Purpose

The goal of this randomized, open labelled clinical trial is to examine the efficacy, durability, and mechanism of HbA1c reduction produced by the combination of pioglitazone plus tirzepatide versus metformin plus sitagliptin in recently diagnosed type 2 diabetes mellitus patients.
The main question[s] it aims to answer are:
How effective is the combination of pioglitazone plus tirzepatide in managing blood sugar levels in people with type 2 diabetes?
How does this combination compare to the use of metformin plus sitagliptin in controlling blood sugar levels?

Category

IRB Number
STUDY00000139
NCT Number
NCT06246799
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

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

Principal Investigator
Muhammad Abdul-Ghani

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

Erwin Nepomuceno

nepomucenoe@uthscsa.edu



Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    1. Ability of subject to understand and the willingness to sign a written informed consent document. 2. Males and females; Age 18-75 years 3. Recently (within 5 years) diagnosed Type 2 Diabetes Mellitus (T2DM) patients 4. Drug naïve or receiving metformin monotherapy 5. HbA1c >6.5% (no limit on upper HbA1c value); 6. Willingness to adhere to the investigational product regimen 7. Good general health 8. Stable body weight over the preceding 3 months 9. Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria

    1. positive anti-GAD (antibodies to glutamic acid decarboxylase) 2. pregnancy or plan of becoming pregnant 3. evidence of proliferative diabetic retinopathy, 4. plasma creatinine >1.4 females or >1.5 males; 5. presence of congestive heart failure (CHF); 6. history of cancer (<5 years); 7. prior history of pancreatitis, 8. bladder cancer or family history of thyroid tumors; 9. presence of hematuria in the urine analysis.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
Primary Purpose
Other
Masking
None (Open Label)
Condition
  • Type 2 Diabetes (Adult Onset)

    • Arm Groups

    ArmDescriptionIntervention
    Active Comparator

    Group IA

    		Tirzepatide will be started at 2.5mg and increased to 15mg by month 4. At month 6, Pioglitazone will be added to the Tirzepatide, 15 mg daily.
  • Drug: Pioglitazone

    Pioglitazone: Participants will begin therapy at 15mg daily for the first 4 weeks then increase dose to 30mg at week 4 and to 45 mg at week 8, as tolerated.

    Other names:

    • Actos

  • Drug: Tirzepatide

    Tirzepatide:Participants will be initiated on 2.5mg weekly and increase their dose to 5mg at week 4, 10mg at week 8 and 15mg at week 12 as tolerated.

    Other names:

    • Mounjaro

    • Experimental

    Group IC

    		Tirzepatide starting at 2.5mg weekly titrated to 15mg weekly (2.5 month 1, 5mg month 2, 10mg month 3 and 15mg at month 4) with Pioglitazone beginning at 15mg daily and ending at 45mg daily (15mg month 1, 30mg month 2 and 45mg at month 3 onwards).
  • Drug: Pioglitazone

    Pioglitazone: Participants will begin therapy at 15mg daily for the first 4 weeks then increase dose to 30mg at week 4 and to 45 mg at week 8, as tolerated.

    Other names:

    • Actos

  • Drug: Tirzepatide

    Tirzepatide:Participants will be initiated on 2.5mg weekly and increase their dose to 5mg at week 4, 10mg at week 8 and 15mg at week 12 as tolerated.

    Other names:

    • Mounjaro

    • Active Comparator

    Group 1B

    		Pioglitazone will be started at 15mg and increased to 45 mg by month 3. At month 6, tirzepatide 2.5mg will be started and increased weekly as tolerated.
  • Drug: Pioglitazone

    Pioglitazone: Participants will begin therapy at 15mg daily for the first 4 weeks then increase dose to 30mg at week 4 and to 45 mg at week 8, as tolerated.

    Other names:

    • Actos

  • Drug: Tirzepatide

    Tirzepatide:Participants will be initiated on 2.5mg weekly and increase their dose to 5mg at week 4, 10mg at week 8 and 15mg at week 12 as tolerated.

    Other names:

    • Mounjaro

    • Active Comparator

    Group II

    		Metformin starting at 1000mg XR daily and Sitagliptin 100mg daily at week 4, Metformin will be increased to 200mg.
  • Drug: Metformin HCI XR

    Metformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg.

    Other names:

    • Extended Release Metformin

  • Drug: Sitagliptin

    Sitagliptin: will be administered as a 100mg dose once daily.

    Other names:

    • Januvia

    •