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Therapeutic Efficacy of Triple Combination in Drug-naïve Korean Type 2 Diabetic Patients

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ClinicalTrials.gov Identifier: NCT02188186
Recruitment Status : Completed
First Posted : July 11, 2014
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
Soo Lim, Seoul National University Bundang Hospital

Tracking Information
First Submitted Date  ICMJE July 7, 2014
First Posted Date  ICMJE July 11, 2014
Last Update Posted Date March 18, 2019
Actual Study Start Date  ICMJE July 2014
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2017)
Change of HbA1c [ Time Frame: 12 months ]
Therapeutic efficacy of triple combination of metform, sitagliptin, and lobeglitazone compared with sulfonylurea and metformin in drug-naïve Korean type 2 diabetic patients
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2014)
Change of HbA1c [ Time Frame: 12 months ]
Therapeutic efficacy of triple combination of metformin, sitagliptin and thiazolidinedione in drug-naïve Korean type 2 diabetic patients
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2017)
  • beta-cell function [ Time Frame: 12 months ]
    Changes of beta-cell function after one year treatment
  • Insulin resistance [ Time Frame: 12 months ]
    Changes of Insulin resistance after one year treatment
  • Glucose homeostasis [ Time Frame: 12 months ]
    Changes in fasting glucose concentration
  • Glucose metabolism [ Time Frame: 12 months ]
    Area under the curve of glucose during OGTT
  • Glucose metabolism [ Time Frame: 12 months ]
    Area under the curve of insulin during OGTT
  • Microalbuminuria [ Time Frame: 12 months ]
    urine microalbumin to creatinine ratio
  • Lipid profile [ Time Frame: 12 months ]
    Changes in TG/HDL/LDL-concentrations
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2014)
  • beta-cell function [ Time Frame: 12 months ]
    Changes of beta-cell function after one year treatment of triple combination
  • Insulin resistance [ Time Frame: 12 months ]
    Changes of Insulin resistance after one year treatment of triple combination
Current Other Pre-specified Outcome Measures
 (submitted: October 6, 2017)
  • Hypoglycemia [ Time Frame: 12 months ]
    Incidence of hypoglycemia during study period
  • Body weight [ Time Frame: 12 months ]
    Changes of body weight after one year treatment
  • Body composition [ Time Frame: 12 months ]
    Changes of body composition after one year treatment
Original Other Pre-specified Outcome Measures
 (submitted: July 10, 2014)
  • Hypoglycemia [ Time Frame: 12 months ]
    Incidence of hypoglycemia in triple combination treatment
  • Body weight [ Time Frame: 12 months ]
    Changes of body weight after one year treatment of triple combination
 
Descriptive Information
Brief Title  ICMJE Therapeutic Efficacy of Triple Combination in Drug-naïve Korean Type 2 Diabetic Patients
Official Title  ICMJE Therapeutic Efficacy of Triple Combination of Metformin, DPP4 Inhibitor and Thiazolidinedione in Drug-naïve Korean Type 2 Diabetic Patients
Brief Summary Triple combination of metformin, DPP4 inhibitor and Thiazolidinedione would be a good option in the treatment of drug-naïve Korean type 2 diabetic patients.
Detailed Description

Thiazolidionedione, a PPARgamman agonist, is an strong insulin sensitizer. It has shown that durable glucose lowering effect and beta cell preservation. It is an important treatment option in patients with type 2 diabetes.

It has been well established that inhibition of dipeptidyl peptidase-4 (DPP-4) reduces blood glucose levels in both fasting and postprandial states, and preserves pancreatic β-cell function in patients with type 2 diabetes. The mechanism of action of DPP-4 inhibitors is to increase levels of active incretin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion as well as insulin biosynthesis while inhibiting glucagon release from pancreatic islets.

DPP4 inhibitors also have better safety and tolerability profiles (e.g., weight neutrality and less hypoglycemia) compared to other hypoglycemic agents. When considering combination therapy with DPP-4 inhibitors, metformin is the most commonly used agent which has been shown to be effective and well tolerated from previous studies. Besides the glucose lowering effect by reducing hepatic glucose output and improving insulin resistance, metformin without inhibiting DPP-4 activity,also increases active GLP-1 concentrations by 1.5- to 2-fold following an oral glucose load in obese, nondiabetic subjects. Accordingly, this effect of metformin may provide a unique benefit when combined with DPP-4 inhibitors through a substantial enhancement of the incretin axis, which provides effective and potentially additive glycemic improvement.

Because of its favorable pharmacological properties, combination of a DPP-4 inhibitor, metformin, and thiazolidinedione has been increasingly used to achieve rapid glycemic goal with low risk of hypoglycemia and no weight gain, and to delay the need for subsequent regimen changes. DPP-4 inhibitors block DPP-4 enzyme and preserve endogenous incretins whereas metformin increases the active form of GLP-1, both of which may enhance the secretory function of pancreas. However, the response to DPP-4 inhibitors and metformin combination therapy may be different in individuals according to their pancreatic function and insulin resistance status. In fact, previous studies with DPP-4 inhibitors showed different potency in glycemic controls depending on various patient characteristics including severity of diabetes and the use of other antidiabetic drug.Consequently, it would be clinically important to investigate effect of this triple combination therapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes
Intervention  ICMJE
  • Drug: Initial triple combination
    Initial triple combination arm
    Other Name: metformin+sitagliptin (Januvia)+lobeglitazone (Duvie)
  • Drug: Conventional treatment
    Conventioanl treament with dose escalation
    Other Name: metformin+sulfonylurea with dose escalation
Study Arms  ICMJE
  • Active Comparator: Conventional treatment

    Initial dual combination therapy with sulfonylurea and metfomin. Dose of sulfonylurea (glimepride 2-8 mg) and metfomin (500-2550 mg) can be ecalated at investigator's discreition at every visit.

    Insulin therpy can be added as a rescue therapy at investigator's discreition.

    Intervention: Drug: Conventional treatment
  • Experimental: Initial triple combination treatment

    Initial dual combination therapy with metformin, sitagliptin (Januvia 100 mg), and lobeglitazone (Duvie 0.5 mg).

    Insulin therpy can be added as a rescue therapy at investigator's discreition.

    Intervention: Drug: Initial triple combination
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 6, 2017)
200
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2014)
50
Actual Study Completion Date  ICMJE September 2018
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HbA1c 9-12%
  • No treatment with insulin or oral agents for recent 6 months
  • 20 ≤ Age < 80 years

Exclusion Criteria:

  • Contraindication to sitagliptin or metformin or thiazolidinedione
  • Pregnant or breast feeding women
  • Type 1 diabetes, gestational diabetes, or secondary forms of diabetes
  • Not appropriate for oral antidiabetic agent
  • Medication which affect glycemic control
  • Disease which affect efficacy and safety of drugs
  • Any major illness (Liver disease, Renal failure, Heart disease, Cancer, etc)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02188186
Other Study ID Numbers  ICMJE Triple
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Soo Lim, Seoul National University Bundang Hospital
Study Sponsor  ICMJE Seoul National University Bundang Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Seoul National University Bundang Hospital
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP