SGLT2 Inhibitors for Heart Failure

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Carolina Solis-Herrera, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: SGLT2 inhibitors, GLP-1 RAs

Disqualifiers: High blood pressure, Low oxygen, others

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses empagliflozin to help people with Type 2 Diabetes and Heart Failure. The medication increases blood ketone levels, which may improve muscle and heart function, exercise capacity, and overall well-being. Empagliflozin has been shown to reduce cardiovascular death and hospitalization for heart failure in patients with type 2 diabetes.

Will I have to stop taking my current medications?

The trial requires that you are on a stable dose of your current heart failure medications. However, if you are taking an SGLT2 inhibitor, GLP-1 RA, or pioglitazone, you cannot participate in the trial.

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

Empagliflozin, a drug initially used for type 2 diabetes, has been shown to reduce the risk of death from heart problems and hospitalizations in people with heart failure, regardless of their heart's pumping ability or diabetes status. It also improves quality of life and is generally well tolerated. ^{1 2 3 4 5}

Is empagliflozin (Jardiance) safe for humans?

Empagliflozin (Jardiance) is generally safe for humans, but it can cause some side effects like fluid deficits, mycotic genital infections (fungal infections), and a slight increase in mild urinary tract infections. It has been shown to reduce cardiovascular mortality in people with type 2 diabetes and heart failure, but patients should be monitored for low blood pressure and dehydration, especially if they are more fragile. ^{6 7 8 9 10}

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 inhibiting SGLT2, which helps the heart function better and reduces fluid retention, making it a novel option for heart failure treatment. ^{1 6 7 11 12}

Research Team

Carolina Solis-Herrera, MD

Principal Investigator

University of Texas Health Science Center San Antonio

Eligibility Criteria

This trial is for adults aged 18-80 with Type 2 Diabetes and moderate heart failure (NYHA Class II-III) who have a reduced heart function (EF <50%). They should have a stable weight, controlled blood pressure, and not be on certain diabetes or heart failure medications. People with very high resting heart rates, extreme hypertension, low oxygen levels at rest, or physical disabilities that prevent exercise are excluded.

Inclusion Criteria

My heart failure medication dose has been stable.

I am between 18 and 80 years old.

Your kidney function is good, with a filtration rate of at least 30 ml/min•1.73 m2.

Exclusion Criteria

I am currently taking medication for diabetes that includes SGLT2 inhibitors, GLP-1 receptor agonists, or pioglitazone.

Your blood pressure is too high (systolic BP>180mmHg and/or diastolic BP >100mmHg).

I have a physical disability that makes it unsafe for me to do certain exercises.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin or placebo for 12 weeks to study effects on skeletal muscle and cardiac ketone uptake, among other outcomes

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin 25 MG (SGLT2 Inhibitor)
• Placebo (Drug)

Trial Overview The study is testing the effects of Empagliflozin (a drug for diabetes that also affects fat metabolism) against a placebo in improving muscle energy use, exercise capacity, and patient-reported outcomes in those with both Type 2 Diabetes and heart failure.

Participant Groups

Group I: Empagliflozin Group Experimental Treatment 1 Intervention

Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months

Group II: Placebo group Placebo Group 1 Intervention

Subjects will be randomized to receive the empagliflozin placebo for 3 months

Empagliflozin 25 MG is already approved in Canada for the following indications:

Approved in Canada as Jardiance for:

• Type 2 diabetes
• Established cardiovascular disease

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Dr. Andrew Masica

The University of Texas Health Science Center at San Antonio

Chief Medical Officer

MD from Indiana University School of Medicine

Dr. Taylor Eighmy

The University of Texas Health Science Center at San Antonio

Acting President

PhD in Civil Engineering from the University of New Hampshire

Max and Minnie Tomerlin Voelcker Fund

Collaborator

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Samsher (Sam) Singh Gill

Doris Duke Charitable Foundation

Chief Executive Officer since 2021

Rhodes Scholar

Rochelle Walensky

Doris Duke Charitable Foundation

Chief Medical Officer since 2023

MD, MPH

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

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]

SGLT2 inhibitors significantly reduce the risk of clinical events in heart failure patients, showing benefits regardless of factors like ejection fraction and diabetes status.

This review provides a practical guide for clinicians on how to effectively prescribe SGLT2 inhibitors, emphasizing the importance of patient selection and management to minimize potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians. Monzo, L., Ferrari, I., Cicogna, F., et al.[2023]

In patients with acute heart failure, empagliflozin significantly increased glucose excretion without affecting sodium excretion, indicating that its mechanism of action primarily involves osmotic diuresis through increased glycosuria.

The treatment caused a temporary decline in kidney function (estimated glomerular filtration rate) shortly after administration, but this decline recovered within 30 days, suggesting that while there are initial risks, the long-term effects may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure. Boorsma, EM., Beusekamp, JC., Ter Maaten, JM., et al.[2021]

SGLT-2 inhibitors, originally used for type 2 diabetes, have been shown to significantly reduce mortality and hospitalization rates in heart failure patients, leading to their inclusion as essential treatments in recent American and European guidelines.

While the exact mechanisms of how SGLT-2 inhibitors improve heart failure outcomes are not fully understood, they are believed to involve various metabolic and hemodynamic effects, highlighting their potential as adjunctive therapy in managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses. March, KL., Lukas, JG., Berei, TJ., et al.[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) 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]

Empagliflozin, an SGLT2 inhibitor, is effective in improving blood sugar control in adults with type 2 diabetes, especially when metformin is not suitable.

In addition to managing diabetes, empagliflozin also aims to reduce cardiovascular risks associated with the condition, highlighting its dual role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

Empagliflozin (Jardiance) is a new medication classified as an SGLT2 inhibitor, specifically designed to help manage blood sugar levels in individuals with type-2 diabetes.

This medication not only aids in lowering blood glucose but also has potential benefits for heart health, making it a promising option for patients with diabetes at risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. Ndefo, UA., Anidiobi, NO., Basheer, E., et al.[2020]

In a study of 158 patients aged 80 and older with type 2 diabetes and acute heart failure, continuing empagliflozin treatment led to significantly lower NT-proBNP levels, indicating improved heart function compared to those on a conventional insulin regimen.

Patients on empagliflozin also experienced better diuretic response and increased urine output during hospitalization, while showing no significant differences in safety outcomes, suggesting it is a safe and effective option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure. Pérez-Belmonte, LM., Sanz-Cánovas, J., Millán-Gómez, M., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians. [2023]

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

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure. [2021]

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

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses. [2022]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

7. 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]

8. Belgium pubmed.ncbi.nlm.nih.gov

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

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

SGLT2 inhibitors: new reports. [2019]

10. England pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

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

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. [2020]

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

Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure. [2022]