Empagliflozin for Heart Failure Risk

Overseen By Julie Dicken, RN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must not be taking: SGLT2 inhibitors, GLP1 agonists

Disqualifiers: Diabetes, Heart failure, Pregnancy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

80 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain diabetes medications like SGLT2 inhibitors, GLP1 agonists, or DPP4 inhibitors. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug empagliflozin for heart failure?

Empagliflozin, also known as Jardiance, has been shown to reduce the risk of hospitalization and death in people with heart failure, even if they don't have diabetes. Studies have found that it improves quality of life and is generally well tolerated, making it a valuable option for treating heart failure. ^{1 2 3 4 5}

Is empagliflozin (Jardiance) safe for humans?

Empagliflozin (Jardiance) is generally well tolerated in humans, with a safety profile consistent with its use in treating type 2 diabetes and heart failure. Common side effects include genital infections, especially in women, and a slight increase in mild urinary tract infections. There is a low risk of low blood pressure and dehydration, which should be monitored in vulnerable patients. ^{2 3 4 6 7}

How is the drug empagliflozin unique for treating heart failure?

Empagliflozin is unique because it is a diabetes drug that has been approved to reduce the risk of cardiovascular death and hospitalization in adults with heart failure, even if they do not have diabetes. It works by helping the heart pump blood more effectively and is beneficial across a wide range of heart failure conditions, regardless of other heart failure treatments being used. ^{2 3 4 5 8}

What is the purpose of this trial?

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.

Research Team

Jeremy Van't Hof, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults over 60 with high blood pressure and a BMI of at least 30kg/m2, who may be at risk for heart failure. They must have had an echocardiogram within the last 60 days. It's not specified who can't join, but typically those with conditions that could interfere with the study or their safety would be excluded.

Inclusion Criteria

I have been diagnosed with high blood pressure.

Body mass index ≥30kg/m2

Participants with an echocardiogram within 60 days of the baseline visit

Exclusion Criteria

I have had infections in my urinary or genital area before.

I haven't had, nor am I scheduled for, major surgery around the time of my first visit.

Non-English speaking individuals

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 10mg empagliflozin or placebo daily to assess the effect on left atrial function

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin

Trial Overview The trial is testing empagliflozin, a drug initially used for type 2 diabetes, to see if it improves left atrial function in patients at risk of developing heart failure. Participants will either receive empagliflozin or a placebo without knowing which one they're taking (double-blinded).

Participant Groups

Group I: Experimental group Experimental Treatment 1 Intervention

Group II: Placebo group Placebo Group 1 Intervention

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Empagliflozin has been shown to improve cardiorenal outcomes and reduce hospitalization risk for heart failure in patients with diabetes, as demonstrated in the EMPA-REG OUTCOME study.

Clinical studies (EMPEROR-Preserved, EMPEROR-Reduced, EMPULSE) indicate that empagliflozin provides significant benefits over traditional heart failure therapies, including reduced mortality and hospitalizations, and improved quality of life for patients with various heart failure phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLINICAL EFFECTIVENESS OF EMPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE. Rоsul, ММ., Bletskan, ММ., Ivano, NV., et al.[2023]

Empagliflozin, originally developed for type 2 diabetes, has been shown to significantly reduce the risk of cardiovascular death and hospitalization for heart failure in patients with symptomatic chronic heart failure, regardless of their left ventricular ejection fraction, based on pivotal phase III trials.

The treatment not only improved cardiovascular outcomes but also enhanced health-related quality of life and was well tolerated, with a safety profile similar to that observed in diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: A Review in Symptomatic Chronic Heart Failure. Frampton, JE.[2022]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Empagliflozin (EMPA) significantly reduced the induction of ventricular fibrillation (VF) in an ex-vivo model of ischemia-reperfusion, with only 16.7% of EMPA-treated hearts experiencing VF compared to 60% in control hearts.

EMPA improved cardiac contractility, as shown by a higher left ventricular developed pressure (LVDP) and enhanced calcium cycling, indicating its potential to protect heart function during ischemic events through mechanisms that do not involve sodium-glucose co-transporter-2 (SGLT2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. Azam, MA., Chakraborty, P., Si, D., et al.[2021]

In the EMPEROR-Preserved study involving nearly 6000 participants, empagliflozin significantly reduced the risk of hospitalization for heart failure complications by about 30% after an average treatment duration of 26 months.

While side effects were generally similar between empagliflozin and placebo groups, there was a higher incidence of genital infections in those taking empagliflozin (2.2% vs. 0.7%), indicating a need for monitoring but overall suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin was beneficial in people with heart failure with preserved ejection fraction: plain language summary of the EMPEROR-Preserved study. Zannad, F., Macari, S.[2023]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

References

1. Poland pubmed.ncbi.nlm.nih.gov

CLINICAL EFFECTIVENESS OF EMPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Empagliflozin: A Review in Symptomatic Chronic Heart Failure. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin was beneficial in people with heart failure with preserved ejection fraction: plain language summary of the EMPEROR-Preserved study. [2023]

7. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]