Dapagliflozin Plus Pioglitazone in T1DM

NCT03878459 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: HSC20180515H
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

T1DM,ketoacidosis, dapagliflozin, pioglitazone

Outcome Measures

Primary Outcomes (1)

• Decrease in HbA1c

  28 weeks

Secondary Outcomes (2)

• plasma ketones

  28 weeks

• insulin dose

  28 weeks

Study Arms (2)

Intervention

EXPERIMENTAL

pioglitazone treatment

Drug: Pioglitazone 45 mg

control

PLACEBO COMPARATOR

subjects will receive placebo

Drug: Placebo

Interventions

Pioglitazone 45 mg DRUG

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

Intervention

Placebo DRUG

PATIENTS WILL RECEIVE PLACEBO

control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (3)

University Health System Texas Diabetic Institute

San Antonio, Texas, 78207, United States

ACTIVE NOT RECRUITING

Endocrinology and Diabetes Center, Rambam Medical Center

Haifa, Israel

ACTIVE NOT RECRUITING

Dasman Diabetes Institute

Kuwait City, Kuwait

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Muhammad Abdul-Ghani, MD, PhD

CONTACT

210 567 2391; ABDULGHANI@UTHSCSA.EDU

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo controlled intervention

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 18, 2019
• Study Start: August 8, 2019
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); IL (1); KU (1)