Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map

Kumar, Jai; Memon, Roha Saeed; Shahid, Izza; Rizwan, Tehlil; Zaman, Maryam; Menezes, Ritesh G.; Kumar, Sarwan; Siddiqi, Tariq Jamal; Usman, Muhammad

doi:10.1016/j.dld.2020.08.021

Cited by 60 publications

(53 citation statements)

References 21 publications

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“…We found a systematic review by Dougherty et al 25 reported SGLT2 inhibitors improved liver histology in patients with NASH according to findings from a single-arm clinical trial (table 2). However, the recent systematic review by Kumar et al 21 demonstrated SGLT2 inhibitors may not reduce liver fibrosis (standard mean difference: −0.07, 95% CI −0.33 to 0. 19).…”

Section: Changes In Liver Histology Liver Cancer and Liver Cirrhosismentioning

confidence: 99%

“…Qualitative findings of included systematic reviews indicated that SGLT2 inhibitors could effectively reduce these liver parameters in patients with NAFLD, compared with the placebo and other active comparators. However, the meta-analysis by Kumar et al 21 showed that, to achieve significance, SGLT2 inhibitors could decrease ALT and GGT levels by −16.17 U/L (95% CI −21.74 to −10.60) and −19.31 (95% CI −21.13 to −17.49) while yielding no statistical difference in AST reduction (−7.09 U/L, 95% CI −17.03 to 2.85). Notably, moderate to high heterogeneity among the clinical trials of SGLT2 inhibitors and ALT/AST evaluations was found.…”

Section: Changes In Liver Enzymesmentioning

confidence: 99%

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SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews

Shao

Kuo

Chien

et al. 2020

BMJ Open Diab Res Care

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IntroductionSodium glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver functions in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). The aim of this study is to critically appraise existing systematic reviews in order to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for patients with T2D with NAFLD.MethodsThis umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and September 16, 2020. Two independent investigators appraised study quality using AMSTAR2 (Assessment of Multiple Systematic Reviews 2). The hepatic effects from SGLT2 inhibitors were summarized based on liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer.ResultsOf 25 screened potential systematic reviews, we ultimately included 7 in this study. However, none of them could be rated as being of high methodological quality. Five systematic reviews indicated that SGLT2 inhibitors could effectively decrease liver fat and liver parameters of alanine aminotransferase and gamma-glutamyl transferase in patients with NAFLD. Two systematic reviews indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy-proven evidence of improvement from a small clinical trial, but no evidence of liver fibrosis improvement was found.ConclusionsThere is some association between SGLT2 inhibitor use and observed benefits to liver functions in patients with T2D with NAFLD, although the quality of current systematic reviews remains relatively low. Further evaluation of long-term liver outcomes with SGLT2 inhibitors in cases of liver cirrhosis and liver cancer is warranted.

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Section: Changes In Liver Histology Liver Cancer and Liver Cirrhosismentioning

confidence: 99%

Section: Changes In Liver Enzymesmentioning

confidence: 99%

SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews

Shao

Kuo

Chien

et al. 2020

BMJ Open Diab Res Care

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“…Thiazolidinediones have also been shown to improve ibrosis in NASH patients when compared to placebo, however it has not been seen in all studies to a signi icant extent [64][65][66]. A recent meta-analysis of 26 studies concluded that pioglitazone was associated with reductions in both AST and ALT and improved steatosis in both diabetic and non-diabetic NAFLD patients [67]. Pioglitazone is not without risk, it is well known to have a decently-sized side-effect pro ile ranging from weight gain, increased cardiovascular events, luid retention, and increased risk for bone fractures in women [40,67,68].…”

Section: Thiazolidinedionesmentioning

confidence: 99%

“…A recent meta-analysis of 26 studies concluded that pioglitazone was associated with reductions in both AST and ALT and improved steatosis in both diabetic and non-diabetic NAFLD patients [67]. Pioglitazone is not without risk, it is well known to have a decently-sized side-effect pro ile ranging from weight gain, increased cardiovascular events, luid retention, and increased risk for bone fractures in women [40,67,68]. While there is no inalized recommendation on dosing of pioglitazone, some groups recommend a safe starting dose of 15 mg per day titrating up to 30 mg per day for histologic improvement [65,66,68].…”

Section: Thiazolidinedionesmentioning

confidence: 99%

Non-alcoholic fatty liver disease: Update on treatment options and translational implications of sleep disruption

D’Souza¹,

Yoo²,

Houston³

et al. 2021

Ann Clin Gastroenterol Hepatol

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Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated with sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver. A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation. Core tip The pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.

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“…При сравнении влияния пиоглитазона на структурное состояние печени с другими сахароснижающими препаратами (агонисты глюкагоноподобного пептида-1, ингибиторы натрий-глюкозного котранспортера 2-го типа, ингибиторы дипептидилпептидазы-4) выявлено его положительное влияние на пациентов с НАЖБП. Поскольку пиоглитазон снижает ИР, липотоксичность и положительно влияет на атеросклеротические ССЗ, он обладает значительными преимуществами в отношении НАЖБП и НАСГ, в том числе в отношении печеночных трансаминаз [18] (табл. 1).…”

Section: влияние пиоглитазона на стеатогепатит/ неалкогольную жировую болезнь печениunclassified

Pioglitazone is a forgotten hypoglycemic drug with proven cardioprotective and nephroprotective properties

Pesheva¹,

Фадеев²

2021

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Considering that type 2 diabetes mellitus is a multicomponent disease and is associated with an extremely high risk of macrovascular complications (myocardial infarction, stroke and death from cardiovascular diseases), at present, much attention is paid to the choice of hypoglycemic drugs, given the individual characteristics of the patient. Preference is given to drugs of those classes that have a positive effect on cardiovascular outcomes. Along with relatively new molecules (inhibitors of the sodium-glucose cotransporter type 2 and agonists of glucagon-like peptide-1 receptors), the well-known drug pioglitazone, which belongs to the thiazolidinediones group, has not left the field of attention of researchers. Importantly, the cardioprotective effect of pioglitazone has been confirmed in several large randomized trials that showed a delay in atherosclerosis and a reduced risk of cardiovascular disease (PERISCOPE, CHICAGO, IRIS and PROactive). As an insulin sensitizer, pioglitazone reduces insulin resistance, has a protective effect on pancreatic β-cells, and also has a beneficial effect on components of insulin resistance syndrome (lowers blood pressure, lipid spectrum parameters) and improves the course of non-alcoholic fatty liver disease. There is evidence of possible side effects (weight gain, fluid retention, fractures), but their severity decreases with decreasing dose of the drug.

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Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map

Cited by 60 publications

References 21 publications

SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews

SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews

Non-alcoholic fatty liver disease: Update on treatment options and translational implications of sleep disruption

Pioglitazone is a forgotten hypoglycemic drug with proven cardioprotective and nephroprotective properties

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