Comparison of Lobeglitazone With Pioglitazone as Initial Triple Therapy for Diabetes Management

Comparison of Therapeutic Efficacy Between Lobeglitazone and Pioglitazone as Initial Triple Therapy With Metformin and Sitagliptin in Drug-naïve Type 2 Diabetic Patients

Triple combination of metformin, DPP4 inhibitor and Thiazolidinedione would be a good option in the treatment of drug-naïve Korean type 2 diabetic patients. Newly developed thiazolidinedione, Lobeglitazone would be not inferior to Pioglitazone.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Pioglitazone; Drug: Lobeglitazone

Detailed Description

Thiazolidionedione, a PPARgamma 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: Interventional
• Enrollment (Anticipated): 190
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Soo Lim, MD, PHD; Phone Number: 82-31-787-7035; Email: limsoo@snu.ac.kr
• Study Contact Backup: Name: Eu Jeong Ku, MD; Phone Number: 82-31-787-6232; Email: eujeong.ku@gmail.com

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Soo Lim, MD, PHD; Phone Number: 82-31-787-7035; Email: limsoo@snu.ac.kr
      • Principal Investigator: Soo Lim, MD, PHD
      • Contact: Eu Jeong Ku, MD; Phone Number: 82-31-787-6232; Email: eujeong.ku@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HbA1c > 13.0 %
• No treatment with insulin or oral agents for 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin, Sitagliptin, Pioglitazone; Thiazolidinedione	Drug: Pioglitazone; Comparison of two different thiazolidinediones; Other Names: Actos
Active Comparator: Metformin, Sitagliptin, Lobeglitazone; Thiazolidinedione	Drug: Lobeglitazone; Comparison of two different thiazolidinediones; Other Names: Duvie

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of HbA1c	Comparison of therapeutic efficacy of two thiazolidinediones (Piogitazone vs. Lobeglitazone) in drug-naïve Korean type 2 diabetic patients	5 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell function	Changes of beta-cell function after 12 months treatment of triple combination	12 months
Insulin resistance	Changes of insulin resistance after 12 months treatment of triple combination	12 months
HbA1c < 7.0%	Comparision of glycemic control	5 and 12 months
HbA1c =< 6.5%	Comparision of glycemic control	5 and 12 months
FBS and PP2	Comparision of glycemic control	5 and 12 months
microalbumin to creatinine ratio	Comparision of albumiuria	5 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia	Incidence of hypoglycemia in triple combination treatment	12 months
Body weight	Changes of weight after 12months treatment of triple combination	12 months

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Soo Lim, MD, PhD, SNUBH

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimate): December 11, 2014

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 29, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Metformin; Sitagliptin; Pioglitazone; Triple combination; Lobeglitazone
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: Lobe vs. Pio