Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes

Clarke, Geoffrey D.; Solis‐Herrera, Carolina; Molina‐Wilkins, Marjorie; Martínez, Sandra Serrano; Merovci, Aurora; Cersósimo, Eugênio; Chilton, Robert; Iozzo, Patricia; Gastaldelli, Amalia; DeFronzo, Ralph A.; DeFronzo, Ralph A.

doi:10.2337/dc17-0078

Cited by 52 publications

(58 citation statements)

References 42 publications

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“…Whereas pioglitazone is associated with reduced cardiovascular risk, because undiagnosed diastolic dysfunction is more common in patients with NAFLD or T2DM, fluid retention that occurs during pioglitazone therapy may induce congestive cardiac failure and so is contraindicated in these patients. In patients without clinically evident cardiovascular disease, a small recent study found that pioglitazone was associated with improved left ventricular systolic and diastolic function …”

Section: Modulation Of Ir In Nafldmentioning

confidence: 99%

“…In patients without clinically evident cardiovascular disease, a small recent study found that pioglitazone was associated with improved left ventricular systolic and diastolic function. (30) Pioglitazone is associated with an increased risk of bone fractures. (31) A recent meta-analysis has reported that out of 26 studies, only five showed an association between bladder cancer and pioglitazone, (32) with no significant association found after exclusion of studies deemed to be of low quality.…”

Section: Peroxisome Proliferator-activated Receptor Gamma Agonistsmentioning

confidence: 99%

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Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

et al. 2019

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Nonalcoholic fatty liver disease (NAFLD) has an estimated prevalence of 25% in the general population, and cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is predicted to become the leading cause of liver transplantation, yet there is a lack of effective licensed treatments for these conditions. There is a close relationship between insulin resistance (IR) and NAFLD, with prevalence of NAFLD being 5‐fold higher in patients with diabetes compared to those without. IR is implicated both in pathogenesis of NAFLD and in disease progression from steatosis to NASH. Thus, modulation of IR represents a potential strategy for NAFLD treatment. This review highlights key proposed mechanisms linking IR and NAFLD, such as changes in rates of adipose tissue lipolysis and de novo lipogenesis, impaired mitochondrial fatty acid β‐oxidation (FAO), changes in fat distribution, alterations in the gut microbiome, and alterations in levels of adipokines and cytokines. Furthermore, this review will discuss the main pharmacological strategies used to treat IR in patients with NAFLD and their efficacy based on recently published experimental and clinical data. These include biguanides, glucagon‐like peptide 1 receptor (GLP‐1) agonists, dipeptidyl peptidase 4 (DPP‐4) inhibitors, peroxisome proliferator‐activated receptor (PPAR‐γ/α/δ) agonists, sodium glucose cotransporter 2 (SGLT2) inhibitors, and farnesoid X receptor (FXR) agonists, with further novel treatments on the horizon. Ideally, treatment would improve IR, reduce cardiovascular risk, and produce demonstrable improvements in NASH histology—this is likely to be achieved with a combinatorial approach.

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Section: Modulation Of Ir In Nafldmentioning

confidence: 99%

Section: Peroxisome Proliferator-activated Receptor Gamma Agonistsmentioning

confidence: 99%

Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

et al. 2019

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“…Thus, although fluid retention can occur in 5% to 10% of glitazone‐treated T2DM patients, less than 1% will develop HF. Moreover, a recent small clinical study using sophisticated measurement of heart function has suggested that pioglitazone can improve myocardial insulin sensitivity, LV diastolic function and systolic function in T2D . Improved myocardial insulin sensitivity and diastolic function are strongly correlated …”

Section: Safety Considerations: Balance Between Risk and Benefitmentioning

confidence: 99%

“…Moreover, a recent small clinical study using sophisticated measurement of heart function has suggested that pioglitazone can improve myocardial insulin sensitivity, LV diastolic function and systolic function in T2D. 96 Improved myocardial insulin sensitivity and diastolic function are strongly correlated. 96 Weight gain is the most common adverse effect associated with the use of glitazones because of fluid retention and increased adiposity.…”

Section: Safety Considerations: Balance Between Risk and Benefitmentioning

confidence: 99%

“…96 Improved myocardial insulin sensitivity and diastolic function are strongly correlated. 96 Weight gain is the most common adverse effect associated with the use of glitazones because of fluid retention and increased adiposity. The latter, however, is associated with a relative redistribution of adipose tissue from visceral to subcutaneous stores.…”

Section: Safety Considerations: Balance Between Risk and Benefitmentioning

confidence: 99%

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Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

Prato

Chilton

2017

Diabetes Obesity Metabolism

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T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose‐lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control. During the past 10 years, the effect of specific glucose‐lowering agents on cardiovascular risk has been explored with dedicated trials. Overall, the cardiovascular safety of the new glucose‐lowering agents has been proven with some of the trials summarized in this review, showing significant reduction of cardiovascular risk. Against this background, pioglitazone, in addition to exerting a sustained glucose‐lowering effect, also has ancillary metabolic actions of potential interest in addressing the cardiovascular risk of T2DM, such as preservation of beta‐cell mass and function. As such, it seems a logical agent to combine with other oral anti‐hyperglycaemic agents, including dipeptidyl peptidase‐4 inhibitors (DPP4i). DPP4i, which may also have a potential to preserve beta‐cell function, is available as a fixed‐dose combination with pioglitazone, and could, potentially, attenuate some of the side effects of pioglitazone, particularly if a lower dose of the thiazolidinedione is used. This review critically discusses the potential for early combination of pioglitazone and DPP4i.

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Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

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Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes

Cited by 52 publications

References 42 publications

Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease

Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

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