SGLT2 Inhibitors for Heart Failure

Recruiting at 1 trial location

Overseen By Yuejuan Qin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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 This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called empagliflozin (an SGLT2 inhibitor) to assess its effects on heart and muscle health in people with type 2 diabetes and heart failure. Participants will be randomly assigned to take either the medication or a placebo (a look-alike pill with no active ingredient) for three months. The goal is to determine if empagliflozin can improve muscle energy use, exercise ability, and overall health. Individuals with type 2 diabetes, moderate heart failure, and no prior use of certain diabetes medications are the best fit for this trial. As an Early Phase 1 trial, this study focuses on understanding how empagliflozin works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that empagliflozin is generally safe for people with heart failure. In earlier studies, patients taking empagliflozin had fewer hospital visits for heart failure and a reduced risk of dying from heart-related issues. Most patients tolerated empagliflozin well, with few experiencing serious side effects. Empagliflozin's FDA approval for other uses adds confidence to its safety profile. While every treatment can have side effects, current evidence suggests that empagliflozin is quite safe for heart failure patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart failure, which often include medications like ACE inhibitors or beta-blockers, empagliflozin is unique because it is an SGLT2 inhibitor. This class of drugs primarily targets the kidneys to reduce glucose reabsorption, but it also offers cardiovascular benefits by reducing fluid overload and potentially improving heart function. Researchers are excited about empagliflozin because it provides a dual benefit of managing blood sugar levels in diabetic patients while also offering promising heart failure management, which could lead to better outcomes for patients with heart failure.

What evidence suggests that empagliflozin might be an effective treatment for heart failure?

Research has shown that empagliflozin, which participants in this trial may receive, effectively treats heart failure. In several studies, this medication reduced the risk of hospital visits for heart failure. For patients with heart failure and normal heart pumping ability, empagliflozin lowered the combined risk of dying from heart problems or needing hospital care for heart issues. It also benefited people with diabetes and heart problems by improving heart health and reducing hospital stays. These studies suggest that empagliflozin could be a promising treatment option for heart failure. ^{1 4 6 7 8}

Who Is on the Research Team?

Carolina Solis-Herrera, MD

Principal Investigator

University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

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.

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

Your weight has not changed by more than 4 pounds in the last 3 months.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin 25 MG
• Placebo

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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes
• Symptomatic chronic heart failure
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease
• Cardiovascular risk reduction

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+

Max and Minnie Tomerlin Voelcker Fund

Collaborator

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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, 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]

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]

SGLT2 inhibitors (SGLT2i) showed a trend towards reducing the risk of cardiovascular death or heart failure hospitalization compared to sacubitril/valsartan and vericiguat, indicating their potential effectiveness in heart failure treatment.

SGLT2i demonstrated the greatest reduction in heart failure hospitalization rates compared to standard care and vericiguat, suggesting they may be the most effective therapy among the treatments analyzed.

NCBI (Pubmed)

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. Aimo, A., Pateras, K., Stamatelopoulos, K., et al.[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]

Citations

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HFpEF Efficacy & Data | Jardiance® (empagliflozin) tablets JARDIANCE reduced the number of worsening HF events · In a secondary analysis of the EMPEROR-Preserved trial, JARDIANCE improved time to worsening HF events, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107038

Empagliflozin in Heart Failure with a Preserved Ejection ... Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5253088/

Impact of Empagliflozin in Patients with Diabetes and Heart ... Empagliflozin was shown to improve cardiovascular outcomes in patients with T2DM and established cardiovascular risk where it reduced HF hospitalizations and ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069217

Effect of Empagliflozin on Heart Failure Outcomes After ... Empagliflozin reduced the risk of first and total heart failure (HF) hospitalizations by 23% and 33%, respectively, in patients with left ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2023.03.390

Efficacy of Empagliflozin in Patients With Heart Failure ... Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6416009/

Empagliflozin Reduced Mortality and Hospitalization for Heart ... Despite all patients having atherosclerotic cardiovascular disease, patients in EMPA-REG OUTCOME demonstrated a broad risk spectrum for cardiovascular events.

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.040921

Empagliflozin and Heart Failure | Circulation For the primary outcome, initiation of empagliflozin was associated with a 50% lower risk of HHF compared with sitagliptin (hazard ratio, 0.50 [ ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666273625000919

Safety and efficacy of empagliflozin in heart failure among ... Although VHD history was associated with worse outcomes in HF patients, empagliflozin demonstrated consistent safety, efficacy, and patient-reported outcomes ...