Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study

Armstrong, Matthew J.; Gaunt, Piers; Aithal, Guruprasad P.; Barton, Darren; Hull, Diana; Parker, Richard; Hazlehurst, Jonathan; Guo, Kathy; Abouda, George; Aldersley, Mark; Stocken, Deborah; Gough, Stephen; Tomlinson, Jeremy W.; Brown, Rachel M.; Hübscher, Stefan G.; Newsome, Philip N.

doi:10.1016/s0140-6736(15)00803-x

Cited by 1,627 publications

(1,450 citation statements)

References 31 publications

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“…GLP‐1R agonists increase glucose‐induced insulin secretion, decrease glucagon secretion and hepatic glucose output, and promote satiety leading to weigh loss 22. A recent multicenter, double‐blind, randomized, placebo‐controlled phase 2 study assessed the efficacy of liraglutide 1.8 mg daily for 48 weeks in patients with NASH (the LEAN study) 23. NASH resolution was noted in a significantly higher proportion of patients who received liraglutide (39%) than those who were in the placebo arm (9%, P = 0.019).…”

Section: Nafld/nash‐specific Therapiesmentioning

confidence: 99%

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Alkhouri

Poordad

Lawitz

2018

Hepatology Communications

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Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance, which is the hallmark of type 2 diabetes (T2D). NAFLD is a known risk factor for developing T2D and has a very high prevalence in those with existing T2D. The diabetes spectrum includes several conditions from prediabetes to T2D to insulin‐dependent diabetes leading to macrovascular and microvascular complications. Similarly, NAFLD has a histologic spectrum that ranges from the relatively benign nonalcoholic fatty liver to the aggressive form of nonalcoholic steatohepatitis with or without liver fibrosis to nonalcoholic steatohepatitis‐cirrhosis leading to end‐stage liver disease. The management of T2D has witnessed significant changes over the past few decades with multiple new drug classes entering the treatment algorithm. Unfortunately, there are no U.S. Food and Drug Administration‐approved medications to treat NAFLD, and guidelines for the management of NAFLD are less established. However, the field of drug development in NAFLD has witnessed a revolution over the past 5 years with the establishment of a regulatory pathway for Food and Drug Administration approval; this has generated substantial interest from pharmaceutical companies. Several diabetes medications have been studied as potential treatments for NAFLD with promising results; moreover, drugs that target specific pathways that play a role in NAFLD development and progression are being developed at a rapid pace. Given the similarities between NAFLD and T2D in terms of pathogenesis, underlying risk factors, and disease spectrum, lessons learned from optimizing treatment for T2D can be extrapolated to the management of NAFLD. The aim of this review is to use the founding principles of the comprehensive type 2 diabetes management algorithm to optimize the management of NAFLD. (Hepatology Communications 2018;2:778‐785)

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Section: Nafld/nash‐specific Therapiesmentioning

confidence: 99%

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Alkhouri

Poordad

Lawitz

2018

Hepatology Communications

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“…Although there is not good evidence of GLP-1 receptor expression in the human liver, the safety and efficacy of liraglutide at a dose of 1.8 mg/day was recently tested in a small randomised clinical trial in patients with biopsy-confirmed NASH [58], as specified in the section below.…”

Section: Secreted Hepatokines and The Role Of Incretins And Glucagonmentioning

confidence: 99%

“…Considering that insulin resistance is the hallmark of NAFLD, drugs acting on glucose metabolism have long been considered for NAFLD treatment [35,58,[72][73][74][75][76][77][78][79][80]. Insulin sensitizers have been tested in several clinical trials of different duration.…”

Section: Drug Treatment Of Nafld With a Defined Impact On Glucose Metmentioning

confidence: 99%

“…Initial studies in NASH were carried out with the short-acting GLP-1Ra exenatide; in a pilot study it produced a positive effect on liver histopathology in three out of 8 cases [89]. The long-acting GLP-1Ra liraglutide has now completed a phase IIb trial, showing a significant positive effect on NASH remission, independent of the presence of diabetes [58]. The mechanism(s) might be mediated by improved insulin sensitivity and reduced hepatic de novo lipogenesis [90].…”

Section: Drug Treatment Of Nafld With a Defined Impact On Glucose Metmentioning

confidence: 99%

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Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Targher

Marchesini

Byrne

2016

Diabetes & Metabolism

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Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liverrelated mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractNonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.

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“…8,9 Several anti-diabetic therapies have been investigated in the treatment of NASH with varying success, including metformin, [10][11][12] rosiglitazone, 13,14 pioglitazone, [15][16][17] and liraglutide. 18 Sitagliptin is an oral antihyperglycemic agent that competitively inhibits the enzyme dipeptidyl peptidase 4 (DPP-4), which inactivates the hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) released in response to meals. By blocking GLP-1 and GIP breakdown, sitagliptin increases insulin secretion and suppresses glucagon release in the pancreas, 19 which lowers blood glucose levels and improves hemoglobin A1c (HbA1c).…”

Section: Introductionmentioning

confidence: 99%

949 Sitagliptin Versus Placebo in the Treatment of Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Cui¹,

Philo²,

Nguyen³

et al. 2016

Gastroenterology

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Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study

Abstract: Wellcome Trust, National Institute of Health Research, and Novo Nordisk.

Cited by 1,627 publications

References 31 publications

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

949 Sitagliptin Versus Placebo in the Treatment of Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

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