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

Sponsor
Medical University of Vienna
Study ID
NCT02558270
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Accepted

Interventions

Study Details

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.

Key Dates

Start date
Jun 30, 2016
Status verified
Sep 2016
Primary completion
Dec 31, 2017
Completion
Jun 30, 2018

Study Design

Enrollment
20 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Active Comparator: patients dapa
    Patients will be administered Dapagliflozin 10mg
  • Placebo Comparator: patients placebo
    Patients will be administered a placebo
  • Active Comparator: controls dapa
    controls will be administered Dapagliflozin 10mg
  • Placebo Comparator: controls placebo
    controls will be administered a placebo

Primary Outcome Measure

Change in endogenous glucose production [ Time Frame: 420 minutes ]

Central Contacts

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