Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: Think out of the box!

Ranjbar, Golnaz; Mikhailidis, Dimitri P.; Sahebkar, Amirhossein

doi:10.1016/j.metabol.2019.154001

Cited by 75 publications

(80 citation statements)

References 123 publications

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“…SGLT2 inhibitors, including dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, and luseogliflozin are being used increasingly in the treatment of T2DM; they promote weight loss which is an attractive property for the treatment of patients with NAFLD. Although SGLT2 inhibitors are not yet generally recommended for the treatment of NAFLD in patients with T2DM, emerging data suggest that SGLT2 inhibitors reduce the risk of progression of NAFLD [ 112 ], as the following results have been reported: a decrease in hepatic fat content [ 113 114 ]; a decrease in AST and ALT [ 114 115 ]; a decrease in the measures of fibrosis, such as the FIB-4 index [ 115 116 ], the fibrosis index calculated from hyaluronic acid and type IV collagen 7S [ 116 ], and VCTE-measured LSM [ 117 ]; an improvement in hepatic insulin sensitivity [ 114 ]; and histology [ 118 ]. Well-designed RCTs are needed to elucidate whether SGLT2 inhibitors should be used as the first-line drug choice in patients with NAFLD/NASH with T2DM.…”

Section: Treatment Of Nafldmentioning

confidence: 99%

“…GLP-1 RAs, including exenatide, lixisenatide and liraglutide, are promising candidates for the treatment of NAFLD and NASH because they can reduce weight and enhance insulin action. However, GLP-1 RAs are not generally recommended for the treatment of NAFLD in patients with T2DM because of the limited data to date [ 112 ]. In a well-performed clinical trial in patients with biopsy-proven NASH, liraglutide (1.8 mg daily) treatment for 48 weeks was associated with greater resolution of steatohepatitis and less progression of fibrosis [ 120 ].…”

Section: Treatment Of Nafldmentioning

confidence: 99%

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Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association

Lee

Park

et al. 2020

Diabetes Metab J

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This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

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Section: Treatment Of Nafldmentioning

confidence: 99%

Section: Treatment Of Nafldmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association

Lee

Park

et al. 2020

Diabetes Metab J

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“…Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is a new class of glucose-lowering agents, which have additional benefits in patients with NAFLD/NASH through weight loss, increasing insulin sensitivity and even a direct effect on suppression of lipogenesis in hepatocytes (36). Liraglutide was studied in different doses starting from 0.3 mg to 3 mg/day, and it improved biological and clinical parameters i.e.…”

Section: Anti-diabetic Agents Targeting Nafldmentioning

confidence: 99%

Non‑alcoholic fatty liver disease: A major challenge in type�2 diabetes mellitus (Review)

Bică¹,

Sandu²,

Suceveanu

et al. 2020

Exp Ther Med

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Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in type 2 diabetes mellitus (T2DM) patients, being one of the disorders with a relevant global burden. Cross-sectional studies have shown that patients with T2DM and NAFLD have a higher prevalence of liver fibrosis, compared with the general population. Patients with non-alcoholic steatohepatitis (NASH) and T2DM have an increased mortality and morbidity, therefore they generate substantial health care costs. NASH worsens chronic diabetes complications, and T2DM aggravate the NASH progression to fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). The objectives in NAFLD and NASH therapy are to reduce disease activity, to slow down progression of fibrosis, and to lower the risk factors. Unfortunately, there are no specific validated pharmacological therapies. Several trials have demonstrated that anti-diabetic agents such as thiazolidindiones, sodium-glucose co-transporter inhibitors, glucagon like peptide-1 receptor analogs, or dipeptidyl peptidase-4 inhibitors might have complimentary benefits for patients with NAFLD. Some of the effect on reducing steatosis and fibrosis is explained by the weight loss these treatments produce. A goal in standard care is developing screening tools, early and non-invasive diagnosis methods, studying the pleiotropic effects of drugs, together with newer therapeutic agents, which can target mutual pathogenic mechanisms for diabetes and liver disease. Contents 1. Introduction 2. NAFLD and insulin resistance-lipotoxicity and glucotoxicity 3. NAFLD evaluation and progression 4. Therapeutic management 5. Anti-diabetic agents targeting NAFLD 6. Conclusions

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“…10 Because of these metabolic risks, cardiovascular mortality is the most common reason for death in the NAFLD patient. 9-11…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: Think out of the box!

Cited by 75 publications

References 123 publications

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association

Non‑alcoholic fatty liver disease: A major challenge in type�2 diabetes mellitus (Review)

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

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