The Efficacy of Sodium-glucose Co-transporter 2 Inhibitor or Dipeptidyl Peptidase-4 Inhibitor in Type 2 Diabetes Patients With Premix Insulin

Study Overview
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Brief Summary
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The population of type 2 diabetes increased enormously worldwide. As disease progression, uncontrolled type 2 diabetes patients need multiple daily insulin injections, but the risk of body weight gain and hypoglycemia will increase. In recent years, the newly oral anti-hypoglycemic agents developed, such as dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The former indirectly stimulate insulin secretion and suppress glucagon through increase incretin. The later inhibit re-absorption of blood glucose in proximal renal tubule to improve hyperglycemia. According to the guideline published in 2017 by American diabetes Associations, if patients received premix insulin injections twice daily and their glycemic control can't meet the target, increase the frequency of injection such as basal bolus would be considered. However, it is difficult for some patients and it may cause more hypoglycemia and gain of body weight. Because previous report revealed dipeptidyl peptidase-4 inhibitors or sodium-glucose co-transporter 2 inhibitors added to insulin resulted in better glycemic control, but there was no direct comparison, so we design this study to observe the efficacy of these two drugs in uncontrolled diabetes patient received twice daily insulin injections.

Official Title
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The Efficacy and Safety of Sodium-glucose Co-transporter 2 Inhibitor or Dipeptidyl Peptidase 4 Inhibitor Added to Premix Insulin Injection Twice Daily in Uncontrolled Type 2 Diabetes Patients

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Drug: SGLT2 inhibitor (Empagliflozin 25 MG)
* Drug: DPP4 inhibitor (Linagliptin 5 MG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes patient received premix insulin twice daily and HbA1c>7% >20 years old Exclusion Criteria: Type 1 diabetes and gestational diabetes Diabetic ketoacidosis in previous 6 months Urinary tract infection in previous 6 months Pancreatitis in previous 6 months estimated GFR<45 mL/min/1.73m2 Patient whom already received DPP4 inhibitor or SGLT2 inhibitor

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGLT2 inhibitor (Empagliflozin 25 MG)<br>We add SGLT2 inhibitor (Empagliflozin 25 MG, oral, once daily) to type 2 diabetes patient poorly controlled with premix insulin therapy for 6 months. | Drug: SGLT2 inhibitor (Empagliflozin 25 MG)<br>* We randomized add SGLT2 inhibitor (Empagliflozin 25 MG) or DPP4 inhibitor (Linagliptin 5 MG) to type 2 diabetes patient poorly controlled with premix insulin therapy.<br>* Other names: Jardiance;|
| Active Comparator: DPP4 inhibitor (Linagliptin 5 MG)<br>We add DPP4 inhibitor (Linagliptin 5 MG, oral, once daily) to type 2 diabetes patient poorly controlled with premix insulin therapy.for 6 months. | Drug: DPP4 inhibitor (Linagliptin 5 MG)<br>* We randomized add SGLT2 inhibitor (Empagliflozin 25 MG) or DPP4 inhibitor (Linagliptin 5 MG) to type 2 diabetes patient poorly controlled with premix insulin therapy.<br>* Other names: Trajenta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin (HbA1c) | change in glycated hemoglobin (HbA1c) in percentage from baseline to week 24 | measurement at baseline, 12 week and 24 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood glucose | change in fasting blood glucose in mg/dl from baseline to week 24 | measurement at baseline, 12 week and 24 week | 
| Postprandial blood glucose | change in postprandial blood glucose in mg/dl from baseline to week 24 | measurement at baseline, 12 week and 24 week | 
| Body weight | change in body weight in kilogram from baseline to week 24 | measurement at baseline, 12 week and 24 week | 
| Hypoglycemia event | documented hypoglycemia (glucose monitor <70mg/dl with hypoglycemia associated symptoms) from baseline to week 24 | recorded at 12 week and 24 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGLT2 inhibitor, DPP4 inhibitor