SGLT2i, Pioglitazone, and Ketone Production in T1D

Launched by THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO · Jul 7, 2025

Keywords

ClinConnect Summary

This clinical trial is studying how adding a medicine called pioglitazone might affect the changes caused by another medicine, dapagliflozin, in people with Type 1 Diabetes (T1D). Dapagliflozin can increase the amount of sugar made by the liver and cause the body to break down more fat, which leads to higher levels of ketones—chemicals the body makes when it uses fat for energy instead of sugar. Too many ketones can cause a serious condition called ketoacidosis. This study wants to see if pioglitazone can reduce these effects and help improve treatment for people with T1D.

People eligible for this study are adults over 18 with Type 1 Diabetes who have less than ideal blood sugar control (an HbA1c between 7% and 11%) and are already using multiple daily insulin injections or an insulin pump. Participants should be generally healthy aside from diabetes and have stable insulin doses and kidney function. Pregnant women, people with certain health problems, or those recently hospitalized for diabetes complications are not eligible. Those who join the study will be closely monitored by the research team to understand how these medicines work together and to ensure their safety throughout the trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age \>18 years
• • 2. T1DM
• • 3. Other than diabetes, subjects must be in good general health as determined by physical exam, medical history, Chem 20, CBC, TSH, urinalysis, and EKG.
• • 4. Fasting C-peptide concentration \<0.7 ng/ml
• • 5. Poor glycemic control (HbA1c=7.0-11.0%)
• • 6. Treatment with multiple daily insulin injections (basal plus prandial) or insulin pump
• • 7. Total daily insulin dose ≥0.6 U/kg per day
• • 8. Stable insulin dose (±4 units) in the preceding three months.
• • 9. eGFR≥60 ml/min
• • 10. Weight stable over the preceding 3 months (± 3 pounds) and who do not participate in an excessively heavy exercise program
• Exclusion Criteria:
• • 1. T2DM
• • 2. Daily insulin dose \<0.6 U/kg per day
• • 3. Fasting C-peptide \>0.7 ng/ml
• • 4. HbA1c \<7.0% or \>11.0%
• • 5. eGFR\<60 ml/min
• • 6. Hematuria in urine analysis
• • 7. Pregnancy, lactating, positive pregnancy test or planning to become pregnant in the following year. Women of child-bearing potential will be requested to use at least two barrier methods before being enrolled in the study.
• • 8. 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.
• • 9. Evidence of proliferative diabetic retinopathy
• • 10. Patients enrolled in a heavy exercise program
• • 11. Patients on ketogenic diet
• • 12. History of hospitalization for DKA, hypoglycemia or uncontrolled hyperglycemia in the preceding 6 month.
• • 13. Presence of symptoms of poor glycemic control, e.g. polydipsia or polyurea
• • 14. History of hypersensitivity to dapagliflozin or pioglitazone