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.
• 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.