Comparative Effectiveness of Two Initial Combination Therapies in Patients With Recent Onset Diabetes

NCT ID: NCT06246799

Last Updated: 2025-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

256 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-07

Study Completion Date

2029-06-30

Brief Summary

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The primary purpose of this study is to evaluate the efficacy, durability, and mechanism of HbA1c reduction produced by the combination of pioglitazone plus tirzepatide compared to metformin plus sitagliptin in patients with recently diagnosed type 2 diabetes mellitus.

Detailed Description

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This is a randomized open label controlled 2 arm study (with one of the arms containing 3 sub-groups) which aims to examine the effectiveness and long term effects on HbA1c reduction produced by the combination of pioglitazone plus tirzepatide versus metformin plus sitagliptin in recently diagnosed type 2 diabetes mellitus (T2DM) patients.

A subgroup of patients from group 1 will be invited to participate in a sub-study which lasts for 6 months and aims at exploring the metabolic/molecular mechanisms responsible for the study results. The selection of subjects to each subgroup will be done randomly and the end of sub-study, subjects will continue therapy and follow-up from month 6 on in the main study.

Conditions

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Type 2 Diabetes (Adult Onset)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

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.

Pioglitazone

Intervention Type DRUG

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.

Group II

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

Group Type ACTIVE_COMPARATOR

Sitagliptin

Intervention Type DRUG

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

Metformin HCI XR

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Tirzepatide

Intervention Type DRUG

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.

Pioglitazone

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Tirzepatide

Intervention Type DRUG

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.

Pioglitazone

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Sitagliptin

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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Mounjaro Actos Januvia Extended Release Metformin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Muhammad Abdul-Ghani, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

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University Health System Texas Diabetic Institute

San Antonio, Texas, United States

Site Status RECRUITING

UT Health Science Center

San Antonio, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Muhammad Abdul-Ghani, MD

Role: CONTACT

210-567-6691

Gozde Baskoy, PhD

Role: CONTACT

210-358-7200

Facility Contacts

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Muhammad Abdul-Ghani, MD

Role: primary

210-567-2391

Other Identifiers

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R01DK097554

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00000139

Identifier Type: -

Identifier Source: org_study_id

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