Clinical trial NCT02315287: Comparison of Lobeglitazone With Pioglitazone as Initial Triple Therapy for Diabetes Management
Official title: Comparison of Therapeutic Efficacy Between Lobeglitazone and Pioglitazone as Initial Triple Therapy With Metformin and Sitagliptin in Drug-naïve Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: Triple combination
Metformin
Sitagliptin
Pioglitazone
Lobeglitazone
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
First posted: 2014-12-11
Enrollment: 190
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Change of HbA1c
timeFrame: 5 and 12 months
Secondary outcomes:
measure: Beta-cell function
timeFrame: 12 months
measure: Insulin resistance
timeFrame: 12 months
measure: HbA1c < 7.0%
timeFrame: 5 and 12 months
measure: HbA1c =< 6.5%
timeFrame: 5 and 12 months
measure: FBS and PP2
timeFrame: 5 and 12 months
measure: microalbumin to creatinine ratio
timeFrame: 5 and 12 months
Other outcomes:
measure: Hypoglycemia
timeFrame: 12 months
measure: Body weight
timeFrame: 12 months
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
Study officials:
affiliation: SNUBH
name: Soo Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: