Empagliflozin and Hepatic Glucose Metabolism

The University of Texas System (UT)

Status and phase: Completed; Phase 4

Conditions: Hepatic Glucose Metabolism

Treatments: Drug: Control; Drug: Empagliflozin 25 MG

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03193684

HSC20170214H

2R01DK097554-06 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 2 patient groups, including a placebo group

Treatment

Experimental group

Description:

empagliflozin 25 mg per day

Treatment:

Drug: Empagliflozin 25 MG

control

Placebo Comparator group

Description:

matching placebo 1 pill per day

Treatment:

Drug: Control