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

Phase 4

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Conventional treatment; Drug: Initial triple combination

• Registration Number: NCT02188186
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-07-07
• Study First Submitted QC: 2014-07-10
• Study First Posted: 2014-07-11
• Primary Completion: 2018-09
• Study Completion: 2018-09
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-14
• Last Update Posted: 2019-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional treatment	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.
Initial triple combination treatment	Initial triple combination	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.

Primary Outcome Measures

Name	Time	Method
Change of HbA1c	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

Name	Time	Method
Glucose homeostasis	12 months	Changes in fasting glucose concentration
Lipid profile	12 months	Changes in TG/HDL/LDL-concentrations
beta-cell function	12 months	Changes of beta-cell function after one year treatment
Glucose metabolism	12 months	Area under the curve of insulin during OGTT
Insulin resistance	12 months	Changes of Insulin resistance after one year treatment
Microalbuminuria	12 months	urine microalbumin to creatinine ratio

Trial Locations

Locations (1)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Gyeonggi, Korea, Republic of