Faculty Opinions recommendation of Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Abstract Introduction: Treatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction.Methods: Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size.Result: In a pooled population of 615 patients—297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), -0.56, 95%CI, - 0.88 to -0.25, P<0.01], aspartate aminotransferase (SDM, -0.44, SE, 95%CI, -0.64 to -0.24, P<0.01), gamma glutaryl transaminase (SDM, -0.59, 95%CI, -0.86 to -0.34, P<0.01) and reduction in liver fat content (LFC) (SDM, -0.43, 95%CI, - 0.74 to -0.13, P<0.01), as well as glycosylated haemoglobin (SDM, -0.40, 95% CI, -0.61 to -0.19, P<0.01) and weight (SDM, -0.66, 95% CI, -0.88 to -0.45, P<0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.59, 95%CI, 2.67 to 16.29, P<0.01). Conclusion: This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducie body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824)

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Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018817741852 ◽

2017 ◽

Vol 9 (1) ◽

pp. 15-28 ◽

Cited By ~ 15

Author(s):

Elizabeth P. Mills ◽

K. Paige D. Brown ◽

Jennifer D. Smith ◽

Phillip W. Vang ◽

Katie Trotta

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Efficacy And Safety ◽

Nonalcoholic Fatty Liver

Objective: To review current literature for the efficacy and safety of treatment for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to June 2017 was conducted using the search terms nonalcoholic fatty liver disease, diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin. Bibliographies of chosen articles were reviewed. Study selection and data extraction: Relevant articles on metformin, thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and statins for the treatment of NAFLD which included patients with T2DM were reviewed. A total of 23 relevant studies were found and included randomized controlled, observational, and open-label designs, as well as three meta-analyses. Data synthesis: Metformin combined with weight loss provides a modest improvement in steatosis and no improvement in fibrosis in patients with NAFLD and T2DM. TZDs showed positive results on fibrosis and resolution of NASH but at least half of patients studied were nonresponders. GLP-1 RAs also showed favorable results on reductions in transaminases and steatosis and improvements in insulin sensitivity and weight loss but lack efficacy data for resolution of NASH or improvement in fibrosis scores. Statins showed favorable results on reductions in transaminases but mixed results for improvement in steatosis and fibrosis scores. Conclusion: All reviewed treatment options are safe for management of NAFLD in patients with T2DM but long-term histological improvements are minimal. TZDs are efficacious for resolution of NASH and improvements in fibrosis but long-term use is required to maintain these results.

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Efficacy and safety of ezetimibe/simvastatin combination therapy in patients with type 2 diabetes and nonalcoholic fatty liver disease

Orvosi Hetilap ◽

10.1556/oh.2009.28624 ◽

2009 ◽

Vol 150 (21) ◽

pp. 989-993 ◽

Cited By ~ 7

Author(s):

Tatjána Ábel ◽

János Fehér ◽

Elek Dinya ◽

Mohamed Gamal Eldin ◽

Attila Kovács

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Combination Therapy ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Efficacy And Safety ◽

Nonalcoholic Fatty Liver

A nem alkoholos zsírmáj gyakran fordul elő a metabolikus szindrómához tartozó 2-es típusú diabetesben, dyslipidaemiában és obesitasban. Célkitűzés: Az ezetimib/simvastatin 10/20 mg kombinált kezelés hatékonyságának és biztonságosságának meghatározása 2-es típusú diabeteses és nem alkoholos zsírmájú betegek esetében. Módszer: Tizenkilenc 2-es típusú diabeteses és nem alkoholos zsírmájú beteget vizsgáltunk, akiket 2005 és 2008 között diagnosztizáltak és kezeltek a Budaörsi Egészségügyi Központban. Hat hónappal az ezetimib/simvastatin (10/20 mg naponta) kombinált kezelést követően minden betegnél megfigyeltük a szérum-alanin-aminotranszferáz- (ALT-), aszpartát-aminotranszferáz- (AST-), koleszterin-, LDL-koleszterin-, HDL-koleszterin- és trigliceridszint változását. Eredmények: Hat hónappal az ezetimib/simvastatin adását követően szignifikánsan csökkent az ALT (63,78±5,12 vs. 32,57±3,92 U/L; p < 0,0001), az AST (50,79±3,66 vs. 23,68±3,42 U/L; p < 0,0001), a koleszterin (6,26±0,46 vs. 4,02±0,31 mmol/L; p < 0,0001) és az LDL-koleszterin (4,24±0,37 vs. 2,22±0,1 mmol/L; p < 0,0001) koncentrációja. A kombinált kezelés szignifikánsan csökkentette a triglicerid szintjét (2,62±0,48 vs. 1,33±0,20 mmol/L; p < 0,0001) és növelte a HDL-koleszterin (1,02±0,12 vs. 1,18±0,07 mmol/L; p < 0,0001) koncentrációját. Következtetések: Vizsgálatunk eredményei azt mutatják, hogy az ezetimib/simvastatin kombinált kezelés biztonságos és hatékony 2-es típusú diabeteses, nem alkoholos zsírmájú betegek esetében.

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A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D)

Scientific Reports ◽

10.1038/s41598-021-01663-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samit Ghosal ◽

Debasis Datta ◽

Binayak Sinha

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Receptor Agonist ◽

Meta Analysis ◽

Nonalcoholic Fatty Liver ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

AbstractTreatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction. Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. In a pooled population of 615 patients—297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), − 0.56, 95% CI − 0.88 to − 0.25, P < 0.01], aspartate aminotransferase (SDM, − 0.44, SE, 95% CI − 0.64 to − 0.24, P < 0.01), gamma glutaryl transaminase (SDM, − 0.60, 95% CI − 0.86 to − 0.34, P < 0.01) and reduction in liver fat content (LFC) (SDM, − 0.43, 95% CI − 0.74 to − 0.12, P < 0.01), as well as glycosylated haemoglobin (SDM, − 0.40, 95% CI, − 0.61 to − 0.19, P < 0.01) and weight (SDM, − 0.66, 95% CI, − 0.88 to − 0.44, P < 0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.60, 95% CI 2.67 to 16.29, P < 0.01). This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducing body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824).

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THE EFFICACY AND SAFETY OF VILDAGLIPTIN TREATMENT FOR NONALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES MELLITUS

Cumhuriyet Medical Journal ◽

10.7197/cmj.835387 ◽

2020 ◽

Author(s):

Ahmet AKTAŞ ◽

Zeynep OZAN

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Efficacy And Safety ◽

Nonalcoholic Fatty Liver

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427-P: Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events in Patients with Established Cardiovascular Disease

Diabetes ◽

10.2337/db20-427-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 427-P

Author(s):

CHRISTOPH H. SAELY ◽

ALEXANDER VONBANK ◽

MAXIMILIAN MAECHLER ◽

BARBARA LARCHER ◽

LUKAS SPRENGER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Cardiovascular Events ◽

Nonalcoholic Fatty Liver ◽

Mutually Independent

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Systematic Review with Meta-Analysis: Response to Pioglitazone in Patients with Nonalcoholic Fatty Liver Disease with or Without Type 2 Diabetes

SSRN Electronic Journal ◽

10.2139/ssrn.3728783 ◽

2020 ◽

Author(s):

Zeyu Wang ◽

Huiqing Du ◽

Cuihua Ma ◽

Hongyu Chen ◽

Yong Jiang

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Meta Analysis ◽

Nonalcoholic Fatty Liver

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Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

International Journal of Hepatology ◽

10.1155/2012/950693 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Kei Nakajima

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Lipid Lowering ◽

Nonalcoholic Fatty Liver ◽

Ras Blockers

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

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