Effect of Empagliflozin on Left Atrial Function in Adults at Risk for Heart Failure

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce CVD events, including incident HF. SGLT2 is a glucose transport protein in the kidneys. Inhibition of this protein results in glucosuria and lower serum blood sugar. The SGLT2i medications were initially approved to treat type 2 diabetes (T2D). In 2015, Zinman et al. published the first large randomized clinical trial (RCT) demonstrating a lower composite CVD outcome in adults with T2D treated with empagliflozin compared to placebo (HR 0.85, 95% CI 0.74-0.99). In the specific case of empagliflozin, the hazard ratio was 0.75 (95% CI 0.65-0.86) for HFrEF 8 and 0.79 (95% CI 0.69-0.90) for HFpEF using a treatment dose of 10mg daily.

The purpose of this placebo-controlled, double-blinded, randomized pilot study is to investigate the effect of empagliflozin on left atrial (LA) function in 80 patients who are at risk for heart failure. Participants will be randomized 1:1 to either intake of a 10mg empagliflozin oral tablet or a matching placebo once daily.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Hypertension
• Intervention / Treatment: Drug: empagliflozin; Drug: Placebo tablet

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Julie Dicken, RN; Email: dicke022@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Julie Dicken; Email: dicke022@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >60 years of age
• Clinical diagnosis of hypertension
• Body mass index ≥30kg/m2
• We will screen for participants with an echocardiogram within 60 days of the baseline visit

Exclusion Criteria:

• Female participants who are pregnant, lactating, or of child bearing potential
• History of type 1 or type 2 diabetes mellitus by medical history or hemoglobin A1c >7.0% at Visit 1
• Clinical diagnosis of HFpEF or HFrEF by participant self-report or documented in the electronic health record
• Any LVEF measure of ≤40% on past echocardiogram
• Moderate or severe valve disease on echocardiogram
• History of genitourinary infection
• eGFR <60 ml/min/1.73 m2 at Visit 1
• Current treatment with SGLT2 inhibitor, GLP1 agonist, or DPP4 inhibitors
• Participants in whom coronary revascularization by either PCI or bypass surgery is being contemplated within 6 months, or who have undergone revascularization in the prior 2 months
• Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the formulations
• Participants currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease, and psychiatric disease
• Any malignancy not considered cured (except basal cell carcinoma of the skin). A participant is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening
• Participants who have participated in studies of an investigational drug or device within 30 days prior to the screening visit
• Inadequate quality echocardiographic images
• Unstable coronary syndromes
• Major surgery (major according to the investigator's assessment) performed within 90 days prior to Visit 1 or scheduled major elective surgery within 90 days after Visit 1.
• Non-English speaking individuals

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Drug: Placebo tablet; intake a placebo oral tablet At visit 1, after randomization, participants will be provided with bottles containing enough study pills for 3 months duration at 1 tablet daily. Participants will start the study drug on the morning following Visit 1. At the 3 month follow up visit, participants will be provided with enough study pills to complete the remaining 6 months of the study.
Experimental: Experimental group	Drug: empagliflozin; intake of a 10mg empagliflozin oral tablet At visit 1, after randomization, participants will be provided with bottles containing enough study pills for 3 months duration at 1 tablet daily. Participants will start the study drug on the morning following Visit 1. At the 3 month follow up visit, participants will be provided with enough study pills to complete the remaining 6 months of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in LA function	LA function will be quantified by assessing LA reservoir, conduit, and contractile strain with 2DE at baseline and 9 months.	9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
change in left ventricular ejection fraction	9 months
change in global longitudinal strain	9 months
change in mass (indexed to body surface area)	9 months
change in E/e' ratio	9 months
change in plasma protein levels: DLK-1 (protein delta homolog 1)	9 months
change in plasma protein levels: GDF15 (growth differentiating factor 15)	9 months
change in plasma protein levels: Spondin-1	9 months
change in plasma protein levels: IGBPF-7	9 months
change in plasma protein levels: THBS-2 (thrombospondin 2)	9 months
change in plasma protein levels: IGFBP-1 (insulin-like binding factor protein 1)	9 months
change in plasma protein levels: FABP-4 (fatty acid-binding protein 4)	9 months
change in plasma protein levels: CCL16 (C-C motif chemokine 16)	9 months
change in cardiovascular disease biomarker C-reactive protein (CRP)	3 months and 9 months
change in cardiovascular disease biomarker Troponin	3 months and 9 months
change in cardiovascular disease biomarker NT-proBNP	3 months and 9 months
changes in blood pressure ration	1, 3 and 9 months

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Jeremy Van't Hof, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2029

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Hypertension; Cardiovascular Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; empagliflozin
• Other Study ID Numbers: CV-2023-32230

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No