Type 2 Diabetes (Adult Onset)
Conditions
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.
Detailed 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.
Interventions
DRUGTirzepatide
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.
DRUGPioglitazone
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.
DRUGSitagliptin
Sitagliptin: will be administered as a 100mg dose once daily.
DRUGMetformin HCI XR
Metformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg.
Sponsors
The University of Texas Health Science Center at San Antonio
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number of subjects achieving HbA1c <6.5% at 6 months (Efficacy) | 6 months | 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 |
| Number of subjects failing to achieving HbA1c <6.5% Long-term | month 60 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin sensitivity | from baseline to end of study (60 months) | Matsuda Index of insulin sensitivity or total glucose disposal measured with the clamp.These are the gold standard methods for quantification insulin sensitivity with the OGTT or a euglycemic clamp |
| Change in Beta Cell Function | Baseline to end of study (60 months) | A calculated value using plasma glucose, insulin and C-peptide concentrations during the Oral Glucose Tolerance Test (OGTT) test. |
| Change in body weight | Baseline to end of study (60 months) | Change from study beginning to end, measured in kilograms (kg) |
Countries
United States
Contacts
CONTACTMuhammad Abdul-Ghani, MD
CONTACTGozde Baskoy, PhD
PRINCIPAL_INVESTIGATORMuhammad Abdul-Ghani, MD
The University of Texas Health Science Center at San Antonio
Outcome results
None listed