Pioglitazone for Heart Failure in Type 2 Diabetes (PIOHF Trial)
Palo Alto (17 mi)Overseen byRalph DeFronzo, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: The University of Texas Health Science Center at San Antonio
Prior Safety Data
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?Our goal of the study is to learn the effects of the diabetes medication named Pioglitazone, in type-2 diabetic obese participants with Heart failure. The main question it aims to answer are:
1. To demonstrate that impaired mitochondrial function leading to reduced ATP generation plays a key pathophysiologic role in the development of heart failure with preserved ejection fraction (HFpEF) in obese type 2 diabetic (T2D) individuals.
2. To demonstrate that pioglitazone, improves diastolic (as well as systolic) function by improving myocardial insulin sensitivity and by reducing both myocardial and epicardial fat content.
What safety data exists for Pioglitazone in heart failure treatment for type 2 diabetes?The provided research does not contain specific safety data for Pioglitazone or its related names (Actos, Actoplus Met, etc.) in the context of heart failure treatment for type 2 diabetes. The studies focus on other pharmacological agents and their effects on heart failure, such as SGLT2 inhibitors and spironolactone, but do not mention Pioglitazone. Therefore, additional sources would be needed to find safety data specific to Pioglitazone in this context.1791012
Do I need to stop my current medications for this trial?The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking GLP-1 RA, thiazolidinedione, or SGLT2i. You can continue if you are on diet/exercise, metformin, sulfonylurea, metformin/SU, DPP4i, or insulin.
Is the drug Pioglitazone a promising treatment for heart failure in people with type 2 diabetes?Pioglitazone shows potential as it can improve heart function and reduce heart-related problems in people with type 2 diabetes. It helps manage diabetes and may improve heart health by affecting heart function positively.456811
What data supports the idea that Pioglitazone for Heart Failure in Type 2 Diabetes is an effective drug?The available research shows that Pioglitazone can improve heart function in patients with type 2 diabetes. One study compared Pioglitazone to another drug, glyburide, and looked at heart function in patients with heart failure. Another study found that Pioglitazone can reduce heart-related problems in people with type 2 diabetes. Additionally, Pioglitazone has been shown to improve blood sugar control and reduce some heart disease risks, making it an effective option for managing type 2 diabetes.234511
Eligibility Criteria
This trial is for obese individuals aged 30-70 with type-2 diabetes and heart failure (NYHA class II-III) who have an ejection fraction over 50%. Participants should be on certain diabetes medications but not on GLP-1 RA, thiazolidinedione, or SGLT2i. They must have stable heart medication use and no history of severe heart conditions unrelated to their diabetes.Inclusion Criteria
I have type 2 diabetes and am treated with specific medications or diet/exercise.
My kidney function is good.
I am between 30 and 70 years old.
I have moderate heart failure.
My heart pumps well (EF > 50%).
Exclusion Criteria
I have a history of osteoporosis or diabetic eye disease.
I have been treated with a medication for diabetes that belongs to the SGLT2 inhibitors class.
I do not have heart failure or severe heart conditions.
My heart failure medication has significantly changed in the last month.
I am currently taking GLP-1 receptor agonists or thiazolidinediones.
I have symptoms of heart disease.
Treatment Details
The study tests Pioglitazone's effect on heart function in diabetic patients with heart failure. It aims to see if the drug can improve energy production in the heart by reducing fat around it and increasing insulin sensitivity. Half will receive Pioglitazone; the other half a placebo.
2Treatment groups
Active Control
Placebo Group
Group I: Pioglitazone Administration GroupActive Control1 Intervention
Pioglitazone 15mg/day titrated to 30 mg/day at week 2 and to 45 mg/day at week 4
Group II: Placebo/Control GroupPlacebo Group1 Intervention
Placebo
Pioglitazone is already approved in United States for the following indications:
🇺🇸 Approved in United States as Actos for:
- Type 2 diabetes mellitus
Find a clinic near you
Research locations nearbySelect from list below to view details:
Texas Diabetes Institute/UHSan Antonio, TX
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Who is running the clinical trial?
The University of Texas Health Science Center at San AntonioLead Sponsor
References
Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. [2018]This individually randomized, open-label, parallel-group pilot study was designed to test the hypothesis that the ability of loop diuretics to interfere with cardiac fibrosis in chronic heart failure (CHF) may be different between compounds.
Spotlight on pioglitazone in type 2 diabetes mellitus. [2019]Pioglitazone (Actos(trade mark)) is an antihyperglycemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and edema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin, or a sulfonylurea, induced both long- and short-term improvements in glycemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.
Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes. [2022]To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention.
Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction. [2022]Thiazolidinediones are associated with fluid retention, often interpreted as worsening cardiac function, limiting their use in patients with heart failure (HF). We compared the effects of pioglitazone and glyburide on cardiac function in patients with type 2 diabetes, systolic dysfunction, and New York Heart Association (NYHA) functional Class II/III HF.
Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. [2021]To compare the risk of acute myocardial infarction, heart failure, and death in patients with type 2 diabetes treated with rosiglitazone and pioglitazone.
Comparison of pioglitazone vs glyburide in early heart failure: insights from a randomized controlled study of patients with type 2 diabetes and mild cardiac disease. [2018]Pioglitazone may cause fluid retention, a well-known side effect of thiazolidinediones, and may exacerbate heart failure. Patients with type 2 diabetes and mild cardiac disease (New York Heart Association functional class I) received pioglitazone (n=151) or glyburide (n=149) for 1 year. The primary endpoint was change in distance covered in the 6-minute walk test. Main secondary endpoints included comparison of cardiovascular mortality and morbidity, analysis of changes from baseline in cardiac structure and function by echocardiogram, and lipid panel. There was no significant treatment difference in the mean change from baseline in the 6-minute walk test (-11.7 m [95% confidence interval, -29.79 to 6.42]). Cardiovascular mortality and morbidity were not significantly different between the treatment groups. Echocardiographic data suggested no significant deterioration in cardiac function with pioglitazone, although more heart failure (10 vs 7 patients), edema (21.2% vs 12.8%), and weight gain (2.56+/-4.62 kg vs 0.86+/-3.85 kg) were observed than with glyburide.
Use, tolerability and compliance of spironolactone in the treatment of heart failure. [2021]Risk of morbidity and mortality in patients with severe heart failure (HF) is reduced by blockade of aldosterone receptors with spironolactone. However, benefits of spironolactone are potentially limited by treatment compliance and adverse events profile. The aim of this study was to estimate use of spironolactone by patients with HF, incidence of key adverse events, and patient compliance.
Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction. [2020]Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.
The dawn of the four-drug era? SGLT2 inhibition in heart failure with reduced ejection fraction. [2021]Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).
Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines. [2022]Heart failure (HF) is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and associated with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. It is classified according to left ventricular ejection fraction (LVEF): HF with reduced EF (HFrEF) with an LVEF of ≤40%, HF with mildly reduced EF (HFmrEF) with an LVEF of 41 to 49%, HF with preserved EF (HFpEF) with an LVEF of ≥50%, and HF with improved EF (HFimpEF) with a baseline LVEF of ≤40%, a ≥ 10% increase from baseline LVEF, and a second measurement of LVEF of >40%. Despite the remarkable progress in the management of HF over the past decades, its prognosis is still poor with higher rates of mortality and hospitalization due to worsening HF. Therefore, the development of novel strategies including pharmacologic therapy is needed to further improve its prognosis. Recent large-scale clinical trials have demonstrated the efficacy of newer pharmacological agents including angiotensin II receptor/neprilysin inhibitor (ARNI), sacubitril/valsartan, type 2 sodium-glucose cotransporter (SGLT2) inhibitors, dapagliflozin, empagliflozin and sotagliflozin, and soluble guanylyl cyclase (sGC) stimulator, vericiguat, and cardiac myosin activator, omecamtiv mecarbil. This review focuses the recent advances in the pharmacological agents for treatment of chronic heart failure, including their mechanisms of action, the evidence based on the clinical trials, and the guideline recommendations for their use.
Change in left ventricular diastolic function after pioglitazone treatment in patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis. [2023]Pioglitazone is currently used as an anti-diabetic agent and can reduce cardiovascular events in in patients with type 2 diabetes mellitus (T2DM). Left ventricular diastolic dysfunction has been recognized as an early manifestation of myocardial dysfunction in T2DM patients. This systematic review and meta-analysis aimed to investigate changes in the left ventricular diastolic function after the treatment of pioglitazone.
The Heart Failure Knights. [2023]The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and proposed four drug classes, the so-called 4 "pillars" (angiotensin-converting enzyme inhibitors; angiotensin receptor-neprilysin inhibitors; beta-blockers; mineralocorticoid receptor antagonists and sodium-glucose co-transporter 2 inhibitors) to be initiated and titrated in all patients with reduced ejection fraction HF (HFrEF). In addition, new molecules have been considered, derived from recently reported advances from trials in HFrEF. In this review, Authors examine in particular these new molecules, as further "knights" for HF. In particular, vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. The selective cardiac myosin activator omecamtiv mecarbil and the cardiac myosin inhibitors aficamten and mavacamten are under investigation. Cardiac myosin stimulator, omecamtiv mecarbil, has shown efficacy in HFrEF, lowering HF related events or cardiovascular death, while the 2 inhibitors, mavacamten and aficamten have been shown to reduce hypercontractility and left ventricular outflow obstruction improving functional capacity in randomized trials targeting hypertrophic cardiomyopathy. These agents are the prototypes of active pipelines promising to deliver an array of molecules against HF in the near future.