Diabetes Mellitus, Type II
Conditions
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.
Interventions
Xigduo (metformin 1000mg + dapagliflozin 10mg) saxagliptin 5mg
DRUGStepwise add-on therapy
metformin -\> glimepirde -\> sitagliptin
Sponsors
AstraZeneca
Korea University Anam Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 systolic blood pressure from baseline to week 104 | 104 weeks |
| Changes in fat and lean mass from baseline to at 104 weeks | 104 weeks |
| Change in body weight from baseline to week 104 | 104 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| AEs/SAEs | 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 |
Countries
South Korea
Contacts
Primary ContactSinGon Kim, MD
Outcome results
None listed