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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.