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SGLT2i, Pioglitazone, and Ketone Production in T1D

ConditionType1diabetes
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe University of Texas Health Science Center at San Antonio

About this trial

Participants are being asked to be in a research study. Scientists do research to answer important questions which might help change or improve treatment of participants disease in the future.

In patients with Type 1 Diabetes (T1D), dapagliflozin a Selective Glucose Transporter 2 Inhibitor (SGLT2i) is known to increase production of glucose in the liver, increase breakdown of fats (lipolysis), and increase production of ketones (ketogenesis). Ketones are chemicals produced by the liver when the body breaks down fat for energy instead of glucose. When the level of ketones in the body becomes too high, a condition called ketoacidosis develops. In this study, the study team will investigate whether adding pioglitazone (a medication commonly used to treat type 2 diabetes), can reduce the dapagliflozin - induced liver glucose production, fat break down (lipolysis) and ketone body production (ketogenesis) in patients with T1D.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >18 years

T1D

Other than diabetes, subjects must be in good general health as determined by the investigator based on physical exam, medical history and screening labs.

The abnormality is not considered clinically significant.

Disqualifiers

Type 2 Diabetes (T2D)

Daily insulin dose <0.6 U/kg per day

Fasting C-peptide >0.7 ng/ml

HbA1c <7.0% or >11.0%

Trial design

Design model

Parallel

Treatments tested in this trial

  • Dapagliflozin 10mg Tab

    Drug

    Dapagliflozin (10 mg/day)

  • Pioglitazone 15 MG and 30mg

    Drug

    Pioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks)

  • Placebo

    Other intervention

    Inert placebo for Pioglitazone

Treatment groups

24 Participants
are divided into 2 treatment groups
Group A: Experimental study drug for T1DExperimental treatment 2 interventions
Group B: Placebo Group for T1DPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Change in endogenous glucose production (EGP)

Infusions of a tracer, ³H-glucose, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected minutes to assess how your body responds to the infused tracers. This tracer help to measure the rate of endogenous (liver) glucose production. The difference in levels of EGP will be reported from the beginning of the study to a second level taken 16 weeks later.

Time frame
Baseline (Week 0) to Week 16
2

Change in ketone body production ( ketogenesis)

Infusions of tracers, ³H-glucose and U-2H-glycerol or 14C-Glycerol, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers. This tracer help to measure the rate of ketone body production (ketogenesis). The difference in levels of ketones will be reported from the beginning of the study to a second level taken 16 weeks later.

Time frame
Baseline (Week 0) to Week 16
3

Change in lipolysis (fat breakdown)

Infusions of tracers, U-H-14C-Glycerol or 2H-Glycerol, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers. This tracer help to measure the rate of lipolysis (fat breakdown). The difference in levels of lipolysis will be reported from the beginning of the study to a second level taken 16 weeks later.

Time frame
Baseline (Week 0) to Week 16

Secondary outcomes

1

Change in HbA1c from baseline (Week 0) to Week 16

HbA1c and CGM metrics provide clinically relevant data on glycemic control and variability. This endpoint assess the metabolic efficacy of adding pioglitazone to dapagliflozin in T1DM.

Time frame
Baseline (Week 0) to Week 16
2

Change in plasma Free Fatty Acid (FFA) from baseline (Week 0) to Week 16.

Measuring free fatty acids directly tests the hypothesis that pioglitazone reduces the risk of SGLT2 inhibitor-associated diabetic ketoacidosis (DKA) by suppressing FFA release.

Time frame
Baseline (Week 0) to Week 16
3

Change in glycerol from baseline (Week 0) to week 16.

To examine the effects of adding pioglitazone (15/30 mg/day) to dapagliflozin (10 mg/day) compared to dapagliflozin (10mg/day) plus placebo in T1DM patients, focusing on lipolysis changes over a 16-week treatment period.

Time frame
Baseline (Week 0) to Week 16

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

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
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