SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

Phase 3

Completed

• Conditions: Type II Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT02592421
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

Study Timeline

• Study First Submitted: 2015-10-14
• Study Start: 2015-10-23
• Study First Submitted QC: 2015-10-28
• Study First Posted: 2015-10-30
• Primary Completion: 2018-10-01
• Study Completion: 2019-10-31
• Results First Submitted: 2019-11-13
• Results First Submitted QC: 2019-12-02
• Results First Posted: 2019-12-18
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-15
• Last Update Posted: 2020-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	10 subjects will receive placebo
Dapagliflozin	Dapagliflozin	20 subjects will receive dapagliflozin 10mg

Primary Outcome Measures

Name	Time	Method
Change in Plasma Glucose Concentration	Baseline to 240-300 minutes	Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration
Change in Endogenous Glucose Production (EGP)	Baseline to 240-300 minutes	The change in endogenous glucose production is measured from baseline until the last hour of the study

Secondary Outcome Measures

Name	Time	Method
Change in Plasma Insulin During Measurement of EGP	Baseline to 240-300 minutes	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	Baseline to 240-300 minutes	Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study

Trial Locations

Locations (1)

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States