The Effects of SGLTi on Diabetic Cardiomyopathy (SGLTi)

The Effects of SGLT Inhibition on Diabetic Cardiomyopathy

Diabetic cardiomyopathy is associated with significant morbidity and mortality. It is considered as a cardiac muscle disorder secondary to diabetes mellitus (DM). Certain studies show the clinical benefit of SGLT-s inhibitors on reducing cardiovascular outcomes amongst patients with type II DM that go beyond the correction of hyperglycemic perse. Thus an observational imaging study is proposed to identify mechanistic insights of the drug group over cardiovascular events.

Study Overview

• Status: Active, not recruiting
• Conditions: Type2 Diabetes; Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Drug: Dapagliflozin

Detailed Description

Diabetic cardiomyopathy is defined as ventricular dysfunction in diabetic patients in the absence of coronary artery disease and hypertension. It is considered as a cardiac muscle disorder due to the metabolic consequences of DM characterized by left ventricular hypertrophy, left ventricular diastolic dysfunction (in the early stage), and/or systolic dysfunction. To date, there is no specific treatment proven effective for the condition due to the incomplete understanding of the pathogenesis.

Recent studies however prove the efficacy of SGLT-2 inhibitors on reducing the primary composite end point of cardiovascular outcomes including hospitalization for heart failure, cardiovascular death, and all-cause death amongst patients with type II DM. Such clinical benefit is apparently mainly stemmed from the reduction in heart failure related mortality and sudden cardiac death rather than the macro-vascular events such as myocardial infarct and stroke, suggesting addition benefits going beyond the correction of hyperglycemia perse. These studies thus raise the possibility that the drug may have direct effects on the myocardium that conferring the clinical benefit not related the modification of traditional risk factors such as glycemic control, lipid, blood pressure, and obesity.

A single-arm, observational cardiac magnetic resonance imaging study is proposed in type II diabetic patients before and 2 months after initiation of dapagliflozin. The aim is to identify mechanistic insights leading to the unexpected clinical benefit of SGLT inhibition.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• type 2 diabetes
• 40-90 years old
• HbA1c >= 6.5%
• history of heart failure with reduced ejection fraction
• indications for SGLT inhibition on clinical ground

Exclusion Criteria:

• angina pectoris or chest discomfort
• prior coronary artery bypass grafts
• coronary artery stenting within 6 months of study enrolment
• pervious myocardial infarct
• any contraindication for stress CMR testing
• renal impairment with eGFR <45ml/min/1.73m2
• limited life expectancy <5 years, for example due to pulmonary disease, cancer or
• significant hepatic failure
• contraindication to dapagliflozin or other SGLT2 inhibitors
• unable to take dapagliflozin
• patients currently on and SGLT2 inhibitor
• planned need for concomitant cardiac surgery or coronary intervention
• refusal or inability to sign an informed consent
• potential for on-compliance towards the requirements in the trial protocol (especially the medical treatment) or follow-up visits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin, one of the SGLT-2 inhibitors, will be prescribed to DM patients on clinical ground	Drug: Dapagliflozin; Dapagliflozin, one of the SGLT-2 inhibitors, will be prescribed to DM patients on clinical ground.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in myocardial perfusion reserve index	Change in myocardial perfusion reserve index calculated from cardiac MRI	8-12 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: David Chung-Wah SIU, Prof, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2020
• Primary Completion (Actual): March 4, 2021
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 16, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Cardiomyopathies; Diabetic Cardiomyopathies; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: Version no.3

Drug and device information, study documents

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