Tests whether pioglitazone can block dapagliflozin's effect on ketones in type 1 diabetes

Trial details

Who runs it

The University of Texas Health Science Center at San Antonio

Trial code

NCT07056699

Record updated

20 July 2026

Original description

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.Read full original descriptionShow less

Protocol V: San Antonio Site Sub Study: Can Pioglitazone Block SGLT2 Inhibitor-induced Stimulation of Lipolysis, Ketone Production and Liver Glucose Production in Type I Diabetic Patients

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.

Inclusion: 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; Minor deviations may be permitted if:; The abnormality is not considered clinically significant; The deviation does not pose a safety risk or interfere with study participation; The rationale for inclusion is documented in the source records; Fasting C-peptide concentration <0.7 ng/ml; Poor glycemic control (HbA1c=7.0-11.0%); Treatment with multiple daily insulin injections (basal plus prandial) or insulin pump; Total daily insulin dose ≥0.6 U/kg per day; Stable insulin dose (±4 units) in the preceding three months; eGFR ≥ 50 ml/min; Weight stable over the preceding 3 months (± 4 pounds); Positive GAD antibody (Glutamic Acid Decarboxylase antibody). *; Testing for GAD antibodies will be performed during the screening visit. Participants who test positive for GAD antibodies will be eligible for enrollment in the study. Over time, these antibodies may disappear, reducing the likelihood of a positive result during screening. If participant tests negative for GAD antibodies, their medical history will be reviewed to determine whether testing for GAD antibodies was performed at an earlier stage of Type 1 Diabetes (T1D). If prior positive results are confirmed, the participant may be enrolled. If a participant tests positive for antibodies other than GAD, an exception request will be submitted to the Institutional Review Board (IRB) for approval.

Exclusion: Pregnancy, lactating, positive pregnancy test or planning to become pregnant in the following year. Women of child-bearing potential will be required to undergo a pregnancy test prior to enrollment and must agree to use effective contraception (at least two barrier methods) for the duration of the study; Participants with a history of radiation exposure exceeding 5 REM within the previous 12 months will be excluded; Prior to the screening period, potential participants will be pre-screened either by phone or in person at the Texas Diabetes Institute. Individuals with prior significant radiation exposure will be excluded; Type 2 Diabetes (T2D); History of hospitalization for DKA, hypoglycemia or uncontrolled hyperglycemia in the preceding 6 month; History of hypersensitivity to dapagliflozin or pioglitazone; HbA1c <7.0% or >11.0%; eGFR < 50 ml/min; Major organ system disease which includes: (i) malignancy or history of malignancy including bladder cancer; (ii) Congestive heart failure or history of coronary heart disease or any other cardiac disease; (iii) chronic liver disease or LFT >3 times the upper normal level; (iv) History of alcohol or drug abuse; (v) History of chronic lung disease (e.g., COPD, asthma); (vi) history of rheumatic disease; (vii) History of chronic pancreatitis or pancreatic surgery; (viii) History of CVA or TIA (ix) Planned surgery during the study; (x) history of HIV infection or other immune compromised disease; and history of organ transplantation; (xi) patients who take medications, other than insulin, known to affect glucose metabolism, e.g., prednisone; Daily insulin dose <0.6 U/kg per day; Fasting C-peptide >0.7 ng/ml; Hematuria in urine analysis; Evidence of proliferative diabetic retinopathy; Patients enrolled in a heavy exercise program; Patients on ketogenic diet; Presence of symptoms of poor glycemic control, e.g. polydipsia or polyurea.

ClinicalTrials.gov NCT07056699