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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02946632
Recruitment Status : Not yet recruiting
First Posted : October 27, 2016
Last Update Posted : October 27, 2016
Information provided by (Responsible Party):
Sin Gon Kim, Korea University Anam Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type II Drug: triple combination therapy Drug: Stepwise add-on therapy Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Triple combination therapy group
Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks
Drug: triple combination therapy
Xigduo (metformin 1000mg + dapagliflozin 10mg) saxagliptin 5mg
Other Names:
  • metformin 1000mg
  • dapagliflozin 10mg
  • saxagliptin 5mg

Active Comparator: Stepwise add-on therapy group
  • 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
metformin -> glimepirde -> sitagliptin
Other Names:
  • Metformin
  • Glimepiride
  • Sitagliptin

Primary Outcome Measures :
  1. Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks [ Time Frame: 104 weeks ]

Secondary Outcome Measures :
  1. ∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks [ Time Frame: 52 weeks ]
  2. Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks [ Time Frame: 104 weeks ]
  3. Change in body HbA1c from baseline to week 104 [ Time Frame: 104 weeks ]
  4. Change in body weight from baseline to week 104 [ Time Frame: 104 weeks ]
  5. Change in systolic blood pressure from baseline to week 104 [ Time Frame: 104 weeks ]
  6. Changes in fat and lean mass from baseline to at 104 weeks [ Time Frame: 104 weeks ]

Other Outcome Measures:
  1. AEs/SAEs [ Time Frame: 104 weeks ]

    hypoglycemia, GI trouble, urinary tract infection, genital infection, volume depletion, panreatitis, severe cutaneous events, hypersensitivity reactions)

    • Vital signs
    • Collection of clinical chemistry/haematology parameters

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02946632

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Contact: SinGon Kim, MD 010-4191-0958

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Korea, Republic of
Korea University Anam Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Korea University Anam Hospital
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Principal Investigator: SinGon Kim, MD 'Korea University Anam Hospital' in Seoul, Korea

Publications of Results:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sin Gon Kim, Professor, Korea University Anam Hospital Identifier: NCT02946632     History of Changes
Other Study ID Numbers: TRIPLE-AXEL-ESR
First Posted: October 27, 2016    Key Record Dates
Last Update Posted: October 27, 2016
Last Verified: October 2016
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Sodium-Glucose Transporter 2 Inhibitors