Clinical trial NCT05915949: Comparison of Dapagliflozin, Lobeglitazone, and Its Combination in Efficacy and Safety
Official title: Evaluation of the Efficacy of Combination of Dapagliflozin and Lobeglitazone on Glucose Concentrations and Body Fat in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Diabetes Type 2
Keywords: diabetes type 2
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
First posted: 2023-06-23
Enrollment: 99
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: HbA1c
timeFrame: 6 months
Secondary outcomes:
measure: Fasting plasma glucose
timeFrame: 6 months
measure: Postprandial glucose
timeFrame: 6 months
measure: Whole body muscle
timeFrame: 6 months
measure: Whole body fat
timeFrame: 6 months
measure: Abdominal subcutaneous fat
timeFrame: 6 months
measure: Abdominal visceral fat
timeFrame: 6 months
measure: NTproBNP
timeFrame: 6 months
measure: Troponin T
timeFrame: 6 months
measure: Lipids
timeFrame: 6 months
measure: Lipoprotein (a)
timeFrame: 6 months
measure: Urinary microalbumin-Creatinine ratio
timeFrame: 6 months
measure: Fib-4
timeFrame: 6 months
Other outcomes:
measure: Adverse events
timeFrame: 6 months
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
Study officials:
References: