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

Korea University

Status and phase: Unknown; Phase 3

Conditions: Diabetes Mellitus, Type II

Treatments: Drug: Stepwise add-on therapy; Drug: triple combination therapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02946632

TRIPLE-AXEL-ESR

Details and patient eligibility

About

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.

Full 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.

Enrollment: 104 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 2 patient groups

Triple combination therapy group

Experimental group

Description:

Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks

Treatment:

Drug: triple combination therapy

Stepwise add-on therapy group

Active Comparator group

Description:

* 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

Treatment:

Drug: Stepwise add-on therapy