Combining dapagliflozin and pioglitazone for better glucose control in type 1 diabetes

Can Addition of Pioglitazone to SGLT2 Inhibitor in Type 1 Diabetic Patients Amplify the Decrease in HbA1c and Prevent the Increase in Plasma Ketone Concentration?

This study is testing if adding two medications, dapagliflozin and pioglitazone, to insulin therapy can help people with type 1 diabetes better control their blood sugar without causing serious side effects.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (other)
• Drugs / interventions: prednisone
• Locations: 3 sites (San Antonio, Texas and 2 other locations)
• Trial ID: NCT03878459 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of adding dapagliflozin, an SGLT2 inhibitor, and pioglitazone, a thiazolidinedione, to insulin therapy in patients with type 1 diabetes mellitus (T1DM). A total of 120 eligible participants will undergo a 4-week run-in period followed by 12 weeks of dapagliflozin treatment, after which they will be randomized to receive either pioglitazone or a placebo for 16 weeks. The study will utilize mixed meal tolerance tests, indirect calorimetry, and continuous glucose monitoring to assess the impact on glucose control and plasma ketone levels. The goal is to determine if this combination can reduce HbA1c without increasing the risk of ketoacidosis or hypoglycemia.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with type 1 diabetes, poor glycemic control, and stable insulin doses.

Not a fit: Patients with type 2 diabetes or those with well-controlled HbA1c levels may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved glucose control and reduced insulin requirements for patients with type 1 diabetes.

How similar studies have performed: While SGLT2 inhibitors have shown promise in type 1 diabetes, the combination with pioglitazone is a novel approach that has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Age \>18 years
* T1DM
* Good general health
* Fasting C-peptide concentration \<0.7 ng/ml
* Poor glycemic control (HbA1c=7.0-11.0%)
* Treatment with multiple daily insulin injections or insulin pump
* Total daily insulin dose ≥0.6 U/kg per day
* Stable insulin dose (±4 units) in the preceding three months.
* eGFR≥60 ml/min
* Weight stable over the preceding 3 months (± 3 pounds)
* Do not participate in an excessively heavy exercise program

Exclusion Criteria:

* T2DM
* Daily insulin dose \<0.6 U/kg per day
* Fasting C-peptide \>0.7 ng/ml
* HbA1c \<7.0% or \>11.0%
* eGFR\<60 ml/min
* Hematuria in urine analysis
* 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.
* 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.
* Evidence of proliferative diabetic retinopathy
* Patients enrolled in a heavy exercise program
* Patients on ketogenic diet
* History of hospitalization for DKA, hypoglycemia or uncontrolled hyperglycemia in the preceding 6 month.
* Presence of symptoms of poor glycemic control, e.g. polydipsia or polyurea
* History of hypersensitivity to dapagliflozin or pioglitazone

Where this trial is running

San Antonio, Texas and 2 other locations

• University Health System Texas Diabetic Institute — San Antonio, Texas, United States (ACTIVE_NOT_RECRUITING)
• Endocrinology and Diabetes Center, Rambam Medical Center — Haifa, Israel (ACTIVE_NOT_RECRUITING)
• Dasman Diabetes Institute — Kuwait City, Kuwait (RECRUITING)

Study contacts

• Study coordinator: Muhammad Abdul-Ghani, MD, PhD

Conditions: Type 1 Diabetes Mellitus, T1DM,ketoacidosis, dapagliflozin, pioglitazone