scholarly journals Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis

2020 ◽  
Vol 21 (6) ◽  
pp. 1907 ◽  
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Katsutoshi Tokushige ◽  
Miwa Kawanaka ◽  
Hideki Fujii ◽  
...  
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Body Weight Gain ◽  
Severe Form ◽  
Sglt2 Inhibitors ◽  
Glucagon Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Antidiabetic Therapy ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide 1

Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D is closely associated with nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D have extensively been established, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D.

scholarly journals Antidiabetic Therapy in the Treatment of NASH

2020 ◽  
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Katsutoshi Tokushige ◽  
Miwa Kawanaka ◽  
Hideki Fujii ◽  
...  
Keyword(s):  
Liver Disease ◽  
Body Weight Gain ◽  
Severe Form ◽  
Sglt2 Inhibitors ◽  
Glucagon Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Antidiabetic Therapy ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide 1

Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 55 (1) ◽  
pp. 65-79 ◽  
Author(s):  
John A. Dougherty ◽  
Erenie Guirguis ◽  
Krisy-Ann Thornby
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Dipeptidyl Peptidase ◽  
Sglt2 Inhibitors ◽  
Dipeptidyl Peptidase Iv ◽  
Nonalcoholic Fatty Liver ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). Data Sources: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. Study Selection and Data Extraction: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. Data Synthesis: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. Relevance to Patient Care and Clinical Practice: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. Conclusions: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.

scholarly journals New Medications in the Treatment of Nonalcoholic Steatohepatitis

2018 ◽  
Vol 53 (3) ◽  
pp. 146-147
Author(s):  
Scot Walker
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Severe Form ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes ◽  
Common Risk Factors ◽  
Approved Drugs

Nonalcoholic fatty liver disease, an accumulation of fat in the liver, is estimated to occur in almost 1 in 5 adults. With 2 of the most common risk factors being obesity and diabetes, its prevalence is growing. Nonalcoholic steatohepatitis is a more severe form of nonalcoholic fatty liver disease. There are currently no approved drugs to treat nonalcoholic steatohepatitis, but several drugs are being developed to treat this disease.

Efficacy and cardiovascular safety of SGLT2 Inhibitors

2020 ◽  
Vol 15 ◽  
Author(s):  
Cornelius James Fernandez ◽  
Abisha Graciano Nevins ◽  
Shasta Nawaz ◽  
Tahir Nazir ◽  
Fahmy W F Hanna
Keyword(s):  
Decision Process ◽  
Cardiovascular Events ◽  
Unmet Need ◽  
Clinical Decision ◽  
Sglt2 Inhibitors ◽  
Renal Protection ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

: Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and renal protection, with an expectation that an ideal diabetic drug should improve these end points. Moreover, an ideal drug should have weight lowering benefits. Recently published outcome trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically significant weight reduction. As a result, many recently published international guidelines have recommended SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular disease (CVD). In this review we will critically analyse the efficacy and cardiovascular (CV) safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision process.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Alessandro Mantovani ◽  
Graziana Petracca ◽  
Alessandro Csermely ◽  
Giorgia Beatrice ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Liver Fat ◽  
Controlled Trials ◽  
Liver Fat Content ◽  
Nonalcoholic Fatty Liver ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): −10.0 IU/L, 95%CI −12.2 to −7.79 IU/L; I2 = 10.5%) and gamma-glutamyltransferase levels (WMD: −14.49 IU/L, 95%CI −19.35 to −9.63 IU/L, I2 = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: −2.05%, 95%CI −2.61 to −1.48%; I2 = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD.

Pathological findings of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease

2016 ◽  
Vol 67 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Michiie Sakamoto ◽  
Hanako Tsujikawa ◽  
Kathryn Effendi ◽  
Hidenori Ojima ◽  
Kenichi Harada ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Pathological Findings ◽  
Nonalcoholic Fatty Liver

scholarly journals Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 730
Author(s):  
Moritz Peiseler ◽  
Frank Tacke
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Disease Progression ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Adaptive Immune System ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
New Treatment ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

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