Overview

Quadruple Oral Combination Therapy for Type 2 Diabetes Mellitus : Glycemic Control by Thiazolidinedione (TZD) or Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitor as an add-on Therapy in Type 2 Diabetes Mellitus After Failure of an Oral Triple Anti

Status:
Completed
Trial end date:
2020-05-28
Target enrollment:
0
Participant gender:
All
Summary
In the treatment of type 2 diabetes (T2D), the number of patients requiring combination therapy of oral antidiabetic agents (OADs) is more than 70%. Especially in Korea, the tendency to avoid insulin therapy is relatively higher than other countries, therefore, the need for combination therapy of OADs is quite high. However, according to the current guidelines, clinicians are recommended to prescribe three or fewer OADs as the combination therapy for T2D. Recently, various OADs have been developed, and it is expected that quadruple combination therapy of OADs would be quite effective to lower blood glucose levels. In the present study, the investigators designed the study to compare the efficacy and safety of quadruple combination therapy; thiazolidinedione (TZD) vs. SGLT-2 inhibitor as an add-on therapy to triple combination therapy (Metformin, Sulfonylurea, Dipeptidyl peptidase-4(DPP-4) inhibitors). Quadruple combination therapy group with the SGLT-2 inhibitor will be considered as active control group, because it have shown non-inferior glycemic efficacy to the conventional insulin conversion therapy in a previous clinical study. Patients who could not achieve the target blood glucose level (7% Phase: Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Yonsei University
Treatments:
2,4-thiazolidinedione
Dipeptidyl-Peptidase IV Inhibitors
Empagliflozin
Hypoglycemic Agents
Metformin
Pioglitazone
Criteria
Inclusion Criteria:

- 1. 19 ≤ age ≤ 80, male or female

- 2. Type 2 diabetes patients who have taken triple combination therapy of OADs as
followed : Metformin (≥1000 mg/day), Sulfonylurea (Glimepiride ≥ 4 mg/day or
Gliclazide ≥ 60 mg/day), DPP-4 inhibitor (Full dose) for over 12 weeks

- 3. At screening, 7% < HbA1c ≤ 10%

- 4. Patients who refused insulin therapy.

- 5. Subjects who understood the contents of the clinical trial and are cooperative in
the trial progress, and are considered to be able to participate until the end of the
trial.

- 6. Patients who have voluntarily agreed in writing to participate in the clinical
trial after hearing the explanation of the trial.

Exclusion Criteria:

- 1. Type 1 diabetes, gestational diabetes, and other types of diabetes than type 2
diabetes mellitus.

- 2. Patients who have the history of allergy of hypersensitivity for the medication of
the clinical trial.

- 3. Patients who have the history of taking TZDs or SGLT-2 inhibitors within a year
prior to screening visit, or have the history of discontinuation of them due to severe
side effects.

- 4. Patients who have the history of acute or chronic metabolic acidosis including
diabetic ketoacidosis (with or without coma), or any kinds of ketosis within 12 weeks
prior to screening visit.

- 5. Patients who have genetic metabolic diseases, such as galactose intolerance, Lapp
lactase deficiency, or glucose-galactose malabsorption

- 6. Patients who have the history of taking steroids for more than 2 weeks, within 8
weeks prior to screening visit.

- 7. Patients who have the history of malignancy within 5 years prior to screening visit
(In case of bladder cancer, subjects will be excluded regardless of the time of
diagnosis)

- 8. Patients who have the history of coronary artery bypass surgery or percutaneous
coronary intervention, or suffered from heart failure (NYHA class III, IV)

- 9. Patients who have the history of uncontrolled arrhythmia, unstable angina,
myocardial infarction, stroke, transient ischemic attacks, and cerebral vascular
disease within 24 weeks prior to the screening date.

- 10. Patients of chronic renal failure, chronic kidney disease stage 3~5 (estimated
glomerular filtration rate calculated vial CKD-EPI <60 mL/min/1.73m2) or on dialysis
therapy.

- 11. Elevated liver enzymes (AST, ALT, ALP ≥ 2.5*upper limit of normal (ULN) or Total
bilirubin ≥ 2.5*ULN) or Child-Pugh class B or C (for the patients of liver cirrhosis)

- 12. Subjects who are pregnant or lactating

- 13. Perioperative patients, patients with severe infections or severe trauma

- 14. Patients with unexamined gross hematuria

- 15. Any other subjects who is determined to be ineligible for the clinical trials by
researchers.