SGLT2 inhibitors and cirrhosis: A unique perspective on the comanagement of diabetes mellitus and ascites

Saffo, Saad; Taddei, Tamar H.

doi:10.1002/cld.714

Cited by 38 publications

(35 citation statements)

References 13 publications

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“…NASH is a rising cause of cirrhosis worldwide and is frequently associated with T2D. Although these drugs have been shown to be safe in patients with NASH cirrhosis, (2,3) their usefulness in the management of cirrhotic ascites and edema has not been examined. We have described three cases of patients with cirrhosis, T2D mellitus, and fluid retention with normal baseline creatinine, in whom the use of SGLT2-I had a beneficial effect on fluid retention, with improvement in serum sodium, without development of AKI or encephalopathy, and without evidence of hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…SGLT2-I appear to be safe and well-tolerated in patients with cirrhosis, (2) and because, besides promoting urinary glucose excretion, they also promote sodium excretion, they could have an additional benefit in those with ascites. (3) We describe the course of fluid retention in 3 patients with NASH cirrhosis and T2D who received SGLT2-I.…”

Section: Sodium-glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema In Patients With Cirrhosis And Diabetesmentioning

confidence: 99%

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Sodium‐Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes

Montalvo-Gordon¹,

Chi-Cervera²,

García–Tsao

2020

Hepatology

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Section: Discussionmentioning

confidence: 99%

Section: Sodium-glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema In Patients With Cirrhosis And Diabetesmentioning

confidence: 99%

Sodium‐Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes

Montalvo-Gordon¹,

Chi-Cervera²,

García–Tsao

2020

Hepatology

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“…SGLT2 inhibitors have been shown to have significant diuretic effects and, interestingly, without altering the intravascular volume, they can induce interstitial fluid clearance[ 74 ]. In addition to inducing glycosuria and natriuresis, these agents have beneficial effects on neurohormonal regulation and hepatorenal fibrosis[ 75 ]. Given that DM is also a risk factor for lymphatic dysfunction, SGLT2 inhibitors may be potentially helpful in diabetic patients with cirrhosis, with lymphatic dysfunction.…”

Section: Therapeutic Perspectivementioning

confidence: 99%

Lymphatic dysfunction in advanced cirrhosis: Contextual perspective and clinical implications

Kumar¹,

Anand²,

Priyadarshi³

2021

WJH

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The lymphatic system plays a very important role in body fluid homeostasis, adaptive immunity, and the transportation of lipid and waste products. In patients with liver cirrhosis, capillary filtration markedly increases, primarily due to a rise in hydrostatic pressure, leading to enhanced production of lymph. Initially, lymphatic vasculature expansion helps to prevent fluid from accumulating by returning it back to the systemic circulation. However, the lymphatic functions become compromised with the progression of cirrhosis and, consequently, the lymphatic compensatory mechanism gets overwhelmed, contributing to the development and eventual worsening of ascites and edema. Neurohormonal changes, low-grade chronic inflammation, and compounding effects of predisposing factors such as old age, obesity, and metabolic syndrome appear to play a significant role in the lymphatic dysfunction of cirrhosis. Sustained portal hypertension can contribute to the development of intestinal lymphangiectasia, which may rupture into the intestinal lumen, resulting in the loss of protein, chylomicrons, and lymphocyte, with many clinical consequences. Rarely, due to high pressure, the rupture of the subserosal lymphatics into the abdomen results in the formation of chylous ascites. Despite being highly significant, lymphatic dysfunctions in cirrhosis have largely been ignored; its mechanistic pathogenesis and clinical implications have not been studied in depth. No recommendation exists for the diagnostic evaluation and therapeutic strategies, with respect to lymphatic dysfunction in patients with cirrhosis. This article discusses the perspectives and clinical implications, and provides insights into the management strategies for lymphatic dysfunction in patients with cirrhosis.

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“…We also limit cases of the poor hepatic reserve to cases of Child A or so because dehydration may lead to deterioration of encephalopathy. On the other hand, since it has a sodium excretion function, it is expected to improve ascites in patients with ascites [19].…”

Section: Fig-1: Effect Of Sglt2 Inhibitors On Hepatic Fat Content Evamentioning

confidence: 99%

Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease

Sumida

Yoneda

Tokushige

et al. 2020

Diab Res Open Access

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A fourth of the adult population is now suffering from nonalcoholic fatty liver disease (NAFLD) worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to liver-related mortality. NAFLD/NASH is closely associated with type 2 diabetes. Although pioglitazone is now recommended as the 1st line therapy for NASH with type 2 diabetes, pioglitazone has several safety concerns such as body weight gain, heart failure, fluid retention, and bone fracture in women. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have a variety of functions such as glycemic control, bodyweight reduction, and decreased body pressure. Accumulating evidence has shown that this agent has also cardioprotective and renoprotective effects in patients with or without type 2 diabetes. Recent studies that SGLT2 inhibitor can also reduce in transaminase activities or hepatic fat content in NAFLD. NAFLD patients with type 2 diabetes can be indicated for SGLT2 inhibitor, because they are obese, have insulin resistance, and at high risk of cardiovascular events. The phase 3 study of dapagliflozin for NAFLD (DEAN study) is now ongoing. It remains unknown whether this agent can ameliorate hepatic fibrosis in NASH, leading to improved over-all or liver-related survival. Since the leading cause of NAFLD mortality is cardiovascular events, SGLT2 inhibitors will become the 1st line treatment for NAFLD/NASH.

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SGLT2 inhibitors and cirrhosis: A unique perspective on the comanagement of diabetes mellitus and ascites

Abstract: http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/11-6-reading-taddei a video presentation of this article https://www.wileyhealthlearning.com/Activity/6515816/disclaimerspopup.aspx questions and earn CME

Cited by 38 publications

References 13 publications

Sodium‐Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes

Sodium‐Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes

Lymphatic dysfunction in advanced cirrhosis: Contextual perspective and clinical implications

Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease

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