Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes
- Conditions
- Diabetes Mellitus, Type II
- Interventions
- Drug: triple combination therapyDrug: Stepwise add-on therapy
- Registration Number
- NCT02946632
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 104
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triple combination therapy group triple combination therapy Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks Stepwise add-on therapy group Stepwise add-on therapy * 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
- Primary Outcome Measures
Name Time Method 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
Name Time Method ∙ 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
Trial Locations
- Locations (1)
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of