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Liraglutide hepatic steatosis

Kirstine S Tølbøl, Maria Nb Kristiansen, Henrik H Hansen, Sanne S Veidal, Kristoffer Tg Rigbolt, Matthew P Gillum, Jacob Jelsing, Niels Vrang, Michael Feigh
AIM: To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis (NASH) in obese mouse models of biopsy-confirmed NASH. METHODS: Male wild-type C57BL/6J mice (DIO-NASH) and Lep ob/ob ( ob/ob -NASH) mice were fed a diet high in trans-fat (40%), fructose (20%) and cholesterol (2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score (NAS) and fibrosis staging system...
January 14, 2018: World Journal of Gastroenterology: WJG
Joan Khoo, John Hsiang, Ranu Taneja, Ngai-Moh Law, Tiing-Leong Ang
We compared the effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m(2) , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks...
May 14, 2017: Diabetes, Obesity & Metabolism
Simona Cernea, Avivit Cahn, Itamar Raz
The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis. Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways...
May 2017: Expert Review of Clinical Pharmacology
Ryotaro Bouchi, Yujiro Nakano, Tatsuya Fukuda, Takato Takeuchi, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
Liraglutide, an analogue of human glucagon-like peptide 1, reduces cardiovascular events in patients with type 2 diabetes; however, it has still been unknown by which mechanisms liraglutide could reduce cardiovascular events. Type 2 diabetic patients with insulin treatment were enrolled in this randomized, open-label, comparative study. Participants were randomly assigned to liraglutide plus insulin (liraglutide group) and insulin treatment (control group) at 1:1 allocation. Primary endpoint was the change in viscera fat are (VFA, cm(2)) at 24 weeks...
March 31, 2017: Endocrine Journal
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Petra J W Pouwels, Indra C Pieters-van den Bos, Trynke Hoekstra, Michaela Diamant, Daniël H van Raalte, Djuna L Cahen
AIMS/HYPOTHESIS: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. METHODS: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62...
December 2016: Diabetologia
Qin He, Sha Sha, Lei Sun, Jing Zhang, Ming Dong
The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy...
August 5, 2016: Biochemical and Biophysical Research Communications
Matthew James Armstrong, Piers Gaunt, Guruprasad P Aithal, Darren Barton, Diana Hull, Richard Parker, Jonathan M Hazlehurst, Kathy Guo, George Abouda, Mark A Aldersley, Deborah Stocken, Stephen C Gough, Jeremy W Tomlinson, Rachel M Brown, Stefan G Hübscher, Philip N Newsome
BACKGROUND: Glucagon-like peptide-1 (GLP-1) analogues reduce hepatic steatosis, concentrations of liver enzymes, and insulin resistance in murine models of fatty liver disease. These analogues are licensed for type 2 diabetes, but their efficacy in patients with non-alcoholic steatohepatitis is unknown. We assessed the safety and efficacy of the long-acting GLP-1 analogue, liraglutide, in patients with non-alcoholic steatohepatitis. METHODS: This multicentre, double-blinded, randomised, placebo-controlled phase 2 trial was conducted in four UK medical centres to assess subcutaneous injections of liraglutide (1·8 mg daily) compared with placebo for patients who are overweight and show clinical evidence of non-alcoholic steatohepatitis...
February 13, 2016: Lancet
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, Indra C Pieters, Djuna L Cahen, Michaela Diamant, Daniël H van Raalte
INTRODUCTION: Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis...
November 19, 2015: BMJ Open
Huiting Gao, Zhigang Zeng, Han Zhang, Xiaoli Zhou, Lichang Guan, Weiping Deng, Lishu Xu
Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim of the present study was to investigate the beneficial effect of liraglutide on diet-induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the rats subjected to HFHC diet four weeks before sacrificing the animals...
2015: Biological & Pharmaceutical Bulletin
K Vinodraj, I M Nagendra Nayak, J Vikram Rao, Paul Mathai, N Chandralekha, B Nitasha, D Rajesh, T K Chethan
OBJECTIVES: To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats. MATERIALS AND METHODS: There were four groups of six rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received liraglutide 1.8 mg/kg subcutaneously 6 days before dexamethasone and 6 days during dexamethasone administration...
March 2015: Indian Journal of Pharmacology
Shi-Wei Zhou, Man Zhang, Min Zhu
Simple hepatic steatosis is the early stage of non‑alcoholic fatty liver disease and is recognized as a benign process. Previous studies show that glucagon‑like peptide‑1 has great potential in improving hepatic steatosis. Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes. Therefore, the present study aimed to determine the effects of liraglutide (LG) on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L‑02 cells were induced by incubating L‑02 cells with 1 mmol/l free fatty acid (FFA) mixture (oleic acid and palmitic acid at a molar ratio of 2:1) for 24 h...
November 2014: Molecular Medicine Reports
Satoru Yamazaki, Hiroaki Satoh, Tsuyoshi Watanabe
We investigated the effects of liraglutide on insulin sensitivity and glucose metabolism in male Wistar rats. The rats were fed a normal chow diet (NCD) or a 60% high-fat diet (HFD) for a total of 4 weeks. After 3 weeks of feeding, they were injected with liraglutide once a day for 7 days. Subsequently, euglycemic-hyperinsulinemic clamp studies were performed after fasting the animals for 8 hours. During the clamp studies on the NCD-fed rats, the glucose infusion rate required for euglycemia was significantly higher in the liraglutide group than in the control group...
September 2014: Endocrinology
Huiting Gao, Lishu Xu, Dongfeng Li, Lichang Guang, Weiping Deng
OBJECTIVE: To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS: Thirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α in the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA...
November 2013: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Daniel J Cuthbertson, Andrew Irwin, Chris J Gardner, Christina Daousi, Tej Purewal, Niall Furlong, Niru Goenka, E Louise Thomas, Valerie L Adams, Sudeep P Pushpakom, Munir Pirmohamed, Graham J Kemp
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT)...
2012: PloS One
M J Armstrong, D D Houlihan, I A Rowe, W H O Clausen, B Elbrønd, S C L Gough, J W Tomlinson, P N Newsome
BACKGROUND: Non-alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon-like peptide-1 analogues are licensed in T2D, yet little data exist on efficacy and safety in liver injury. AIM: To assess the safety and efficacy of 26-week liraglutide on liver parameters in comparison with active-placebo. METHODS: Individual patient data meta-analysis was performed using patient-level data combined from six 26-week, phase-III, randomised controlled T2D trials, which comprise the 'Liraglutide Effect and Action in Diabetes' (LEAD) program...
January 2013: Alimentary Pharmacology & Therapeutics
Jamie E Mells, Ping P Fu, Shvetank Sharma, Darin Olson, Lihong Cheng, Jeffrey A Handy, Neeraj K Saxena, Dan Sorescu, Frank A Anania
The aims of this study were designed to determine whether liraglutide, a long-acting glucagon-like peptide, could reverse the adverse effects of a diet high in fat that also contained trans-fat and high-fructose corn syrup (ALIOS diet). Specifically, we examined whether treatment with liraglutide could reduce hepatic insulin resistance and steatosis as well as improve cardiac function. Male C57BL/6J mice were pair fed or fed ad libitum either standard chow or the ALIOS diet. After 8 wk the mice were further subdivided and received daily injections of either liraglutide or saline for 4 wk...
January 15, 2012: American Journal of Physiology. Gastrointestinal and Liver Physiology
J Jendle, M A Nauck, D R Matthews, A Frid, K Hermansen, M Düring, M Zdravkovic, B J Strauss, A J Garber
AIM: The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). METHODS: These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) (LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7...
December 2009: Diabetes, Obesity & Metabolism
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