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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
256
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: 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.
Sitagliptin: will be administered as a 100mg dose once daily.
University Health System Texas Diabetic Institute
San Antonio, Texas, United States
RECRUITINGUT Health Science Center
San Antonio, Texas, United States
RECRUITINGnumber 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
Time frame: 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.
Time frame: month 60
Change in insulin sensitivity
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
Time frame: from baseline to end of study (60 months)
Change in Beta Cell Function
A calculated value using plasma glucose, insulin and C-peptide concentrations during the Oral Glucose Tolerance Test (OGTT) test.
Time frame: Baseline to end of study (60 months)
Change in body weight
Change from study beginning to end, measured in kilograms (kg)
Time frame: Baseline to end of study (60 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Metformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg.