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Treatment of obesity and metabolic-associated fatty liver disease with a diet or orlistat: A randomized controlled trial.
Feng, X, Lin, Y, Zhuo, S, Dong, Z, Shao, C, Ye, J, Zhong, B
The American journal of clinical nutrition. 2023;117(4):691-700
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Metabolic-associated fatty liver disease (MAFLD) is characterised by excessive lipid accumulation in hepatocytes. Weight management by the treatment to target strategy through lifestyle intervention remains the primary approach for MAFLD treatment. The aim of this study was to compare the efficacy of a conventional energy-restricted diet (the control group), orlistat, and an experimental diet in the Asian population with obesity and MAFLD. This study was a prospective, open-label, monocentric randomised controlled study. Participants (n = 118) were randomly assigned to the control (n = 39), orlistat (n = 40), or experimental diet (n = 39) groups at a 1:1:1 allocation. Results showed that: - orlistat and the experimental diet were superior to lifestyle intervention in ameliorating liver steatosis [fatty liver]. - the experimental diet had an advantage over lifestyle intervention when patients adhered to the diet. - orlistat was superior to the experimental diet and lifestyle modifications in decreasing liver fat content. Authors conclude that more multicentre, large-scale, prospective studies are needed to verify the long-term efficacy and safety of the experimental diet and orlistat treatment in subjects with MAFLD.
Abstract
BACKGROUND Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance. OBJECTIVES This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD. METHODS A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction. RESULTS A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01). CONCLUSIONS Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.
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Improvements in health-related quality of life over 3 years with liraglutide 3.0 mg compared with placebo in participants with overweight or obesity.
Kolotkin, RL, Gabriel Smolarz, B, Meincke, HH, Fujioka, K
Clinical obesity. 2018;8(1):1-10
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Obesity is associated with reduced health-related quality of life affecting physical, psychological and social function and well-being. The aim of the study was to determine the durability of improvement of health-related quality of life in participants taking Liraglutide 3.0mg after 3 years. The study included participants with prediabetes who were overweight or obese and presented weight-related conditions (hypertension or dyslipidaemia). Results indicate that participants taking 3.0mg of liraglutide for 3 years saw improvements in obesity-specific and physical aspects of health-related quality of life, and health utility. However, it showed little effects on the mental components when compared to the placebo. Authors conclude that Liraglutide 3.0mg, together with diet and exercise, lead to weight loss in obesity which is linked with improved health related quality of life.
Abstract
Previously in the SCALE Obesity and Prediabetes trial, at 1 year, participants with obesity (or overweight with comorbidities) and prediabetes receiving liraglutide 3.0 mg experienced greater improvements in health-related quality of life (HRQoL) than those receiving placebo. The current study extends these findings by examining 3-year changes in HRQoL. HRQoL was assessed using the obesity-specific Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, as well as the Short-Form 36 v2 (SF-36) health survey. At 3 years, mean change (±standard deviation) in IWQOL-Lite total score from baseline for liraglutide (n = 1472) was 11.0 ± 14.2, vs. 8.1 ± 14.7 for placebo (n = 738) (estimated treatment difference [ETD] 3.4 [95% confidence interval (CI): 2.0, 4.7], P < 0.0001). Mean change in SF-36 physical component summary (PCS) score from baseline for liraglutide was 3.1 ± 7.3, vs. 2.6 ± 7.6 for placebo (ETD 0.87 [95% CI: 0.17, 1.6], P = 0.0156). Mean change in SF-36 mental component summary score did not significantly differ between groups. Both IWQOL-Lite total score and PCS score demonstrated an association between greater HRQoL improvement with higher weight loss. Liraglutide 3.0 mg was also associated with improved health utility (Short-Form-6D and EuroQol-5D, mapped from IWQOL-Lite and/or SF-36) vs. placebo. Liraglutide 3.0 mg, plus diet and exercise, is associated with long-term improvements in HRQoL with obesity or overweight with comorbidity vs. placebo.
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The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.
Paterson, BM, Lammers, KM, Arrieta, MC, Fasano, A, Meddings, JB
Alimentary pharmacology & therapeutics. 2007;26(5):757-66
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In a healthy gut, intestinal epithelial cells, with their tight junctions, allow controlled passage of gluten and other fragments. When integrity of this system is compromised, as in celiac disease (CD), an inappropriate immune response to environmental antigens (i.e. gluten) develops. This is called hyper-intestinal permeability or 'leaky gut'. AT-1001 is a protein derived from a Gram-negative bacteria called Vibrio cholera. AT-1001 inhibits leaky gut and appears to have an impact on autoimmunity, making it a potential candidate for the treatment of CD. This double-blind, randomised placebo controlled study aims to determine the safety and tolerability of 12 mg doses of AT-1001 in CD subjects challenged with gluten. Intestinal permeability (IP) (measured urinary lactulose-to-mannitol) is used as a measure of drug efficacy. Male and female in-patients (n=20) aged 18-59y with diagnosed CD, on gluten-free diets for 6 months+ were, on days 1 and 3, treated with 12mg AT-1001 or placebo, followed by a sham gluten challenge, followed by the intestinal permeability measure. On day 2 the sham gluten was replaced by gluten. Puddings (containing sham or gluten) were served to all participants by kitchen staff in singe-blind fashion. For day 2 to day 1 IP change, there was a 70% increase in IP in the placebo group (P = 0.041) and no increase in the drug group, confirming the effects of gluten exposure on IP and the protective effects of AT-1001. Adverse events were mild (n=49) or moderate (n=3). Both groups experienced diarrhoea (an expected symptom in CD patients after exposure to gluten) but the AT-1001 treated volunteers reported less diarrhoea than placebo (P=0.017) suggesting a protective effect for AT-1001. This data demonstrate that 12 mg AT-1001 was generally safe, well tolerated and effectively mitigated gluten-induced GI adverse effects in coeliac patients when compared to placebo. Interferon (IFN)-γ (a marker of immune activity after acute dietary gluten) increased on day 3 in both the placebo group and AT-1001 group, but less so in the AT-1001 group though the difference was not statistically significant (likely due to small sample size). AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure. Larger studies are required to further elucidate the effects of AT-1001.
Abstract
BACKGROUND Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae. AIM: To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten. METHODS An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy. RESULTS Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-gamma levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018). CONCLUSIONS AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.