Empagliflozin and Hepatic Glucose Metabolism

NCT ID: NCT03193684

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-20
• Study Completion Date: 2024-01-30

Brief 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

Detailed 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.

Conditions

Hepatic Glucose Metabolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Treatment

empagliflozin 25 mg per day

Group Type: EXPERIMENTAL

Empagliflozin 25 MG

Intervention Type: DRUG

subjects will receive daily dose of 25mg of empagliflozin for 3 months

control

matching placebo 1 pill per day

Group Type: PLACEBO_COMPARATOR

Control

Intervention Type: DRUG

Placebo

Interventions

Empagliflozin 25 MG

subjects will receive daily dose of 25mg of empagliflozin for 3 months

Intervention Type: DRUG

Control

Placebo

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Muhammad Abdul-Ghani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Diabetes Division, UTHSCSA

Locations

Diabetes Division, UTHSCSA

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2R01DK097554-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC20170214H

Identifier Type: -

Identifier Source: org_study_id