Comparison of Lobeglitazone With Pioglitazone as Initial Triple Therapy for Diabetes Management
Study Details
Study Description
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. Newly developed thiazolidinedione, Lobeglitazone would be not inferior to Pioglitazone.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Metformin, Sitagliptin, Pioglitazone Thiazolidinedione |
Drug: Pioglitazone
Comparison of two different thiazolidinediones
Other Names:
|
| Active Comparator: Metformin, Sitagliptin, Lobeglitazone Thiazolidinedione |
Drug: Lobeglitazone
Comparison of two different thiazolidinediones
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change of HbA1c [5 and 12 months]
Comparison of therapeutic efficacy of two thiazolidinediones (Piogitazone vs. Lobeglitazone) in drug-naïve Korean type 2 diabetic patients
Secondary Outcome Measures
- Beta-cell function [12 months]
Changes of beta-cell function after 12 months treatment of triple combination
- Insulin resistance [12 months]
Changes of insulin resistance after 12 months treatment of triple combination
- HbA1c < 7.0% [5 and 12 months]
Comparision of glycemic control
- HbA1c =< 6.5% [5 and 12 months]
Comparision of glycemic control
- FBS and PP2 [5 and 12 months]
Comparision of glycemic control
- microalbumin to creatinine ratio [5 and 12 months]
Comparision of albumiuria
Other Outcome Measures
- Hypoglycemia [12 months]
Incidence of hypoglycemia in triple combination treatment
- Body weight [12 months]
Changes of weight after 12months treatment of triple combination
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul National University Bundang Hospital | Seongnam | Gyeonggi | Korea, Republic of | 463-707 |
Sponsors and Collaborators
- Seoul National University Bundang Hospital
Investigators
- Principal Investigator: Soo Lim, MD, PhD, SNUBH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Lobe vs. Pio