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SGLTi, Hepatic Glucose Production and Ketogenesis

Protocol l: SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
30 Years to 75 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Mentioned in the study description

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Heart tracing (ECG), Physical exams, Infusions

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Participants must be in general good health based on medical history, physical exam, screening blood chemistries, CBC, TSH/T4, EKG, and urinalysis."
  • "In Study 1a, EGP will be measured with a prime-continuous 6,6, D2-glucose infusion and lipolysis will be measured with prime-continuous infusion of U-2H-glycerol."
  • "The rate of ketogenesis will be determined by infusion of 13C palmitate and quantitating the enrichment of 13C in 3-hydroxybutyrate (BHB)."
  • "Total body NE turnover will be measured with 3H-norepinephrine (3H-NE) infusion before and after empagliflozin administration."
Compensation
Mentioned in the study description
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study looks at how SGLT2 diabetes drugs affect sugar made by the liver, fat breakdown, and ketones, which are made from fat. It also tests whether pioglitazone can prevent increases in fat breakdown and ketones. The research includes people with type 1 or type 2 diabetes, but the main study and rules below are for people with type 2 diabetes.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have type 2 diabetes and be 30–75 years old.
  • Have a BMI of 21–45. BMI measures weight compared with height.
  • Have an HbA1c of 7.0–11%. This blood test shows average blood sugar over time.
  • Have an eGFR above 60, a measure of kidney function, and blood pressure no higher than 160/90.
  • Be in good general health based on your health history, exam, blood and urine tests, and heart test.
  • Have no weight change greater than 1.5 kg (about 3 pounds) in the past 3 months, and not do very heavy exercise.
  • Use diet, metformin, sulfonylureas, or both medicines to treat diabetes. If taking a GLP-1 drug, the dose must be unchanged for at least 3 months; for a DPP-4 drug, at least 2 months.
  • Have stopped SGLT2 drugs at least 2 months before screening, as directed by the study team. Statins are allowed if the dose has been unchanged for at least 3 months.

Who can't join

  • Use insulin or thiazolidinediones (TZDs), a type of diabetes medicine.
  • Take other medicines that affect blood sugar, apart from the diabetes medicines allowed by the study.
  • Have taken an SGLT2 drug within 2 months before screening. Some people may qualify later if they agree to stop it under the study team's plan.
  • Have proliferative retinopathy, an eye disease with abnormal blood vessel growth, or an eGFR below 60.
  • Be a woman who could become pregnant and is not using suitable birth control.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Patients with T2D Inclusion Criteria: * 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 * Blood Pressure (BP)≤160/90 mmHg * Participants must be in general good health based on medical history, physical exam, screening blood chemistries, CBC (Complete Blood Count), TSH/T4 (thyroid/thyroxine hormone), EKG (electrocardiogram), and urinalysis (UA) * Stable body weight (±1.5 kg) over the last 3 months and must not participate in an excessively heavy exercise program * Patients treated with diet, Sulfonylureas, Metformin, or Sulfonylureas/Metformin (Sulfo/MET) * Participants receiving a Glucagon like peptide -1 receptor agonist (GLP1-RA) must be on a stable dose for at least three months prior to study enrollment. * Participants receiving a Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitor) must be on a stable dose for at least two months prior to study enrollment. * SGLT2 inhibitors must be discontinued at least two months prior to study enrollment. * Statin therapy is permissible if the dose has been stable for at least 3 months EXCLUSION CRITERIA An individual who meets any of the following criteria will be excluded from participation in this study: * 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. If their HbA1c rises to greater than 10%, treatment will be initiated with either metformin, a DPP-4 inhibitor, or a sulfonylurea. We do not anticipate any adverse effects during this initial period, provided the HbA1c remains below 10%. HbA1c will be measured using a fingerstick test, which requires only a minimal amount of blood. No compensation will be provided during this phase. After two months of medication discontinuation, participants will return for a screening visit. If they meet all eligibility criteria, they will be enrolled in the study and payment done by protocol.

Study sites (1)

TX