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

NCT06922656 | Not Yet Recruiting Phase 4

• 1 other identifier: RAHM2023013
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 3

Brief Summary

Previous data from our clinical trial has demonstrated that the combination of dapagliflozin plus pioglitazone cause robust decrease in the plasma glucose concentration without significant increase in plasma ketone concentration in subjects with T1DM receiving multiple insulin injections or insulin pump. Although patients receiving insulin therapy with pump have participated in the study, none has insulin delivered in automated pump (780 pump) which automatically adjusts the rate of insulin infusion based upon the measured plasma glucose concentration. Although automated insulin pumps have been introduced to practice only last year, they are gaining popularity in the care of T1DM patients worldwide. The aim of this amendment is to demonstrate the efficacy (decrease in HbA1c) and safety (no significant increase in plasma ketone concentration) of combination of dapagliflozin plus pioglitazone in T1DM patients receiving insulin therapy with automated insulin pump.

Conditions

Type 1 Diabetes

Keywords

Ketoacidosis; Hypoglycemia; Glucose Control; SGLT2 Inhibitors; Pioglitazone

Outcome Measures

Primary Outcomes (1)

• HbA1C Reduction

  1\) The primary objective of the study is to examine the decrease in HbA1c caused by pioglitazone plus dapagliflozin versus placebo in T1DM patients receiving automated insulin delivery (780 pump).

  16 weeks

Secondary Outcomes (1)

• Time in Range

  16 weeks

Study Arms (2)

Pioglitazone and Dapagliflozin

ACTIVE COMPARATOR

Group 1 will be started on dapagliflozin 10 mg per day plus 30 mg pioglitazone.

Drug: Dapagliflozin (DAPA); Drug: Pioglitazone 45 mg

Placebo

PLACEBO COMPARATOR

Group 2 will receive matching placebo

Drug: Placebo

Interventions

Dapagliflozin (DAPA) DRUG

The hypothesis tested in the original study was whether the addition of pioglitazone in patients with type 1 diabetes mellitus (T1DM) receiving therapy with dapagliflozin would amplify the decrease in HbA1c and prevent the increase in plasma ketone concentration caused by dapagliflozin.

Pioglitazone and Dapagliflozin

Pioglitazone 45 mg DRUG

The hypothesis tested in the original study was whether the addition of pioglitazone in patients with type 1 diabetes mellitus (T1DM) receiving therapy with dapagliflozin would amplify the decrease in HbA1c and prevent the increase in plasma ketone concentration caused by dapagliflozin.

Pioglitazone and Dapagliflozin

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• \- 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.
• \) 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

You may not qualify if:

• \) 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.
• \) 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

Sponsors & Collaborators

• Dasman Diabetes Institute: lead

Study Sites (3)

Dasman Diabetes Institute

Kuwait City, 1180, Kuwait

Location

Hamad Medical Corporation

Doha, Qatar

Location

Diabetes and Endocrine Treatment Center, Prince Sultan Military Medical City. Kidney & Pancreas Health Centre, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital & Research Centre, Alfaisal Univeristy, Riyadh, Kingdom of Saudi Arabia

Riyadh, Saudi Arabia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Ketosis; Hypoglycemia

Interventions

dapagliflozin; Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Acidosis; Acid-Base Imbalance

Intervention Hierarchy (Ancestors)

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

Study Officials

• Fahd Al-Mulla, MD, PhD

  Dasman Diabetes Institute

  STUDY CHAIR

• Muhammed Abdul Ghani, MD, PhD

  Texas Diabetes Institute, Dasman Diabetes Institute

  PRINCIPAL INVESTIGATOR

• Mohamed Abu-Farha, PhD

  Dasman Diabetes Institute

  STUDY DIRECTOR

Central Study Contacts

Mohamed Abu-farha, PhD

CONTACT

965-22242999; Mohamed.abufarha@dasmaninstitute.org

Study Design

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

Model Details: Eligible subjects without evidence of hypoglycemia will be randomized in a double blind fashin into two groups to receive for 16 weeks in a double-blind fashion the following: Group 1 will be started on dapagliflozin 10 mg per day plus 30 mg pioglitazone. If well tolerated, the pioglitazone dose will be increased to 45 mg after 2 weeks. Subjects in Group 2 will receive matching placebo. Subjects in both groups will be provided with ketone meters and will be asked to measure their plasma ketone concentration every morning. If the plasma ketone concentration exceeds 1.0 mM, subjects will be instructed to contact the study nurse coordinator.

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 10, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: August 29, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Access Criteria: Access will be allowed after communicating with PI and approval of steerng committee

Locations

KU (1); SA (1); QA (1)