Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. We hypothesized that SGLT2 inhibitor will improve the ketone metabolism compared to dipeptidyl Peptidase-4 (DPP4) inhibitor. And we will also evaluate the association between ketone metabolism and cardiac remodeling evaluated by echocardiography. We will randomly assign 122 people with T2DM to receive dapagliflozin 10mg or gemigliptin 50mg. The primary endpoint are changes in acetoacetate, total ketone, beta-hydroxybutyric acid, left ventricular (LV) mass index, and LV global longitudinal strain during 6 months follow-up. This study may provide robust evidence of the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors.

Official Title
-----------------
Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes

Conditions
-----------------
Type2 Diabetes, Remodeling, Ventricular

Intervention / Treatment
-----------------
* Drug: Dapagliflozin
* Drug: Gemigliptin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects diagnosed with T2D on stable antidiabetic medication No recent use of SGLT2 inhibitor within 3 months Exclusion Criteria: HbA1c > 10% Pregnancy or breast feeding estimated GFR <45 30 mL/min/1.73㎡ insulin user

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin group<br>Dapagliflozin 10mg for 6 months. | Drug: Dapagliflozin<br>* The patients assigned to the Dapagliflozin group will take Farxiga Pill 10mg for 6 months.<br>|
| Placebo Comparator: Gemigliptin group<br>Gemigliptin 50mg for 6 months. | Drug: Gemigliptin<br>* The patients assigned to the Gemigliptin group will take Zemiglo Pill 50mg for 6 months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (%) in acetoacetate, total ketone, beta-hydroxybutyric acid | The change of acetoacetate, total ketone, beta-hydroxybutyric acid from baseline to 6 months follow-up | 6 months | 
| Change (%) in LV mass index | The change of LV mass index from baseline to 6 months follow-up | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (%) in LV ejection global longitudinal strain | The change of LV mass ejection global longitudinal strain from baseline to 6 months follow-up | 6 months | 
| Change (%) in mean 24hr ambulatory systolic and diastolic blood pressure | The change of mean 24hr ambulatory systolic and diastolic blood pressurefrom baseline to 6 months follow-up | 6 months |