Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes

Study Overview
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Brief Summary
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In this study, the investigators will assess the efficacy and tolerability of a novel, initial triple combination therapy with metformin, saxaglipitin, and dapagliflozin, compared to conventional stepwise add-on therapy in drug-naïve patients with recently onset type 2 diabetes.

Detailed Description
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ADA/EASD guideline recommends sequential treatment approach starting with metformin, and adding other classes of anti-diabetic medications if target HbA1c is not achieved. However, several clinical studies clearly showed that initial dual or triple combination therapy was more favorable in terms of glycemic control. A DPP-4 inhibitor saxagliptin increases serum level of GLP-1, and potentiates its action of increasing glucose-dependent insulin secretion and lowering glucagon secretion. A SGLT-2 inhibitor dapagliflozin lowers hyperglycemia via blocking SGLT-2 to increase glucosuria, that is, in an insulin-independent manner. Therefore, the mechanism of action of these drugs are complimentary to that of metformin, and all of these have a low risk of hypoglycemia and weight gain.

Official Title
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Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type II

Intervention / Treatment
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* Drug: triple combination therapy
* Drug: Stepwise add-on therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Drug-naïve patients with type 2 diabetes by American Diabetes Association criteria HbA1c ≥ 8%, < 10.5% at screening Age ≥ 18 years, < 65 years Body mass index (BMI) ≥ 23 kg/m2, < 35 kg/m2 Estimated GFR (eGFR) ≥ 60 ml/min/1.73m2 Exclusion Criteria: Uncontrolled hyperglycemia > 270 mg/dl after an overnight fast Diabetic ketoacidosis Type 1 diabetes Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening Congestive heart failure (New York Heart Association functional class IV) severe hepatic dysfunction (serum levels of either AST, ALT, or alkaline phosphatase above 3 x upper limit of normal (ULN)) alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women use of systemic glucocorticoid

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple combination therapy group<br>Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks | Drug: triple combination therapy<br>* Xigduo (metformin 1000mg + dapagliflozin 10mg) saxagliptin 5mg<br>* Other names: saxagliptin 5mg;|
| Active Comparator: Stepwise add-on therapy group<br>Participants were started on metformin 1000mg once daily after screening & assignment At each visits, FPG and HbA1c are measured. Sequential add-on therapy regimen is described | Drug: Stepwise add-on therapy<br>* metformin -> glimepirde -> sitagliptin<br>* Other names: Sitagliptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks |  | 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks |  | 52 weeks | 
| Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks |  | 104 weeks | 
| Change in body HbA1c from baseline to week 104 |  | 104 weeks | 
| Change in body weight from baseline to week 104 |  | 104 weeks | 
| Change in systolic blood pressure from baseline to week 104 |  | 104 weeks | 
| Changes in fat and lean mass from baseline to at 104 weeks |  | 104 weeks |