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

Seoul National University

Status and phase: Enrolling; Phase 4

Conditions: Diabetes Type 2

Treatments: Drug: Lobeglitazone 0.5 mg; Drug: Dapagliflozin 10mg Tab; Drug: Dapagliflozin + Lobeglitazone

Study type: Interventional

Funder types: Other

Identifiers

NCT05915949

B-1910-568-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 99 estimated patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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99 participants in 3 patient groups

Dapagliflozin

Experimental group

Description:

Dapagliflozin 10 mg once daily will be given to participants.

Treatment:

Drug: Dapagliflozin 10mg Tab

Lobeglitazone

Active Comparator group

Description:

Lobeglitazone 0.5 mg once daily will be given to participants.

Treatment:

Drug: Lobeglitazone 0.5 mg

Dapagliflozin and Lobeglitazone combined

Active Comparator group

Description:

Dapagliflozin 10 mg and lobeglitazone 0.5 mg once daily together will be given to participants.

Treatment:

Drug: Dapagliflozin + Lobeglitazone