Korean Study on Safety and Effectiveness of OAD Triple Therapy in Type 2 Diabetes (TRIO)

A Multicenter, Prospective, Non-interventional Observation Study to Evaluate the Safety and Effectiveness of OAD Triple Therapy in Korean Type 2 Diabetic Mellitus Patients

A multicenter, prospective, non-interventional observation study to evaluate the safety and effectiveness of OAD triple therapy in Korean Type 2 diabetic mellitus patients.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: SGLT2 inhibitor; Drug: DPP-4 inhibitor; Drug: Thiazolidinedione

Detailed Description

The study was designed as a multicenter, prospective, non-interventional, observational study in patients with type 2 diabetes mellitus who had inadequate glycemic control with conventional combination oral hypoglycemic agents including metformin.

Participants in this study will have type 2 diabetes mellitus with insufficient glycemic control on conventional combination therapy with a DPP-4i or SGLT2i oral hypoglycemic agent, including metformin, requiring the addition of one of the following: SGLT-2i, DPP-4i, or TZD.

The 3-drug combination therapy will be prescribed to subjects based on the medical judgment of the investigator based on the licensure of SGLT-2i, DPP-4i, or TZD(efficacy, dosing, precautions for use, etc.) in a real-world practice setting and all treatment and observation, including administration of medications and laboratory tests, will be based on the medical judgment of the investigator.

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Soo Lim, M.D, Ph.D.; Phone Number: 82-2-6373-0773; Email: limsoo@snu.ac.kr

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Soo Lim, M.D, Ph.D.; Phone Number: 1588-3369; Email: limsoo@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with type 2 diabetes mellitus whose glycemic control is inadequate on 2 oral hypoglycemic agents, including metformin.

Description

Inclusion Criteria:

1. Patients with type 2 diabetes who are 19 years of age or older at the time of enrollment.
2. Continued DPP-4i or SGLT-2i oral hypoglycemic combination therapy with metformin for at least 8 weeks prior to enrollment.
3. 7.0% ≤ HbA1c < 10.0% based on laboratory tests performed within 4 weeks of enrollment.
4. Voluntarily give written informed consent after being told about the study.

Exclusion Criteria:

1. Patients with type 1 diabetes and secondary diabetes.
2. Patients receiving concomitant therapy with 3 or more oral hypoglycemic agents within 8 weeks of enrollment.
3. Requiring treatment with insulin, GLP-1, etc. in addition to oral hypoglycemic agents during the study.
4. End-stage renal disease and hemodialysis patients.
5. diabetic ketoacidosis Patients.
6. Pregnant and lactating women.
7. Patients who are contraindicated by any of the "Precautions for Use" in the license for the drug being administered during the study, given the observational nature of the study under routine practice.
8. Patients with a history of hypersensitivity to the investigational drug or any of its components or excipients.
9. Anyone else deemed by the investigator to be unsuitable for participation in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Metformin/DPP4i/SGLT2i; Metformin + DPP4i 2-drug combination plus one of the SGLT-2i class of drugs.	Drug: SGLT2 inhibitor; SGLT2 inhibitor class of drugs; Drug: DPP-4 inhibitor; DPP4 inhibitor class of drugs
Metformin/DPP4i/TZD; Metformin + DPP4i 2-drug combination plus one of the TZD class of drugs.	Drug: DPP-4 inhibitor; DPP4 inhibitor class of drugs; Drug: Thiazolidinedione; Thiazolidinedione class of drugs
Metformin/SGLT2i/DPP4i; Metformin + SGLT2i 2-drug combination plus one of the DPP4i class of drugs.	Drug: SGLT2 inhibitor; SGLT2 inhibitor class of drugs; Drug: DPP-4 inhibitor; DPP4 inhibitor class of drugs
Metformin/SGLT2i/TZD; Metformin + SGLT2i 2-drug combination plus one of the TZD class of drugs.	Drug: SGLT2 inhibitor; SGLT2 inhibitor class of drugs; Drug: Thiazolidinedione; Thiazolidinedione class of drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Incidence of Adverse events in Triple Combination Therapy Including Metformin with SGLT-2i, DPP-4i, or TZD Class Drugs.	Safety assessment of triple combination therapy with Metformin SGLT2i or DPP4i and TZD class drugs(All adverse events occurring after the date of registration).	24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HbA1c	Evaluation of HbA1c(%) Change Compared to Baseline in Each Combination Group	3, 6, (9), 12, 18, and 24 months
Changes in FPG	Evaluation of FPG(mg/dL) Change Compared to Baseline in Each Combination Group	3, 6, (9), 12, 18, and 24 months
Percentage of Subjects with HbA1c < 7.0%	Percentage of Subjects with HbA1c < 7.0% in Each Combination Group	3, 6, (9), 12, 18, and 24 months
Percentage of Subjects with HbA1c < 6.5%	Percentage of Subjects with HbA1c < 6.5% in Each Combination Group	3, 6, (9), 12, 18, and 24 months
Factors influencing HbA1c change at each endpoint for each combination group.	demographics, past hypoglycemic medications, hypoglycemic medication components and doses, duration of hypoglycemic medication, duration of disease, comorbidities, concomitant medications, etc.	24 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Weight	Changes in Weight(kg) Compared to Baseline in Each Combination Group	3, 6, (9), 12, 18, 24 months
Changes in waist circumference	Changes in waist circumference(cm) compared to Baseline in Each Combination Group (body composition in body water(L), protein(kg), minerals(kg), and body fat(kg))	12 and 24 months
Changes in Fatty Liver Index	Changes in Fatty Liver Index compared to Baseline in Each Combination Group	6, 12, 18, and 24 months
Changes in AST	Changes in AST(IU/L) Compared to Baseline in Each Combination Group	6, 12, 18, and 24 months
Changes in ALT	Changes in ALT(IU/L) Compared to Baseline in Each Combination Group	6, 12, 18, and 24 months
Changes Platelet Levels	Changes in Platelet(10^3/uL) Levels Compared to Baseline in Each Combination Group	6, 12, 18, and 24 months
Changes in Blood Lipid Levels(Total cholesterol, LDL-C, HDL-C, TG)	Change in Total cholesterol, LDL-C, HDL-C, TG(mg/dL) compared to Baseline in Each Combination Group	6, 12, 18, and 24 months
Changes in Insulin-Related Test Levels(HOMA-IR, HOMA-β)	Changes in HOMA-IR(%), HOMA-(%) compared to Baseline in Each Combination Group	12 and 24 months
Changes in eGFR	Changes in eGFR(mL/min/1.73m2) compared to Baseline in Each Combination Group	12 and 24 months
Changes in UACR	Changes in UACR(mg/g) compared to Baseline in Each Combination Group	12 and 24 months
Change in hsCRP	Change in hsCRP(mg/dL) compared to Baseline in Each Combination Group	12 and 24 months
Change in ProBNP(or NT-ProBNP)	Change in ProBNP(or NT-ProBNP)(pg/mL) compared to Baseline in Each Combination Group	12 and 24 months
Change in PP2 Compared to Baseline in Each Combination Group	Change in PP2(mg/dL) compared to Baseline in Each Combination Group.	3, 6, (9), 12, 18, and 24 months
Incidence Rate of Major Adverse Cardiovascular Events(MACE)	Incidence Rate of Major Adverse Cardiovascular Events(MACE) from Baseline to 24 Months for Each Combination Group	24 month
Incidence Rate of Diabetic Microvascular Events	Incidence Rate of Diabetic Microvascular Events from Baseline to 24 Months for Each Combination Group	24 month

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 30, 2024
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Observational study; Korean patients; OAD triple therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Protease Inhibitors; Enzyme Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; 2,4-thiazolidinedione; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: D141_01DM2303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No