Empagliflozin and Hepatic Glucose Metabolism

Hepatic Glucose Metabolism Clinical Trial

Official title:

Effect of Empagliflozin on Hepatic Glucose Metabolism: Role of Autonomic Nervous System

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03193684
• Other study ID #: HSC20170214H
• Secondary ID: 2R01DK097554-06
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: May 20, 2018
• Est. completion date: January 2024

Study information

• Verified date: February 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake

Description:

Purpose/Objectives: To investigate the effect of empagliflozin, an SGLT2 inhibitor on hepatic glucose production and the role of autonomic nervous system in mediating the increase in hepatic glucose production in response glucosuria Research Design/Plan: the role of autonomic nervous system in the increase in hepatic glucose production caused by empagliflozin will be examined with norepinephrine (NE) turnover in two protocols. The first protocol is cross sectional, in which 36 T2DM patients will receive hepatic glucose production (HGP) and NE turnover will be measured before and after empagliflozin or placebo administration. In protocol 2, diabetic and non-diabetic subjects will receive baseline HGP, NE turnover, hepatic glucose uptake (HGU) and liver fat measurement before at 2 days after the start and 12 weeks after empagliflozin or placebo treatment.

Methods: the following techniques will be employed (1) Measurement of hepatic glucose production with 3H-glucose infusion, with and without glucose clamp, (2) substrate oxidation with indirect calorimetry and plasma ketone/lactate/insulin/glucagon concentrations; (3) Measurement of HGU with Oral-IV double tracer infusion; (4) Measurement of whole body norepinephrine turnover with 3H-norepinephrine infusion; (5) Measurement of heart rate variability; (6) Measurement of liver fat content with 1H-MRS Clinical Relevance: The results of the present studies will help identify the mechanism responsible for the increase in HGP caused by empagliflozin and the increase in ketone production. The first action of the drug ameliorates its clinical efficacy while the second increases the risk of adverse events (ketoacidosis). Identifying the mechanisms underlying these actions will help developing therapeutic strategies which increase the drug clinical efficacy and mitigates its adverse events.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: January 2024
• Est. primary completion date: January 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• eGFR>60 ml/min healthy volunteers type 2 diabetes patients who otherwise healthy

Exclusion Criteria:

• eGFR <60 T2DM patients on insulin, GLP-1 RA or SGLT2 treatment Major organ disease type 1 diabetes

Related Conditions & MeSH terms

• Hepatic Glucose Metabolism

Intervention

Drug:
• Empagliflozin 25 MG
subjects will receive daily dose of 25mg of empagliflozin for 3 months
• Control
Placebo

Locations

Country	Name	City	State
United States	Diabetes Division, UTHSCSA	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
Other	hepatic fat content	the effect of treatment on hepatic fat content will be measured with MRS	12 weeks
Primary	effect of empagliflozin on autonomic nervous system	autonomic activity will be measured with as NE turnover rate	12 weeks
Secondary	hepatic glucose production and uptake	HGP and HGU will be measured with tracer dilution technique	12 weeks