SGLT-2 Inhibitor Effects on Cardiac and Hepatic Metabolic Profiles for the Diabetes Patients Combined With Obesity

National Cheng-Kung University

Status: Completed

Conditions: Fatty Liver Disease

Treatments: Drug: Canagliflozin 100mg

Study type: Interventional

Funder types: Other

Identifiers

NCT05764811

A-BR-108-103

Details and patient eligibility

About

Obesity is closely associated with an increased risk of cardiomyopathy because of the high metabolic activity of excessive fat while effective treatment of obesity-related cardiomyopathy is currently unsolved. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) are a class of diabetic medications. Besides improving glucose control, SGLT2-i has been shown to be able to reduce the bodyweight as well as the mortality and hospitalization rates for heart failure and cardiovascular disease in the type 2 diabetes patients. It has been proposed that the heart protection by SGLT2-i might be caused by modulating the production of adipokine and cytokine. The investigators will enrolled 40 patients (diabetes mellitus with BMI>27 Kg/m2) from obesity weight-reduction clinics: 1) 20 patients treated with SGLT2-i (CANA) and regular weight-reduction plan; 2) 20 patients with regular weight reduction plan, without CANA, for 4 weeks. The investigators will compare the variation of Fibroblast growth factor-21 (FGF21) related proteins and RNA between these 2 groups of subjects. The investigators will arrange cardiac ultrasound, hepatic MRI and fibroscan, body composition dual energy x-ray absorptiometry to evaluate the possible mechanisms underlying the liver and heart modification process, as a scientific basis for precision medicine in the future. Conclusions: SGLT2-i treatment may increase the concentration of FGF21, either in the liver or heart, thus to protect the high-fat diet induced obesity associated heart dysfunction by activating FGF21 downstream protein expression.

Full description

The investigators will enrolled 40 diabetes mellitus with BMI>27 Kg/m2 patients from obesity weight-reduction clinics and will compare the variation of FGF21 related proteins between these 2 groups of subjects. Serial examinations will evaluate the possible mechanisms underlying the protective mechanism. This investigation expect that SGLT2-inhibitor can increase the concentration of FGF21 in the heart by increasing FGF21 in the liver, thereby modifying associated protein expressions and ultimately improving cardiac function and patient outcomes.

Enrollment: 40 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age> 20 years of age
2. With diagnosis of diabetic mellitus (HbA1C≧6.5%) by medical record or physicians
3. BMI ≧ 27 kg/m2, which is the current definition of obesity from Health Promotion Administration, Ministry of Health and Welfare.

Exclusion criteria

1. Unwilling to participating current clinical trial
2. Cannot tolerate SGLT2-i therapy
3. Not willing to join the study
4. History of failure treatment experience from SGLT2-i or other weight reduction plan
5. Received pharmaceutical or clinical trials within past 1 year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 2 patient groups

Canagliflozin Treatment

Active Comparator group

Description:

Use Canagliflozin 100 mg daily, 1 month

Treatment:

Drug: Canagliflozin 100mg

non-Canagliflozin Treatment

No Intervention group

Description:

Standard treatment