Clinical trial NCT02946632: Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diabetes Mellitus, Type II
Lead sponsor: Korea University Anam Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2016-10-27
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks
timeFrame: 104 weeks
Secondary outcomes:
measure: ∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks
timeFrame: 52 weeks
measure: Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks
timeFrame: 104 weeks
measure: Change in body HbA1c from baseline to week 104
timeFrame: 104 weeks
measure: Change in body weight from baseline to week 104
timeFrame: 104 weeks
measure: Change in systolic blood pressure from baseline to week 104
timeFrame: 104 weeks
measure: Changes in fat and lean mass from baseline to at 104 weeks
timeFrame: 104 weeks
Other outcomes:
measure: AEs/SAEs
timeFrame: 104 weeks
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
Study officials:
affiliation: 'Korea University Anam Hospital' in Seoul, Korea
name: SinGon Kim, MD
role: PRINCIPAL_INVESTIGATOR
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