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

NCT06246799 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: STUDY00000139R01DK097554
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Type 2 Diabetes (Adult Onset)

Outcome Measures

Primary Outcomes (2)

• number of subjects achieving HbA1c <6.5% at 6 months (Efficacy)

  Therapy failure will be determined as HbA1c \>6.5% in two consecutive HbA1c measurements 3 months apart. Time to cumulative incidence of therapy failure curves will be created in subjects receiving pioglitazone/tirzepatide versus subjects receiving metformin/sitagliptin

  6 months

• Number of subjects failing to achieving HbA1c <6.5% Long-term

  The failure to achieving HbA1c \<6.5% (Durability) at the end of study in subjects receiving pioglitazone/tirzepatide (Group I) versus metformin/sitagliptin (Group II) in two consecutive HbA1c measurements 3 months apart.

  month 60

Secondary Outcomes (3)

• Change in insulin sensitivity

  from baseline to end of study (60 months)

• Change in Beta Cell Function

  Baseline to end of study (60 months)

• Change in body weight

  Baseline to end of study (60 months)

Study Arms (4)

Group IC

EXPERIMENTAL

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: Tirzepatide; Drug: Pioglitazone

Group II

ACTIVE COMPARATOR

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

Drug: Sitagliptin; Drug: Metformin HCI XR

Group IA

ACTIVE COMPARATOR

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: Tirzepatide; Drug: Pioglitazone

Group 1B

ACTIVE COMPARATOR

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: Tirzepatide; Drug: Pioglitazone

Interventions

Tirzepatide 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.

Also known as: Mounjaro

Group 1B; Group IA; Group IC

Pioglitazone 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.

Also known as: Actos

Group 1B; Group IA; Group IC

Sitagliptin DRUG

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

Also known as: Januvia

Group II

Metformin HCI XR DRUG

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

Also known as: Extended Release Metformin

Group II

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The University of Texas Health Science Center at San Antonio: lead

Study Sites (2)

University Health System Texas Diabetic Institute

San Antonio, Texas, 78207, United States

RECRUITING

UT Health Science Center

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tirzepatide; Pioglitazone; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Pyrazines

Study Officials

• Muhammad Abdul-Ghani, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Muhammad Abdul-Ghani, MD

CONTACT

210-567-6691; abdulghani@uthscsa.edu

Gozde Baskoy, PhD

CONTACT

210-358-7200; baskoy@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 7, 2024
• Study Start: November 7, 2024
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At study completion at the time of publication.

Locations

US (2)