Acipimox + Empagliflozin for Heart Failure and Type 2 Diabetes

Recruiting in Palo Alto (17 mi)

Overseen by Ralph A DeFronzo, 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 be taking: SGLT2 inhibitors

Must not be taking: DPP4 inhibitors, Pioglitazone

Disqualifiers: Cancer, Pregnancy, Drug use, others

Trial Summary

What is the purpose of this trial?

The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of guideline-directed medications for heart failure, so you may need to continue your current heart failure medications. However, if you are taking Dipeptidyl Peptidase-4 Inhibitors (DPP4i) or pioglitazone for diabetes, you will need to stop those medications to participate.

What data supports the effectiveness of the drug empagliflozin for heart failure and type 2 diabetes?

Research shows that empagliflozin (Jardiance) helps reduce the risk of hospitalization and death in people with heart failure, and it also lowers blood sugar levels in people with type 2 diabetes. This makes it effective for managing both heart failure and diabetes. ^{1 2 3 4 5}

Is the combination of Acipimox and Empagliflozin safe for humans?

Empagliflozin (Jardiance) is generally safe for humans, but it can cause some side effects like fluid deficits, a risk of euglycemic diabetic ketoacidosis (a serious condition where the body produces high levels of blood acids called ketones), and mycotic genital infections (fungal infections in the genital area). It has been shown to reduce cardiovascular events and delay kidney disease progression in people with type 2 diabetes, but caution is advised in certain situations, such as acute illness or when insulin is reduced or stopped. ^{1 4 5 6 7}

How is the drug Acipimox + Empagliflozin unique for treating heart failure and type 2 diabetes?

The combination of Acipimox and Empagliflozin is unique because Empagliflozin, a drug that helps lower blood sugar by causing the body to excrete glucose through urine, is also effective in reducing the risk of hospitalization and cardiovascular death in heart failure patients, even those without diabetes. This dual benefit makes it a novel option for patients with both heart failure and type 2 diabetes. ^{1 4 5 6 8}

Research Team

Ralph A DeFronzo, MD

Principal Investigator

University of Texas Health Science Center San Antonio

Eligibility Criteria

This trial is for high-risk individuals with type 2 diabetes and heart failure who have a reduced ability of the heart to pump blood (HFrEF). Participants should not be currently using SGLT2 inhibitors or medications affecting ketone levels.

Inclusion Criteria

BMI 23-38 kg/m2

I am between 18 and 80 years old.

Stable body weight (±4 pounds) over the last 3 months

Exclusion Criteria

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

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

Systolic BP>180mmHg and/or diastolic BP >100mmHg

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 the effects on plasma ketone levels and heart function

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin (Other)
• Ketones (Other)

Trial Overview The study is testing if Acipimox, Empagliflozin, or a placebo can improve heart function by increasing ketone levels in the blood. The effects on the left ventricle's pumping ability are measured.

Participant Groups

Group I: Empagliflozin Group Experimental Treatment 2 Interventions

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

Group II: Placebo group Placebo Group 2 Interventions

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

Empagliflozin is already approved in Canada, Japan for the following indications:

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?

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

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

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 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 (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]

Empagliflozin, an SGLT2 inhibitor, is effective in managing blood glucose levels and reducing cardiovascular risks in patients with type 2 diabetes, but it can also lead to euglycemic diabetic ketoacidosis under certain conditions, such as acute illness or reduced carbohydrate intake.

A case study of a 23-year-old female with poorly controlled diabetes on empagliflozin revealed severe euglycemic metabolic acidosis and elevated urine ketones during a COVID-19 infection, highlighting the need for careful monitoring in patients using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Severe Metabolic Acidosis due to Jardiance-Induced Euglycemic Diabetic Ketoacidosis. Dyatlova, N., Omotosho, YB., Sherchan, R., et al.[2021]

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 (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]

In a 52-week phase 4 trial involving Japanese patients with type 2 diabetes, empagliflozin as an add-on to liraglutide was well tolerated, with 59.4% to 66.7% of patients reporting at least one adverse event, indicating a manageable safety profile.

The combination therapy resulted in significant improvements in glycaemic control (reduction in HbA1c), body weight, and blood pressure, demonstrating its efficacy in enhancing diabetes management compared to liraglutide alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Empagliflozin as Add-On Therapy to GLP-1 Receptor Agonist (Liraglutide) in Japanese Patients with Type 2 Diabetes Mellitus: A Randomised, Double-Blind, Parallel-Group Phase 4 Study. Terauchi, Y., Utsunomiya, K., Yasui, A., et al.[2020]

References

1. 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]

2. Poland pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

A Case of Severe Metabolic Acidosis due to Jardiance-Induced Euglycemic Diabetic Ketoacidosis. [2021]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

6. Belgium pubmed.ncbi.nlm.nih.gov

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

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

SGLT2 inhibitors: new reports. [2019]

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

Safety and Efficacy of Empagliflozin as Add-On Therapy to GLP-1 Receptor Agonist (Liraglutide) in Japanese Patients with Type 2 Diabetes Mellitus: A Randomised, Double-Blind, Parallel-Group Phase 4 Study. [2020]