Comparison of Dapagliflozin, Lobeglitazone, and Its Combination in Efficacy and Safety (Location-F)

Evaluation of the Efficacy of Combination of Dapagliflozin and Lobeglitazone on Glucose Concentrations and Body Fat in Patients With Type 2 Diabetes

Diabetes is the most frequently occurring chronic disease along with obesity, hypertension, and hyperlipidemia. The number of patients with diabetes is increasing worldwide. Despite rapid progress in management of diabetes, the problem is that glycemic target goal is still low showing 30-40%. Thus, diabetes has become a serious social, economic, and public health problem beyond individual health problems due to its increasing prevalence.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Type 2
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Drug: Lobeglitazone 0.5 mg; Drug: Dapagliflozin + Lobeglitazone

Detailed Description

Previously, metformin, sulfonylurea, and insulin injections were used to treat diabetes, but since then, various new drugs such as thiazolidinedione (TZD), sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitor, and glucagon like peptide-1 (GLP-1) receptor agonist have been released. Among them, metformin and TZD are known to improve insulin resistance, SGLT-2 inhibitor has a mechanism to excrete glucose into urine, and other drugs have a mechanism to promote insulin secretion.

After a report in 2007 that rosiglitazone could increase cardiovascular disease, use of TZD has been limited. However, more people are having insulin resistance, and this is more evident in developing countries. In this circumstance, TZD can be a main stay for diabetic patients with insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ (PPARγ). They have shown excellent glycemic durability. On the other hand, SGLT-2 inhibitors are attracting attention as a mechanism that directly excretes excess glucose in diabetic patients through urine. Many cardiovascular outcome trials have proven its efficacy in cardiovascular and renal outcomes. Current guidelines proposed a new paradigm in the management of T2DM, with a preferential place for SGLT-2 inhibitors, after metformin, in patients with atherosclerotic cardiovascular disease, heart failure and progressive kidney disease.

As such, combination therapy of TZD and SGLT-2 inhibitors, two drugs that have mechanisms for improving insulin resistance and urinary glucose excretion, would have compensatory effects, which would be effective for diabetes treatment. In addition, since studies that investigated effect of TZD and SGLT-2 inhibitor combination on changes in body fat mass and metabolic phenotype are lacking, we investigated the effect of reducing visceral fat (abdominal visceral fat mass/abdominal subcutaneous fat mass) in combination therapy with dapagliflozin, an SGLT-2 inhibitor, and lobeglitazone, a TZD.

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Minji Sohn, PhD; Phone Number: 82-031-787-7041; Email: 65423@snuhb.org

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Soo Lim, MD, PHD; Phone Number: 82-31-787-7035; Email: limsoo@snu.ac.kr
      • Principal Investigator: Soo Lim, MD, PHD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• type 2 diabetic patients between the ages of 20 and 80 who are taking oral diabetes medications (metformin and/or DPP-4 inhibitors) for more than 8 weeks without dose adjustment
• body mass index (BMI) ≥ 20 kg/m2
• eGFR ≥ 50 mL/min/1.73 m2
• HbA1c: 7-10%.

Exclusion Criteria:

• patients with type 1 diabetes; HbA1c <7% or HbA1c >10%
• fasting blood glucose (FPG) >15 mmol/L (270 mg/dL) at the first visit (screening) and pre-randomization screening
• women of childbearing potential (if not using proper contraception)
• history of gastric surgery (including gastric banding within 3 years)
• history of diabetic ketoacidosis or non-ketogenic hyperosmotic coma
• average of 3 blood pressure measurements is systolic blood pressure (SBP) >180 mmHg or diastolic blood pressure (DBP) >100 mmHg
• heart failure NYHA class III or IV
• AST or ALT greater than 3 times the upper limit of normal
• systemic corticosteroids have been used for 10 consecutive days within 90 days (topical, eye drop, topical or inhalation agents)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10 mg once daily will be given to participants.	Drug: Dapagliflozin 10mg Tab; Forxiga 10mg Tab once daily will be given to participants for 24 weeks.; Other Names: Forxiga 10mg
Active Comparator: Lobeglitazone; Lobeglitazone 0.5 mg once daily will be given to participants.	Drug: Lobeglitazone 0.5 mg; Duvie 0.5mg Tab once daily will be given to participants for 24 weeks.; Other Names: Duvie 0.5 mg
Active Comparator: Dapagliflozin and Lobeglitazone combined; Dapagliflozin 10 mg and lobeglitazone 0.5 mg once daily together will be given to participants.	Drug: Dapagliflozin + Lobeglitazone; Duvie 0.5mg Tab once daily will be given to participants for 24 weeks.; Other Names: Forxiga 10mg + Duvie 0.5mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Glycemic control	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose	Glucose metabolism	6 months
Postprandial glucose	Glucose metabolism	6 months
Whole body muscle	Body composition	6 months
Whole body fat	Body composition	6 months
Abdominal subcutaneous fat	Body composition	6 months
Abdominal visceral fat	Body composition	6 months
NTproBNP	Cardiac marker	6 months
Troponin T	Cardiac marker	6 months
Lipids	Lipid profiles (TG, HDL, and LDL)	6 months
Lipoprotein (a)	Lipid metabolism	6 months
Urinary microalbumin-Creatinine ratio	Lipid metabolism	6 months
Fib-4	Hepatic fibrosis marker	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Side effects.	6 months

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): October 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 14, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 23, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: diabetes type 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: B-1910-568-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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