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

October 26, 2016 updated by: Sin Gon Kim, Korea University Anam Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

104

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
  • Sitagliptin
  • Glimepiride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
104 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
∙ 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
52 weeks
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
104 weeks
Change in body HbA1c from baseline to week 104
Time Frame: 104 weeks
104 weeks
Change in body weight from baseline to week 104
Time Frame: 104 weeks
104 weeks
Change in systolic blood pressure from baseline to week 104
Time Frame: 104 weeks
104 weeks
Changes in fat and lean mass from baseline to at 104 weeks
Time Frame: 104 weeks
104 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
104 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University Anam Hospital

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: SinGon Kim, MD, 'Korea University Anam Hospital' in Seoul, Korea

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2016

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

October 25, 2016

First Submitted That Met QC Criteria

October 26, 2016

First Posted (Estimate)

October 27, 2016

Study Record Updates

Last Update Posted (Estimate)

October 27, 2016

Last Update Submitted That Met QC Criteria

October 26, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRIPLE-AXEL-ESR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetes Mellitus, Type II

Clinical Trials on triple combination therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Rwanda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe