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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

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Initial triple combination Drug: Conventional treatment Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Efficacy of Triple Combination of Metformin, DPP4 Inhibitor and Thiazolidinedione in Drug-naïve Korean Type 2 Diabetic Patients
Actual Study Start Date : July 2014
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Drug: Conventional treatment
Conventioanl treament with dose escalation
Other Name: metformin+sulfonylurea with dose escalation

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.

Drug: Initial triple combination
Initial triple combination arm
Other Name: metformin+sitagliptin (Januvia)+lobeglitazone (Duvie)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. beta-cell function [ Time Frame: 12 months ]
    Changes of beta-cell function after one year treatment

  2. Insulin resistance [ Time Frame: 12 months ]
    Changes of Insulin resistance after one year treatment

  3. Glucose homeostasis [ Time Frame: 12 months ]
    Changes in fasting glucose concentration

  4. Glucose metabolism [ Time Frame: 12 months ]
    Area under the curve of glucose during OGTT

  5. Glucose metabolism [ Time Frame: 12 months ]
    Area under the curve of insulin during OGTT

  6. Microalbuminuria [ Time Frame: 12 months ]
    urine microalbumin to creatinine ratio

  7. Lipid profile [ Time Frame: 12 months ]
    Changes in TG/HDL/LDL-concentrations


Other Outcome Measures:
  1. Hypoglycemia [ Time Frame: 12 months ]
    Incidence of hypoglycemia during study period

  2. Body weight [ Time Frame: 12 months ]
    Changes of body weight after one year treatment

  3. Body composition [ Time Frame: 12 months ]
    Changes of body composition after one year treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188186


Locations
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Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, Gyeonggi, Korea, Republic of, 463-707
Sponsors and Collaborators
Seoul National University Bundang Hospital
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Responsible Party: Soo Lim, Professor, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier: NCT02188186    
Other Study ID Numbers: Triple
First Posted: July 11, 2014    Key Record Dates
Last Update Posted: March 18, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Soo Lim, Seoul National University Bundang Hospital:
triple combination
metformin
sitagliptin
thiazolidinedione
Additional relevant MeSH terms:
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Metformin
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action