Polypill for Cardiomyopathy Prevention in Type 2 Diabetes

(PolyPreventHF Trial)

Overseen by Ambarish Pandey, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Congestive heart failure, Hyperkalemia, Pregnancy, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study will investigate the utility of a polypill-based strategy for patients with type 2 diabetes mellitus and high risk of heart failure (HF), as assessed via the WATCH-DM risk score. Polypill therapy will consist of empagliflozin 12.5 mg, losartan 50 or 100 mg, and finerenone 10 mg daily. The study duration is 6 months, and participants will be randomized to either polypill therapy or usual care. The primary outcome is change in peak VO2 and adherence to usual care. The investigators hypothesize that the use of a polypill is feasible and improves medication adherence and peak VO2 as compared to those receiving usual care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, since the study involves a polypill therapy, it's possible that adjustments to your current medications might be needed. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug Polypill for preventing cardiomyopathy in patients with type 2 diabetes?

Research shows that dapagliflozin, a component often found in heart failure treatments, can reduce the risk of death and hospital visits in patients with heart failure and reduced ejection fraction, which is a condition where the heart doesn't pump blood as well as it should. This suggests that similar treatments, like the Polypill, might also help prevent heart problems in people with type 2 diabetes. ^{1 2 3 4 5}

Is the Polypill safe for humans?

The safety of the Polypill, which may include components like dapagliflozin, has been evaluated in patients with heart failure and reduced ejection fraction (HFrEF). Dapagliflozin, a component of some Polypills, has been studied for its safety in these patients, even those with kidney issues, suggesting it is generally safe for human use in this context. ^{1 3 6 7 8}

How is the Polypill drug different from other treatments for preventing heart failure in type 2 diabetes?

The Polypill is unique because it combines multiple medications into a single pill, potentially simplifying treatment and improving adherence for patients with type 2 diabetes at risk of heart failure. This approach may address multiple risk factors simultaneously, unlike traditional treatments that often target individual aspects of the condition separately. ^{1 6 9 10 11}

Research Team

Ambarish Pandey, MD

Principal Investigator

UT Southwestern

Eligibility Criteria

This trial is for people with type 2 diabetes who are at high risk of heart failure. They should have a certain level of kidney function and protein in their urine, but not be on dialysis or have severe kidney disease. Pregnant individuals, those unable to exercise for tests, or with very high potassium levels can't join.

Inclusion Criteria

I have Type 2 diabetes, moderate kidney issues, and a high risk of heart failure.

Exclusion Criteria

I have been diagnosed with congestive heart failure.

I am allergic or react badly to one of the ingredients in the polypill.

Your blood has too much potassium, above the level of 5.0.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either polypill therapy or usual care for 6 months

6 months

Visits at baseline, 1 month, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Polypill (Other)

Trial Overview The study is testing a polypill combining three medications (empagliflozin, losartan, finerenone) against usual care over three months. It aims to see if the pill helps patients stick to their treatment better and improves oxygen use during peak exercise.

Participant Groups

Group I: Polypill Experimental Treatment 1 Intervention

Participants will take a polypill containing finerenone 10 mg, empagliflozin 12.5 mg, and losartan (50 mg or 100 mg) daily.

Group II: Usual Care Active Control 1 Intervention

Participants will continue to take normal medications for diabetes and high blood pressure.

Polypill is already approved in India for the following indications:

Approved in India as HFrEF Polypill for:

• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

Heart failure is common in patients with type 2 diabetes and significantly worsens their prognosis, leading to higher rates of hospitalization and mortality.

The article reviews how different antidiabetic medications can impact the incidence and outcomes of heart failure in these patients, highlighting the importance of medication choice in managing both diabetes and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure: an underestimated therapeutic target in diabetes. Marx, N.[2020]

In the DAPA-HF trial, dapagliflozin significantly reduced the risk of worsening heart failure episodes and cardiovascular death, with a 36% lower incidence in patients taking dapagliflozin compared to placebo over a median follow-up of 18.2 months.

Outpatient worsening of heart failure was common and associated with a higher risk of death, but dapagliflozin effectively lowered these events, demonstrating its efficacy in managing heart failure alongside standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. Docherty, KF., Jhund, PS., Anand, I., et al.[2021]

In the DAPA-HF trial involving 4742 patients with heart failure and reduced ejection fraction (HFrEF), dapagliflozin significantly reduced the risk of cardiovascular death or worsening heart failure, regardless of baseline kidney function, indicating its efficacy across different eGFR levels.

Dapagliflozin also slowed the decline in kidney function over time, with a significantly less rate of eGFR decline compared to placebo, demonstrating its potential renal protective effects even in patients without diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. Jhund, PS., Solomon, SD., Docherty, KF., et al.[2021]

In the DAPA-HF trial involving 4744 patients with heart failure and reduced ejection fraction, dapagliflozin significantly reduced the risk of worsening heart failure and cardiovascular death in both ischaemic and non-ischaemic patients, demonstrating its efficacy across different aetiologies.

Dapagliflozin was found to be safe and well-tolerated, with similar rates of serious adverse events and treatment discontinuation compared to placebo, indicating it can be a reliable treatment option for heart failure patients regardless of the underlying cause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial. Butt, JH., Nicolau, JC., Verma, S., et al.[2021]

Diabetes and heart failure (HF) often co-occur, complicating treatment and leading to worse outcomes, highlighting the need for integrated management strategies.

Emerging evidence suggests that diabetes medications can not only help manage diabetes but also reduce heart failure events, even in patients without diabetes, indicating their potential dual benefit in treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Management in Patients with Heart Failure. Shen, J., Greenberg, BH.[2021]

Heart failure (HF) is a significant concern for individuals with diabetes, often linked to conditions like ischaemia and hypertension, but diabetic cardiomyopathy is increasingly recognized as a direct cause of HF.

New glucose-lowering medications are now routinely evaluated for their cardiovascular effects, providing valuable insights into their safety and risks for patients with existing heart failure, which is crucial for developing effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical aspects of heart failure in individuals with diabetes. Bowes, CD., Lien, LF., Butler, J.[2020]

The 2021 European Society of Cardiology guidelines emphasize the importance of early treatment with all four key drug classes for heart failure with reduced ejection fraction (HFrEF), which include ACE inhibitors, ARNI, beta-blockers, MRAs, and SGLT2 inhibitors.

This article serves as a practical guide for physicians to ensure safe and effective management of HFrEF, highlighting the need for comprehensive treatment strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. Soltani, S., Böhm, M., Frey, N., et al.[2022]

Beta-blockers, antialdosterone agents, and combined ARB/neprilysin inhibitors are effective in preventing sudden cardiac death (SCD) and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), based on a review of 41 systematic reviews.

Angiotensin-converting enzyme inhibitors (ACE-i) significantly reduce all-cause mortality but do not prevent SCD, indicating that alternative strategies may be needed for patients at high risk of SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews. Al-Gobari, M., Al-Aqeel, S., Gueyffier, F., et al.[2021]

Sodium glucose transporter-2 inhibitors (SGLT-2i) significantly reduce heart failure events and hospitalizations in patients with type 2 diabetes, as shown in large-scale randomized controlled trials like EMPA-REG OUTCOME and CANVAS.

In contrast to other diabetes medications such as DPP-IV inhibitors and thiazolidinediones, which have shown neutral or negative effects on heart failure, SGLT-2i therapy is effective in preventing heart failure in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications. Bassi, N., Fonarow, GC.[2019]

People with type 2 diabetes have a higher risk of heart failure (HF) and worse outcomes compared to non-diabetics, primarily due to factors like ischemic heart disease and diabetic cardiomyopathy.

While treatments like angiotensin-converting enzyme inhibitors and β-blockers can improve heart function in heart failure with reduced ejection fraction (HFrEF), managing underlying risk factors is crucial for heart failure with preserved ejection fraction (HFpEF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Bell, DSH., Goncalves, E.[2020]

The patient with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF) showed significant improvement in diastolic function and exercise capacity after three weeks of low-carbohydrate nutrition and moderate exercise, highlighting the potential efficacy of metabolic interventions in managing HFpEF.

This case suggests that HFpEF related to insulin resistance is often overlooked in obese patients, and that traditional low-fat dietary recommendations may worsen their condition; instead, a low-carbohydrate diet can effectively reverse insulin resistance and improve cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diastolic heart failure treated by diet]. Heilmeyer, P., von Bibra, H.[2016]

References

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

Heart failure: an underestimated therapeutic target in diabetes. [2020]

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

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. [2021]

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

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. [2021]

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

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial. [2021]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Diabetes Management in Patients with Heart Failure. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Clinical aspects of heart failure in individuals with diabetes. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews. [2021]

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

Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications. [2019]

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

Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

[Diastolic heart failure treated by diet]. [2016]