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

Mechanism of the Effect by Sodium-glucose Cotransporter-2 Inhibitor on Obesity Associated Cardiomyopathy

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.

Study Overview

• Status: Completed
• Conditions: Fatty Liver Disease
• Intervention / Treatment: Drug: Canagliflozin 100mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Canagliflozin Treatment; Use Canagliflozin 100 mg daily, 1 month	Drug: Canagliflozin 100mg; 100 mg daily for a month; Other Names: standard of care
No Intervention: non-Canagliflozin Treatment; Standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measure the severity of fatty liver via MRI	The fibrotic score and severity by MRI of the liver will be performed before and after the treatment. The measurement of fatty liver requires both in-phase (IP) and out-of-phase (OOP) imaging to be adequately assessed. Fatty liver appears: T1: hyperintense, T2: mildly hyperintense, IP/OOP imaging: signal drop out on OOP imaging On IP/OOP imaging, signal loss is demonstrated when there is 10-15% fat fraction with maximum signal loss occurring when there is 50% fatty infiltration of the liver. In situations in which there is >50% fatty infiltration, the out-of-phase sequence paradoxically becomes less hypointense than at 50%.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measure the body weight before and after the treatment	check the status of body weight (kilograms) before and after treatment	4 weeks
measure the body height before and after the treatment	check the status of body height (metres) before and after treatment	4 weeks
measure the body mass index (BMI) before and after the treatment	compare BMI before and after treatment; BMI is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and height in metres.	4 weeks

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Investigators: Study Director: Ping-Yen Liu, National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: fatty liver; diabetes mellitus; SGLT2 inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: A-BR-108-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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