Effects of SGLT-2 Inhibition on Hepatic Glucose and Energy Metabolism

Phase 2

• Conditions: Type 2 Diabetes; Metabolically Healthy Controls
• Interventions: Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT02558270
• Lead Sponsor: Medical University of Vienna

Brief Summary

Inhibition of SGLT2 by specific inhibitors has been shown to reduce the renal threshold for glucose excretion in patients with type 2 diabetes mellitus (T2DM) and control subjects leading to significant renal glucose loss even in the presence of normal glucose concentrations. SGLT2 inhibition with canagliflozin induces a 24h urinary glucose loss of around 70g in healthy subjects.

Recent studies indicate that under fasting and postprandial conditions administration of SGLT-2 inhibitors leads to increase in endogenous (hepatic) glucose production (EGP) potentially counteracting the glucose lowering potency of these drugs. Dapagliflozin has been shown to acutely increase endogenous glucose production (EGP) and plasma glucagon concentrations under postabsorptive conditions within 2 hours after drug ingestion in patients with (T2DM). Glucagon binds to receptors in the liver and activates hepatic gluconeogenesis (GNG) and glycogenolysis, likely contributing to the observed increase in EGP.

So far the likely interrelation between acute changes in hepatic glucose metabolism and energy turnover contributing to increased hepatic glucose production induced by SGLT2 inhibition has not been studied. It is known that out of the 80% of oxygen consumption coupled to ATP synthesis, 7- 10% is used by GNG. However, so far the effects of dapagliflozin on acute changes in gluconeogenesis (GNG) and ATP turnover in hepatic tissue and on the time course of hormones involved in hypoglycaemia counter regulation have not been studied.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-09-22
• Study First Submitted QC: 2015-09-22
• Study First Posted: 2015-09-23
• Study Start: 2016-06
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-26
• Last Update Posted: 2016-09-27
• Primary Completion: 2017-12
• Study Completion: 2018-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
controls placebo	Placebo	controls will be administered a placebo
patients placebo	Placebo	Patients will be administered a placebo
controls dapa	Dapagliflozin	controls will be administered Dapagliflozin 10mg
patients dapa	Dapagliflozin	Patients will be administered Dapagliflozin 10mg

Primary Outcome Measures

Name	Time	Method
Change in endogenous glucose production	420 minutes

Secondary Outcome Measures

Name	Time	Method
Change in hepatic gluconeogenesis	420 minutes
Change in hepatic lipid content	420 minutes
Change in hepatic glycogen content	420 minutes
Changes in hormones involved in hypoglycemia counter regulation	420 minutes
Changes in hepatic ATP concentrations	420 minutes

Trial Locations

Locations (1)

Medical University Of Vienna, Department of Internal Medicine III; 🇦🇹 Vienna, Austria