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

Type 2 Diabetes Clinical Trial

Official title:

Therapeutic Efficacy of Triple Combination of Metformin, DPP4 Inhibitor and Thiazolidinedione in Drug-naïve Korean Type 2 Diabetic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02188186
• Other study ID #: Triple
• Status: Completed
• Phase: Phase 4
• Start date: July 2014
• Est. completion date: September 2018

Study information

• Verified date: March 2019
• Source: Seoul National University Bundang Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• Initial triple combination
Initial triple combination arm
• Conventional treatment
Conventioanl treament with dose escalation

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hypoglycemia	Incidence of hypoglycemia during study period	12 months
Other	Body weight	Changes of body weight after one year treatment	12 months
Other	Body composition	Changes of body composition after one year treatment	12 months
Primary	Change of HbA1c	Therapeutic efficacy of triple combination of metform, sitagliptin, and lobeglitazone compared with sulfonylurea and metformin in drug-naïve Korean type 2 diabetic patients	12 months
Secondary	beta-cell function	Changes of beta-cell function after one year treatment	12 months
Secondary	Insulin resistance	Changes of Insulin resistance after one year treatment	12 months
Secondary	Glucose homeostasis	Changes in fasting glucose concentration	12 months
Secondary	Glucose metabolism	Area under the curve of glucose during OGTT	12 months
Secondary	Glucose metabolism	Area under the curve of insulin during OGTT	12 months
Secondary	Microalbuminuria	urine microalbumin to creatinine ratio	12 months
Secondary	Lipid profile	Changes in TG/HDL/LDL-concentrations	12 months