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SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

Primary Purpose

Type II Diabetes Mellitus

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Dapagliflozin

Placebo

About this trial

This is an interventional treatment trial for Type II Diabetes Mellitus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

T2DM subjects
18 - 70 yrs old
BMI = 25-45 kg/m2
Must be on a stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea
HbA1c <10.0%
Stable body weight (± 3 lbs) over preceding 3 months
Do not participate in excessively heavy exercise

Exclusion Criteria:

Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)
Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg

Sites / Locations

University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dapagliflozin

Placebo

Arm Description

20 subjects will receive dapagliflozin 10mg

10 subjects will receive placebo

Outcomes

Primary Outcome Measures

Change in Plasma Glucose Concentration

Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration

Change in Endogenous Glucose Production (EGP)

The change in endogenous glucose production is measured from baseline until the last hour of the study

Secondary Outcome Measures

Change in Plasma Insulin During Measurement of EGP

Measurement of change in plasma insulin concentration during measurement of of EGP from baseline to last hour of the study

Change in Glucagon During EGP Measurement

Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study

Full Information

NCT ID

NCT02592421

First Posted

October 14, 2015

Last Updated

September 15, 2020

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT02592421

Brief Title

SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

Official Title

Protocol 2: Elucidation of Mechanisms Responsible for the Increase in EGP Following SGLT2 Inhibition: Decrease in Plasma Glucose Conc or Change in Islet Hormone (Glucagon/Insulin) Secretion

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

October 23, 2015 (Actual)

Primary Completion Date

October 1, 2018 (Actual)

Study Completion Date

October 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In Protocol 2, the investigators will determine the role of pancreatic hormones (increase in plasma glucagon and decrease in plasma insulin concentration) in the stimulation of EGP following SGLT2 inhibition.

Detailed Description

The inhibition of the renal (kidney) SGLT2 transporter has proven to be an effective therapeutic intervention to reduce plasma glucose levels (amount of glucose found in the liquid part of blood) and HbA1c. In this study, the investigators hope to define the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration. The investigators will examine whether the signal for the increase in EGP (endogenous glucose production) caused by glucosuria (an excess of sugar in the urine, typically associated with diabetes) is mediated via the decrease in plasma glucose and insulin concentrations, or by the increase in plasma glucagon concentration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type II Diabetes Mellitus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dapagliflozin

Arm Type

Active Comparator

Arm Description

20 subjects will receive dapagliflozin 10mg

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

10 subjects will receive placebo

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin

Other Intervention Name(s)

Farxiga

Intervention Description

SGLT2 inhibitor (dapagliflozin)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo Comparator

Primary Outcome Measure Information:

Title

Change in Plasma Glucose Concentration

Description

Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration

Time Frame

Baseline to 240-300 minutes

Title

Change in Endogenous Glucose Production (EGP)

Description

The change in endogenous glucose production is measured from baseline until the last hour of the study

Time Frame

Baseline to 240-300 minutes

Secondary Outcome Measure Information:

Title

Change in Plasma Insulin During Measurement of EGP

Description

Measurement of change in plasma insulin concentration during measurement of of EGP from baseline to last hour of the study

Time Frame

Baseline to 240-300 minutes

Title

Change in Glucagon During EGP Measurement

Description

Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study

Time Frame

Baseline to 240-300 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: T2DM subjects 18 - 70 yrs old BMI = 25-45 kg/m2 Must be on a stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea HbA1c <10.0% Stable body weight (± 3 lbs) over preceding 3 months Do not participate in excessively heavy exercise Exclusion Criteria: Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea) Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ralph A. DeFronzo, MD

Organizational Affiliation

The University of Texas Health Science Center at San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31915153

Citation

Alatrach M, Laichuthai N, Martinez R, Agyin C, Ali AM, Al-Jobori H, Lavynenko O, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors. Diabetes. 2020 Apr;69(4):681-688. doi: 10.2337/db19-0770. Epub 2020 Jan 8.

Results Reference

derived

Learn more about this trial

SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

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