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

The University of Texas System (UT)

Status and phase: Enrolling; Phase 3

Conditions: Type 2 Diabetes (Adult Onset)

Treatments: Drug: Pioglitazone; Drug: Metformin HCI XR; Drug: Sitagliptin; Drug: Tirzepatide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06246799

R01DK097554 (U.S. NIH Grant/Contract)

STUDY00000139

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 256 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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256 participants in 4 patient groups

Group IC

Experimental group

Description:

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).

Treatment:

Drug: Tirzepatide

Drug: Pioglitazone

Group II

Active Comparator group

Description:

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

Treatment:

Drug: Sitagliptin

Drug: Metformin HCI XR

Group IA

Active Comparator group

Description:

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.

Treatment:

Drug: Tirzepatide

Drug: Pioglitazone

Group 1B

Active Comparator group

Description:

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.

Treatment:

Drug: Tirzepatide

Drug: Pioglitazone