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

NCT02981069 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: HSC20160597H
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• 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 \[ACUTE STUDY\].

  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.

  16 weeks

Secondary Outcomes (3)

• Change in Fasting Plasma Glucose (FPG) Concentration

  16 weeks

• Change in Plasma Glucagon Concentration

  Baseline to 16 weeks

• Change in Plasma Insulin Concentration

  Baseline to 16 weeks

Study Arms (4)

Byetta / Bydureon

ACTIVE COMPARATOR

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

Drug: Exenatide

Dapagliflozin

ACTIVE COMPARATOR

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

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

Drug: Dapagliflozin; Drug: Exenatide

Placebo

PLACEBO COMPARATOR

Placebo group (4 weeks and 12 weeks)

Drug: Placebo

Interventions

Dapagliflozin DRUG

10mg

Also known as: Farxiga

Byetta/Bydureon plus Dapagliflozin; Dapagliflozin

Exenatide DRUG

Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)

Also known as: Byetta, Bydureon

Byetta / Bydureon; Byetta/Bydureon plus Dapagliflozin

Placebo DRUG

Placebo for Dapagliflozin

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Professor
• Organization: University of Texas Health San Antonio

cersosimo@uthscsa.edu

12103587200

Study Officials

• Eugenio Cersosimo, MD,PhD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 2, 2016
• Study Start: December 15, 2017
• Primary Completion: July 14, 2022
• Study Completion: March 19, 2023
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2023-06

Locations

US (1)