SGLTi, Hepatic Glucose Production and Ketogenesis
ConditionType 2 Diabetes
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age30-75
SponsorThe University of Texas Health Science Center at San Antonio
About this trial
In this study, we will test the hypothesis that distinct mechanisms account for the SGLT2i-induced stimulation of ketogenesis and lipolysis versus endogenous (hepatic) glucose production in patients with type 2 diabetes (T2D) and type 1 diabetes (T1D), and that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. We will conduct five distinct experiments to test this hypothesis in patients with T2D and T1D.
MAIN STUDY: To examine the effect of empagliflozin versus empagliflozin/pancreatic clamp on EGP (6,6, D2-glucose), gluconeogenesis (D2O), lipolysis (U-2H-glycerol), ketogenesis (13C-palmitate conversion to 3-betahydroxybuyrate), and norepinephrine turnover (3H-NE) in type 2 diabetes subjects.
Eligibility criteria
Qualifiers
Ages 30-75
BMI (Body Mass Index) 21-45 kg/m2
HbA1c = 7.0-11%
eGFR (estimated glomerular filtration rate)> 60 ml/min/1.73m2
Disqualifiers
Patients treated with Thiazolidinediones (TZDs), or Insulin are excluded.
Patients taking medications other than Sulfonylureas/Metformin (SU/MET), stable dose of GLP1-RA and DPP4i known to affect glucose metabolism are excluded. Patients taking SGLT2i within 2 months of screening visit will be excluded from participating in this study, however they may be asked whether they would agree to discontinue the medication for two months to become eligible. (Please see clarification below.) *
Subjects with evidence of proliferative retinopathy or estimated glomerular filtration rate (eGFR) < 60 are excluded
Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices * Only participants who are taking SGLT2 inhibitors during the prescreening period will be asked to discontinue the medication at least two months prior to the screening visit. If they agree, they will return for an HbA1c measurement four weeks after stopping the SGLT2 inhibitor.
Trial design
Treatments tested in this trial
- Empagliflozin 25 MG
- Placebo
Treatment groups
30 Participants
are divided into 2 treatment groupsSponsors and collaborators
The University of Texas Health Science Center at San Antonio
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov