Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women

Tiikkainen, Mirja; Bergholm, Robert; Rissanen, Aila; Aro, Antti; Salminen, Irma; Tamminen, Marjo; Teramo, Kari; Yki‐Järvinen, Hannele

doi:10.1093/ajcn/79.1.22

Cited by 73 publications

(33 citation statements)

References 58 publications

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“…cation alone. 5,9 Our data confirm the prior findings, and suggest that 9 months of therapy can result in a loss of about 8% body weight. Inhibition of fat absorption with the use of orlistat can favorably impact serum lipid levels, 15 and in this study, we found improved levels of cholesterol and LDL cholesterol (Table 3).…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, weight loss of as little as 6%-8% has been shown to improve insulin sensitivity, and intra-abdominal and hepatic steatosis. 3,9,10 Data specific to NASH subjects is limited to small trials with incomplete histologic follow-up. A pilot trial of 15 subjects treated for 12 months with a 1,400 calorie/day diet consisting of 40%-45% carbohydrate, 35%-40% fat, and 15%-20% protein showed that a weight loss of 7% improved the total NASH score and steatosis.…”

Section: Discussionmentioning

confidence: 99%

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Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Fecht²,

et al. 2008

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The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index ‫؍‬ >27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 ؎ 9.0 (standard deviation) years and mean body mass index was 36.4 ؎ 6.3 kg/m 2 . Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >5% body weight (n ‫؍‬ 24) compared to <5% body weight (n ‫؍‬ 17) correlated with improvement in insulin sensitivity (P ‫؍‬ 0.001) and steatosis (P ‫؍‬ 0.015). Comparing subjects who lost >9% of body weight (n ‫؍‬ 16), to those that did not (n ‫؍‬ 25), improved insulin sensitivity (P < 0.001), adiponectin (P ‫؍‬ 0.03), steatosis (P ‫؍‬ 0.005), ballooning (P ‫؍‬ 0.04), inflammation (P ‫؍‬ 0.045), and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >9% also achieved improved hepatic histologic changes. (HEPATOLOGY 2009;49:80-86.)

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Fecht²,

et al. 2008

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“…The reproducibility of repeated measurements of subcutaneous and intra-abdominal fat as determined on two separate occasions in our laboratory in nondiabetic subjects are 3 and 5% (25). Liver fat was measured with proton spectroscopy as previously described (26). The reproducibility of repeated measurement of liver fat in nondiabetic subjects studied on two occasions in our laboratory is 11% (25).…”

Section: Methodsmentioning

confidence: 95%

Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes

et al. 2004

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Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 ؎ 3 years, fasting plasma glucose 152 ؎ 9 mg/dl, BMI 30.6 ؎ 0.8 kg/m 2 ) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA 1c , insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 ؎ 4 vs. 82 ؎ 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 ؎ 3 vs. 7 ؎ 1%, 0 vs. 16 weeks, P ‫؍‬ 0.003) but not by metformin (13 ؎ 3 to 14 ؎ 3%, NS). Rosiglitazone (16 ؎ 2 vs. 20 ؎ 1 ml ⅐ kg ؊1 ⅐ min ؊1, P ‫؍‬ 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r ‫؍‬ ؊0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator-activated receptor-␥, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake.

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“…This fact is explained by the 25% reduction on the intestinal cholesterol absorption induced by the drug 25 . Diminution on intestinal lipid flux has been related to a decrease in the intra-abdominal fat content, 44% over the observed with a comparable weight reduction induced by diet alone 26,27 . Other beneficial effects secondary to the weight reduction induced by orlistat include the C-reactive protein, postprandial lipaemia, atherogenic lipoproteins and adipokines (interleukin-6 and a-tumour necrosis factor) reduction as well as adiponectin augment 28,29 .…”

Section: Cardiovascular Risk Factorsmentioning

confidence: 91%

Drugs in the treatment of obesity: sibutramine, orlistat and rimonabant

Rubio

Gargallo²,

Millán

et al. 2007

Public Health Nutr.

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Background: Modification of lifestyle is the main therapeutical approach in the treatment of obesity, but use to fail on long terms of time. Addition of anti-obesity drugs allows keeping the weight loss during years and improving obesity-related comorbidities. Methods: This review is an actualisation on efficacy, safety and tolerability of the approved drugs on the long-term treatment of obesity (orlistat and sibutramine). New indications and effects of their use far beyond the weight loss are as well commented. Finally, potential benefits of the administration of CB1 antagonist rimonabant on the weight loss and cardiometabolic risk factors are analysed in detail. Discussion: A decade of experience on the use of orlistat and sibutramine has demonstrated their higher efficacy on the weight loss when compared to placebo either on adult or teenage population as well as safety and tolerability on longterm administration. Beneficial effects on the lipid profile, glycosilated haemoglobin on diabetic patients, blood pressure and levels of inflammatory cytokines, contribute to decrease the cardiovascular risk on obese patients. Phase III clinical trials using rimonabant show additional benefits to the expected weight loss, mainly reducing visceral fat and cardiometabolic risk factors. Conclusion: Pharmacological treatment of obesity must be considered as a therapeutical tool that has to be used together with long-term lifestyle changes, contributing to the body weight reduction as well as to the improvement of the cardiometabolic risk related to obesity.

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Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women

Cited by 73 publications

References 58 publications

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes

Drugs in the treatment of obesity: sibutramine, orlistat and rimonabant

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