Therapeutic Efficacy of Triple Combination in Drug-naïve Korean Type 2 Diabetic Patients
Condition: Type 2 Diabetes
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Initial triple combination; Conventional treatment
Intervention type(s): Drug; Drug
Intervention description(s): Initial triple combination arm; Conventioanl treament with dose escalation
Other intervention name(s): metformin+sitagliptin (Januvia)+lobeglitazone (Duvie); metformin+sulfonylurea with dose escalation
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: triple combination; metformin; sitagliptin; thiazolidinedione