Triple Combination Therapy in Type 2 Diabetic Patients Who Had Inadequate Glycemic Control With Combination Therapy

Study Overview
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Brief Summary
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To assess the efficacy of treatment with sitagliptin or dapagliflozin or lobeglitazone in type 2 diabetes mellitus patients, who had inadequate glycemic control even though use of two drug combination therapy with glimepiride and metformin.

Detailed Description
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Dual combination therapy with metformin and sulphonylurea is the most commonly used combination regimen to treat patients with type 2 diabetes. But, treatment with the dual combination therapy is often unsuccessful at achieving glycaemic control in patients with type 2 diabetes. Recently, various oral hypoglycemic agents were developed including dipeptidyl peptidase (DPP)-IV inhibitor, sodium-glucose cotransporter 2 (SGLT2) inhibitor and new peroxisome proliferator-activated receptors (PPARs) agonists. But, there have been few studies about the glucose lowering effect of these drugs in Type 2 diabetes patients on the dual combination therapy with a sulfonylurea agent and metformin. Hence, the researchers plan to investigate the efficacy and safety of these drugs in combination with a sulfonylurea agent and metformin in type 2 diabetic patients.

Official Title
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Therapeutic Efficacy and Safety of Sitagliptin, Dapagliflozin and Lobeglitazone in Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Glimepiride and Metformin.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Dapagliflozin
* Drug: Lobeglitazone
* Drug: Glimepirde
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 ≤ Age < 80 years HbA1c ≥ 7 % combination therapy with glimepiride and metformin over 2 months. dosage of glimepiride : 1-8mg/day dosage of metformin : 500-2550mg/day Exclusion Criteria: Type 1 diabetes, gestational diabetes, or secondary forms of diabetes Contraindication to sitagliptin or dapagliflozin or lobeglitazone Pregnant or breast feeding women Medication which affect glycemic control (ex. steroid) Disease which affect efficacy and safety of drugs Any major illness (Liver disease, Renal failure, Heart disease, Cancer, etc) Not appropriate for oral antidiabetic agent

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glimepirde, Metformin, Sitagliptin<br>Dipeptidyl peptidase-4 (DPP4) inhibitor Sitagliptin | Drug: Sitagliptin<br>* 100mg qd per oral during 24months compared with other treatment groups<br>* Other names: Januvia;Drug: Glimepirde<br> <br> * Other names: Amaryl;Drug: Metformin<br> <br> |
| Active Comparator: Glimepirde, Metformin, Dapagliflozin<br>Sodium-glucose cotransporter 2 (SGLT2) inhibitors Dapagliflozin | Drug: Dapagliflozin<br>* 10mg qd per oral during 24months compared with other treatment groups<br>* Other names: Forxiga;Drug: Glimepirde<br> <br> * Other names: Amaryl;Drug: Metformin<br> <br> |
| Active Comparator: Glimepirde, Metformin, Lobeglitazone<br>Peroxisome proliferator-activated receptor gamma agonist Lobeglitazone | Drug: Lobeglitazone<br>* 0.5mg qd per oral during 24months compared with other treatment groups<br>* Other names: Duvie;Drug: Glimepirde<br> <br> * Other names: Amaryl;Drug: Metformin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic target goal achievement rate | HbA1c< 7.0% without hypoglycemia | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell function | Beta-cell function | 6 and 24 months | 
| insulin resistance | insulin resistance | 6 and 24 months | 
| Fasting blood sugar (FBS) and Post Prandial 2 hour blood glucose (PP2) | Fasting blood sugar (FBS) and Post Prandial 2 hour blood glucose (PP2) | 3,6,9,12,16,20 and 24months | 
| Lipid profile | Lipid profile | 3,6,9,12,16,20 and 24months | 
| Body fat | Body fat | 6,12 and 24 months | 
| urine microalbumin to creatinine ratio | urine microalbumin to creatinine ratio | 6,12 and 24 months | 
| Change of HbA1c | Change of HbA1c | 3,6,9,12,16,20 and 24months | 
| Glycemic target goal achievement rate | HbA1c< 7.0% without hypoglycemia | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple combination therapy, sitagliptin, dapagliflozin, lobeglitazone