Type 2 DiabetesPhase 1NCT05960656
SGLTi, Hepatic Glucose Production and Ketogenesis
A Phase 1 study testing Empagliflozin 25 MG in people with Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Empagliflozin 25 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2023to 30 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Texas Diabetes Institute/UH
San Antonio, Texas, 78229-3900
Ralph DeFronzo, MD, 210-358-7200, defronzo@uthscsa.edu
Aurora Merovci, MD, 210-567-6691, merovci@uthscsa.edu
About this study
Official title: Protocol l: SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis
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.
Read the detailed description
MAIN STUDY
Participants: 30 T2D subjects, age = 30-75 y, BMI = 23-38 kg/m2, HbA1c = 7.0-11%, eGFR > 60 ml/min/1.73m2, BP < 160/90 mmHg. Participants must be in general good health based on medical history, physical exam, screening blood chemistries, CBC, TSH/T4, EKG, and urinalysis. Patients must have 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, SU, metformin, or SU/MET are eligible. Patients treated with GLP-1 RA, DPP-4i, TZD, or insulin are excluded. Patients taking medications (other than SU/MET) known to affect glucose metabolism are excluded. Statin therapy is permissible if the dose has been stable for at least 3 months. Subjects with evidence of proliferative retinopathy or eGFR < 60 are excluded. Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices.
Protocol: Subjects will be randomized to receive empagliflozin (n=20) or placebo (n=10) in 2:1 ratio. Subject stratification will be done according to the following parameters: age (> or < 50 y), BMI (> or < 30 kg/m2), eGFR (> or < 80 ml/min/1.73 m2), HbA1c (> or < 8.5%). Each subject will participate in two studies performed in random order with 7-10 day interval between studies. 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. Study 1b will be similar to Study 1a with one exception. EGP, lipolysis, and ketogenesis, and NE turnover will be measured under pancreatic clamp conditions.
- Conditions
- Type 2 Diabetes
- Being tested
- Empagliflozin 25 MG, Placebo
- Keywords
- Pancreatic clamp, Endogenous glucose production, Ketogenesis, Gluconeogenesis, Lipolysis, Norepinephrine turnover
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MGDrug
Also called Jardiance
A medication used in the management and treatment of type 2 diabetes mellitus. It is in the sodium-glucose co-transporter (SGLT-2) class of medications.
PlaceboOther
Also called Placebo for empagliflozin
Inert tablet
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Experimental | Empagliflozin 25 mg/day Receives: Drug: Empagliflozin 25 MG |
| Placebo/Control Group | Placebo comparator | Placebo control Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endogenous Glucose Production (EGP)
Measurement of Endogenous Glucose Production (EGP) using stable isotope (6,6, D2- glucose infusion).
Measured: 0 and 300 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2023
- Study start5 Oct 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized controlled 2 arm clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ralph DeFronzo, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05960656
- Sponsor's protocol ID
- HSC20230457H - 440509
- Other IDs
- R01DK024092
- Status last verified
- Jul 2026
- First submitted
- 13 Jul 2023
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified data will be shared with NIH and as a publication in a peer reviewed journal once data are published.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol l: SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis
- ClinicalTrials.gov ID
- NCT05960656
- Acronym / sponsor ID
- HSC20230457H - 440509
- Conditions
- Type 2 Diabetes
- Keywords
- Pancreatic clamp, Endogenous glucose production, Ketogenesis, Gluconeogenesis, Lipolysis, Norepinephrine turnover
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 5 Oct 2023 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 27 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
MAIN STUDY
Participants: 30 T2D subjects, age = 30-75 y, BMI = 23-38 kg/m2, HbA1c = 7.0-11%, eGFR > 60 ml/min/1.73m2, BP < 160/90 mmHg. Participants must be in general good health based on medical history, physical exam, screening blood chemistries, CBC, TSH/T4, EKG, and urinalysis. Patients must have 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, SU, metformin, or SU/MET are eligible. Patients treated with GLP-1 RA, DPP-4i, TZD, or insulin are excluded. Patients taking medications (other than SU/MET) known to affect glucose metabolism are excluded. Statin therapy is permissible if the dose has been stable for at least 3 months. Subjects with evidence of proliferative retinopathy or eGFR < 60 are excluded. Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices.
Protocol: Subjects will be randomized to receive empagliflozin (n=20) or placebo (n=10) in 2:1 ratio. Subject stratification will be done according to the following parameters: age (> or < 50 y), BMI (> or < 30 kg/m2), eGFR (> or < 80 ml/min/1.73 m2), HbA1c (> or < 8.5%). Each subject will participate in two studies performed in random order with 7-10 day interval between studies. 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. Study 1b will be similar to Study 1a with one exception. EGP, lipolysis, and ketogenesis, and NE turnover will be measured under pancreatic clamp conditions.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- A randomized controlled 2 arm clinical trial
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Experimental | Drug: Empagliflozin 25 MGEmpagliflozin 25 mg/day |
| Placebo/Control Group | Placebo comparator | Other: PlaceboPlacebo control |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 MGAlso: JardianceA medication used in the management and treatment of type 2 diabetes mellitus. It is in the sodium-glucose co-transporter (SGLT-2) class of medications. | Drug | Empagliflozin |
| PlaceboAlso: Placebo for empagliflozinInert tablet | Other | Placebo/Control Group |
Primary outcome
Endogenous Glucose Production (EGP)
Time frame: 0 and 300 minutes
Measurement of Endogenous Glucose Production (EGP) using stable isotope (6,6, D2- glucose infusion).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Individual participant dataSharing planned: Yes. Deidentified data will be shared with NIH and as a publication in a peer reviewed journal once data are published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ralph DeFronzo, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Empagliflozin 25 MG in people with Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ralph DeFronzo, MD (210-567-6691, defronzo@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endogenous Glucose Production (EGP) (time frame: 0 and 300 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.