Comparison of Dapagliflozin, Lobeglitazone, and Its Combination in Efficacy and Safety

Diabetes Type 2 Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05915949
• Other study ID #: B-1910-568-001
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2023
• Source: Seoul National University Bundang Hospital
• Contact: Minji Sohn, PhD
• Phone: 82-031-787-7041
• Email: 65423[@]snuhb.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: December 31, 2023
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetes Type 2

Intervention

Drug:
• Dapagliflozin 10mg Tab
Forxiga 10mg Tab once daily will be given to participants for 24 weeks.
• Lobeglitazone 0.5 mg
Duvie 0.5mg Tab once daily will be given to participants for 24 weeks.
• Dapagliflozin + Lobeglitazone
Duvie 0.5mg Tab once daily will be given to participants for 24 weeks.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Side effects.	6 months
Primary	HbA1c	Glycemic control	6 months
Secondary	Fasting plasma glucose	Glucose metabolism	6 months
Secondary	Postprandial glucose	Glucose metabolism	6 months
Secondary	Whole body muscle	Body composition	6 months
Secondary	Whole body fat	Body composition	6 months
Secondary	Abdominal subcutaneous fat	Body composition	6 months
Secondary	Abdominal visceral fat	Body composition	6 months
Secondary	NTproBNP	Cardiac marker	6 months
Secondary	Troponin T	Cardiac marker	6 months
Secondary	Lipids	Lipid profiles (TG, HDL, and LDL)	6 months
Secondary	Lipoprotein (a)	Lipid metabolism	6 months
Secondary	Urinary microalbumin-Creatinine ratio	Lipid metabolism	6 months
Secondary	Fib-4	Hepatic fibrosis marker	6 months