Abstract:
:The ever-growing global burden of congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM) as well as their co-existence necessitate that anti-diabetic pharmacotherapy will modulate the cardiovascular risk inherent to T2DM while complying with the accompanying restrictions imposed by CHF. The thiazolidinedione (TZD) family of peroxisome proliferator-activated receptor γ (PPARγ) agonists initially provided a promising therapeutic option in T2DM owing to anti-diabetic efficacy combined with pleiotropic beneficial cardiovascular effects. However, the utility of TZDs in T2DM has declined in the past decade, largely due to concomitant adverse effects of fluid retention and edema formation attributed to salt-retaining effects of PPARγ activation on the nephron. Presumably, the latter effects are potentially deleterious in the context of pre-existing fluid retention in CHF. However, despite a considerable body of evidence on mechanisms responsible for TZD-induced fluid retention suggesting that this class of drugs is rightfully prohibited from use in CHF patients, there is a paucity of experimental and clinical studies that investigate the effects of TZDs on salt and water homeostasis in the CHF setting. In an attempt to elucidate whether TZDs actually exacerbate the pre-existing fluid retention in CHF, our review summarizes the pathophysiology of fluid retention in CHF. Moreover, we thoroughly review the available data on TZD-induced fluid retention and proposed mechanisms in animals and patients. Finally, we will present recent studies challenging the common notion that TZDs worsen renal salt and water retention in CHF.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Goltsman I,Khoury EE,Winaver J,Abassi Zdoi
10.1016/j.pharmthera.2016.09.007subject
Has Abstractpub_date
2016-12-01 00:00:00pages
75-97eissn
0163-7258issn
1879-016Xpii
S0163-7258(16)30163-2journal_volume
168pub_type
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