Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin

Study Overview
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Brief Summary
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The objectives of this study are 1) to compare the effect of ipragliflozin 50 mg on glucose-lowering effect with sitagliptin 100 mg in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin, 2) to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers, 3) to examine changes of body composition including fat and muscle mass with volume status.

Detailed Description
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The objectives of this study are to compare the effect of 50mg of ipragliflozin, a SGLT2 inhibitor, on glucose-lowering effect with 100mg of sitagliptin, a DPP4 inhibitor in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin. We are also going to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers. Changes of body composition including fat and muscle mass with volume status will be also examined.

Official Title
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Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Ipragliflozin
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes with HbA1c 7.5% - 9.0% at screening visit Male or female between 20 and 75 years of age Patients taking sulfonylurea (glimepiride 1 8mg or gliclazide 30 120 mg or equivalent dose) and metformin (≥ 1000 mg or maximum tolerated dose) for more than 3 months BMI ≥23 kg/m² Estimated GFR ≥ 60 ml/min/1.73m² Women of child bearing potential must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose and must have a negative urinary pregnancy test. Exclusion Criteria: Type 1 diabetes, gestational diabetes, or diabetes with secondary cause Patients with acute coronary syndrome within 3 months prior to screening visit Patients with acute coronary syndrome within 3 months prior to screening visit Pregnant or breastfeeding women or reproductive-age women who refuse contraception Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT > 3-fold the upper limit of normal) Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ Other clinical trials within 30 days Alcohol abuse Contraindication to SGLT2 inhibitors or Dipeptidyl-peptidase 4 inhibitors Taking insulin, oral hypoglycemic agents other than metformin, sulfonylurea, and the study drugs.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Ipragliflozin<br>Ipragliflozin 50 mg in addition to their preexisting sulfonylurea and metformin ** Metformin and sulfonylurea's dosages Metformin 500 mg - 2550 mg Sulfonylurea: Glimepiride 1 mg - 8 mg or Gliclazide MR 30 mg - 120 mg | Drug: Ipragliflozin<br>* Ipragliflozin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes<br>* Other names: Suglat;|
| Active Comparator: Sitagliptin<br>Sitagliptin 100 mg in addition to their preexisting sulfonylurea and metformin ** Metformin and sulfonylurea's dosages Metformin 500 mg - 2550 mg Sulfonylurea: Glimepiride 1 mg - 8 mg or Gliclazide MR 30 mg - 120 mg | Drug: Sitagliptin<br>* Sitagliptin as add-on to Metformin and Sulfonylurea in patients with poorly controlled type 2 diabetes<br>* Other names: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin | Change of HbA1c after 24 weeks' treatment | Baseline, week 12, week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic target goal achievement | Glycemic target goal achievement (HbA1c < 7%) at week 24 | Baseline, week 12, week 24 | 
| Body weight | Change of body weight at week 24 | Baseline, week 12, week 24 | 
| Body fat mass | Change of body fat mass at week 24 | Baseline, week 24 | 
| Fasting plasma glucose level | Change of fasting plasma glucose level at week 24 | Baseline, week 12, week 24 | 
| Postprandial 2hr glucose level | Changes of postprandial 2hr glucose level at week 24 | Baseline, week 12, week 24 | 
| Blood Pressure | Change of systolic/diastolic blood pressure at week 24 | Baseline, week 12, week 24 | 
| Triglyceride/HDL-cholesterol ratio | Changes of triglyceride/HDL-cholesterol ratio at week 24 | Baseline, week 12, week 24 | 
| Uric acid | Changes of uric acid at week 24 | Baseline, week 12, week 24 | 
| Parathyroid hormone | Changes of parathyroid hormone at week 24 | Baseline, week 12, week 24 | 
| 25-hydroxyvitamin D | Changes of 25-hydroxyvitamin D at week 24 | Baseline, week 12, week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ipragliflozin, Sitagliptin