Purpose

Purpose: To examine the effect of addition of combination therapy with dapagliflozin plus pioglitazone to insulin on glucose control and plasma ketone concentration in patients with type 1 diabetes (T1DM) Research Design: 120 patients with type 1 diabetes who otherwise are healthy constitute the study population. After screening, eligible subjects will start 4 week run in. At week 4, subjects will receive dapagliflozin for 12 weeks. At week 16, subjects will be randomized to receive in a double blind fashion pioglitazone or placebo for 16 weeks.

Methods: the following techniques will be employed in the present study: (1) mixed meal tolerance test; (2) indirect calorimetry; (3) continuous glucose monitoring.

Clinical Relevance: the results of the present study will demonstrate that the addition of pioglitazone to SGLT2 inhibitor in T1DM patients produces greater reduction in the HbA1c without increasing risk of ketoacidosis and hypoglycemia.

Category

IRB Number
20180515HU
NCT Number
NCT03878459
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

Principal Investigator
Muhammad Abdul-Ghani

Andrea Hansis-Diarte
210-567-3208
hansisdiarte@uthscsa.edu



Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
placebo controlled intervention
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Condition
  • Type 1 Diabetes Mellitus

    • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Intervention

    		pioglitazone treatment
  • Drug: Pioglitazone 45 mg

    patients will be started on 15 mg and the dose escalated to the maximal tolerated dose

    • Placebo Comparator

    control

    		subjects will receive placebo
  • Drug: Placebo

    PATIENTS WILL RECEIVE PLACEBO

    •