozin0.200.03
Exenatide Plus Dapagliflozin-0.120.03
Secondary and other outcome results(3)
Secondary outcomeMean· 16 weeks

Change in Fasting Plasma Glucose (FPG) Concentration

GroupValue (mg/dl)Spread
Byetta / Bydureon421
Dapagliflozin723
Byetta/Bydureon Plus Dapagliflozin113
Secondary outcomeMean· Baseline to 16 weeks

Change in Plasma Glucagon Concentration

GroupValue (pg/ml)Spread
Dapa+Exe42
Dapa52
Exenatide-62
Secondary outcomeMean· Baseline to 16 weeks

Change in Plasma Insulin Concentration

GroupValue (microUnits/ml)Spread
Dapa+Exe-21
Dapa-22
Exenatide32

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Byetta / BydureonExenatide: 4 weeks of exenatide 5 mcg twice daily followed by Bydureon 2mg sc weekly Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)0 / 250 / 256 / 25
Dapagliflozin16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg0 / 250 / 254 / 25
Byetta/Bydureon Plus DapagliflozinExenatide: 4 weeks of exenatide followed by 12 weeks of Bydureon 2mg sc once weekly PLUS Dapagliflozin: 16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)0 / 250 / 257 / 25
Placebo16 weeks of placebo administration0 / 150 / 150 / 15

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 70 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. BMI = 25-35 kg/m\^2 2. must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or sulfonylurea 3. HbA1c \>7.0% and \<10.0% 4. 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. 5. 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: 1. 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 2. 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 3. 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. 4. Uncontrolled thyroid disease , Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia 5. Significantly elevated triglyceride levels (fasting triglyceride \> 400 mg/dl), uncontrolled increased LDL-C 6. Untreated or poorly controlled hypertension (sitting blood pressure \> 160/95 mm Hg) 7. 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 8. Prior history of a malignant disease requiring chemotherapy, prior history of bladder cancer regardless treatment 9. 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 10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit. 11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions 12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide) 13. Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 8 weeks. 14. Eating disorders (anorexia, bulimia) or gastrointestinal disorders 15. Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months 16. Active history of illicit substance abuse or significant intake of alcohol 17. Having a history of bariatric surgery 18. Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD) 19. Debilitating uncontrolled psychiatric disorder such as psychosis or neurological condition that might confound outcome variables 20. Inability or refusal to comply with protocol 21. Current participation or participation in an experimental drug study in previous three months

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