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

NCT ID: NCT02188186

Last Updated: 2019-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-09-30

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Conventional treatment

Intervention Type: DRUG

Conventioanl treament with dose escalation

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.

Group Type: EXPERIMENTAL

Initial triple combination

Intervention Type: DRUG

Initial triple combination arm

Interventions

Initial triple combination

Initial triple combination arm

Intervention Type: DRUG

Conventional treatment

Conventioanl treament with dose escalation

Intervention Type: DRUG

Other Intervention Names

metformin+sitagliptin (Januvia)+lobeglitazone (Duvie); metformin+sulfonylurea with dose escalation

Eligibility 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)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Bundang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Soo Lim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Countries

South Korea

Other Identifiers

Triple

Identifier Type: -

Identifier Source: org_study_id