SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

Type II Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592421
• Other study ID #: HSC20150668H
• Secondary ID: 5R01DK107680-02
• Status: Completed
• Phase: Phase 3
• Start date: October 23, 2015
• Est. completion date: October 31, 2019

Study information

• Verified date: September 2020
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 31, 2019
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type II Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin
SGLT2 inhibitor (dapagliflozin)
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Plasma Glucose Concentration	Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration	Baseline to 240-300 minutes
Primary	Change in Endogenous Glucose Production (EGP)	The change in endogenous glucose production is measured from baseline until the last hour of the study	Baseline to 240-300 minutes
Secondary	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	Baseline to 240-300 minutes
Secondary	Change in Glucagon During EGP Measurement	Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study	Baseline to 240-300 minutes