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1.  Effects of a weight-reduction program with orlistat on serum leptin levels in obese women: A 12-week, randomized, placebo-controlled study 
Background: Leptin, which has been identified as an antiobesity hormone, regulates body weight by controlling food intake and energy expenditure via the hypothalamic-pituitary-gonadal axis. It appears that leptin may be an important factor in obesity management. Orlistat, a pancreatic lipase inhibitor, could reduce fat absorption and promote weight loss due to leptin metabolism.
Objective: The purpose of this study was to investigate the effects of orlistat therapy on serum leptin levels.
Methods: Obese women (body mass index [BMI], 30 kg/m2) aged 18 to 50 years were randomly assigned to receive 12 weeks of oral treatment with diet-orlistat (120 mg TID) (DO group) or diet-placebo (DP group). During the treatment period, patients were asked to eat a balanced diet of -1200 to 1600 kcal/d. Body composition was determined by bioelectrical impedance. Serum leptin levels were measured using radioimmunoassay at baseline and at study end.
Results: A total of 24 patients entered the study; 14 patients (mean [SE] BMI, 37.7 [1.1] kg/m2) received orlistat and 10 patients (mean [SE] BMI, 39.4 [1.3] kg/m2) received placebo. Compared with baseline, mean percentages of loss of body weight and fat mass after 12 weeks of treatment were significant in the DO group (9.1% and 14.8%, respectively; both P = 0.001) and in the DP group (9.5% and 17.6%; both P = 0.005). The between-group differences were not statistically significant. Mean (SE) serum leptin levels also decreased significantly after treatment in the DO group (16.2 [1.2] vs 9.0 [1.0] ng/mL; P = 0.001) and in the DP group (19.3 [2.1] vs 9.7 [1.4] ng/mL; P = 0.005). The between-group difference was not statistically significant.
Conclusions: In this study of obese women, orlistat treatment was associated with a similar decrease in body weight, fat mass, and serum leptin levels as placebo over a 12-week period. In this regard, short-term orlistat therapy may not provide an additional effect on serum leptin levels, and reduction in leptin levels were closely related to the decrease in fat mass.
doi:10.1016/S0011-393X(04)90025-2
PMCID: PMC4053149  PMID: 24936112
leptin; obesity; orlistat; pharmacotherapy
2.  Effects of orlistat plus diet on postprandial lipemia and brachial artery reactivity in normolipidemic, obese women with normal glucose tolerance: A prospective, randomized, controlled Study 
Background:
Postprandial lipemia (PPL) is an independent predictor of earlyatherosclerosis and coronary artery disease. It is defined as a postprandial triglyceride (TG) level ≥80% higher than the fasting level. Brachial arterial reactivity (BAR) is used to identify early-phase atherosclerosis. Data concerning whether orlistat improves PPL and endothelial function are lacking.
Objective:
The aim of this study was to determine the effects of orlistat on PPL and BAR in normolipidemic, obese women with normal glucose tolerance.
Methods:
This prospective, randomized, controlled study was conducted at Baskent University, Ankara, Turkey. Normolipidemic, obese women aged 18 to 65 years with normal glucose tolerance were eligible for screening. On screening, demographic information, anthropomorphic parameters (body mass index [BMI], waist circumference [WC], hip circumference, waist-hip ratio), BAR, laboratory test results (level of insulin resistance assessed using the homeostasis model assessment-insulin resistance [HOMA-IR] index, serum lipid profile, fasting plasma levels of glucose and insulin [FPI]), and oral fat-loading test results were recorded as baseline values. The primary end points were the effects of orlistat + diet on PPL (assessed using the AUC of TG) and BAR. Women found on screening to be PPL positive were randomly assigned in a 2:1 ratio to treatment with orlistat 120 mg TID plus low-calorie diet (600-kcal/d deficit; minimum, 1200 kcal/d) or low-calorie diet only (control) for 12 weeks. After 12 weeks, all of the above assessments were repeated, and AUC values for lipid parameters were calculated as secondary outcome measures. To assess tolerability and compliance, women were monitored by telephone each week and instructed to return every 4 weeks for clinic visits.
Results:
Twenty-seven women were identified as PPL positive and assigned to the orlistat + diet group (18 subjects) or the control group (9) (mean [SD] age, 45.9 [2.3] years; mean [SD] weight, 87.4 [2.5] kg; mean [SD] BMI, 36.0 [0.8] kg/m2). Treatment with orlistat + diet was associated with significantly greater changes from baseline compared with controls in WC (P= 0.003), fasting and postprandial serum TG levels (P = 0.012 and P < 0.001, respectively), FPI level (P = 0.001), and HOMA-IR index (P < 0.001). Logistic regression analysis found that 12 weeks of treatment with orlistat + diet was associated with a numeric, but statistically non-significant, 4.1-fold change in PPL, which was independent of reductions from baseline in weight and WC. Neither treatment was associated with significant changes from baseline in BAR. The prevalences of gastrointestinal symptoms previously found to be related to orlistat use were statistically similar between the orlistat + diet and control groups (9 [50.0%] vs 3 [33.3%] subjects).
Conclusions:
The results of this small study in normolipidemic, obesewomen with normal glucose tolerance suggest that 12 weeks of treatment with orlistat 120 mg/d plus low-calorie diet was associated with a numeric, but statistically nonsignificant, 4.1-fold change from baseline in PPL, which was independent of reductions from baseline in weight and WC. Treatment with orlistat + diet was associated with significant effects on WC, TG, and level of insulin resistance, but not BAR.
doi:10.1016/j.curtheres.2006.06.001
PMCID: PMC3966008  PMID: 24678093
postprandial lipemia; brachial reactivity; orlistat; obesity.
3.  Obesity in adults 
Clinical Evidence  2010;2010:0604.
Introduction
About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, cardiovascular disease, osteoarthritis, and some cancers. Fewer than 10% of overweight or obese adults aged 40 to 49 years revert to a normal body weight after 4 years. Nearly 5 million US adults used prescription weight-loss medication between 1996 and 1998, but one quarter of all users were not overweight.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in adults with obesity? What are the effects of bariatric surgery in adults with morbid obesity? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: bariatric surgery versus medical interventions; biliopancreatic diversion; diethylpropion; gastric bypass; gastric banding; mazindol; orlistat (alone and in combination with sibutramine); phentermine; rimonabant; sibutramine (alone and in combination with orlistat); sleeve gastrectomy; and vertical banded gastroplasty.
Key Points
About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, CVD, osteoarthritis, and some cancers. Fewer than 10% of overweight or obese adults aged 40 to 49 years revert to a normal body weight after 4 years.Nearly 5 million US adults used prescription weight-loss medication between 1996 and 1998, but one quarter of all users were not overweight.
Orlistat, phentermine, rimonabant, and sibutramine may promote modest weight loss (an additional 1-7 kg lost) compared with placebo in obese adults having lifestyle interventions, but they can all cause adverse effects. Sibutramine may be more effective at promoting weight loss compared with orlistat, although not in obese people with type 2 diabetes or hypertension.We don't know whether combining orlistat and sibutramine treatment leads to greater weight loss than with either treatment alone.We don't know whether diethylpropion and mazindol are effective at promoting weight loss in people with obesity.Orlistat has been associated with GI adverse effects.Phentermine has been associated with heart and lung problems.Sibutramine has been associated with cardiac arrhythmias and cardiac arrest. In January 2010, the European Medicines Agency suspended marketing authorisation of sibutramine in the European Union because of the increased risk of non-fatal myocardial infarctions and strokes.Rimonabant has been associated with an increased risk of psychiatric disorders.
Bariatric surgery (gastric bypass, vertical banded gastroplasty, biliopancreatic diversion, or gastric banding) may increase weight loss compared with no surgery in people with morbid obesity.
Compared with each other, we don't know whether gastric bypass, vertical banded gastroplasty, biliopancreatic diversion, or gastric banding is the most effective surgery or the least harmful. We don't know whether sleeve gastrectomy is effective. Bariatric surgery may result in loss of over 20% of body weight, which may be largely maintained for 10 years.Operative and postoperative complications are common, and on average 0.28% of people die within 30 days of surgery. Mortality may be as high as 2% in some high-risk populations. However, surgery may reduce long-term mortality compared with no surgery.
PMCID: PMC2907622
4.  Obesity in adults 
Clinical Evidence  2011;2011:0604.
Introduction
About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, cardiovascular disease, osteoarthritis, and some cancers. Fewer than 10% of overweight or obese adults aged 40 to 49 years revert to a normal body weight after 4 years. Nearly 5 million US adults used prescription weight-loss medication between 1996 and 1998, but one quarter of all users were not overweight.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in adults with obesity? What are the effects of bariatric surgery in adults with morbid obesity? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: bariatric surgery versus medical interventions, biliopancreatic diversion, diethylpropion, gastric bypass, gastric banding, mazindol, orlistat (alone and in combination with sibutramine), phentermine, sibutramine (alone and in combination with orlistat), sleeve gastrectomy, and vertical banded gastroplasty.
Key Points
About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, CVD, osteoarthritis, and some cancers. Fewer than 10% of overweight or obese adults aged 40 to 49 years revert to a normal body weight after 4 years.Nearly 5 million US adults used prescription weight-loss medication between 1996 and 1998, but one quarter of all users were not overweight.
Orlistat, phentermine, and sibutramine may promote modest weight loss (an additional 1–7 kg lost) compared with placebo in obese adults having lifestyle interventions, but they can all cause adverse effects. Sibutramine may be more effective at promoting weight loss compared with orlistat, although not in obese people with type 2 diabetes or hypertension.We don't know whether combining orlistat and sibutramine treatment leads to greater weight loss than with either treatment alone.We don't know whether diethylpropion and mazindol are effective at promoting weight loss in people with obesity.Orlistat has been associated with GI adverse effects.Phentermine has been associated with heart and lung problems.Sibutramine has been associated with cardiac arrhythmias and cardiac arrest. In January 2010, the European Medicines Agency suspended marketing authorisation of sibutramine in the European Union because of the increased risk of non-fatal myocardial infarctions and strokes.In October 2010, the FDA requested the withdrawal of sibutramine from the US market because of the increased risk of adverse cardiovascular events.Rimonabant has been associated with an increased risk of psychiatric disorders.
Bariatric surgery (gastric bypass, vertical banded gastroplasty, biliopancreatic diversion, or gastric banding) may increase weight loss compared with no surgery in people with morbid obesity.
Compared with each other, we don't know whether gastric bypass, vertical banded gastroplasty, biliopancreatic diversion, or gastric banding is the most effective surgery or the least harmful. We don't know whether sleeve gastrectomy is effective. Bariatric surgery may result in loss of >20% of body weight, which may be largely maintained for 10 years.Operative and postoperative complications are common, and on average 0.28% of people die within 30 days of surgery. Mortality may be as high as 2% in some high-risk populations. However, surgery may reduce long-term mortality compared with no surgery.
PMCID: PMC3217730  PMID: 21411021
5.  Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials  
Objective To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions.
Design Systematic review with meta-analysis.
Data sources Medline, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials.
Study selection Studies were identified through to January 2014. Randomised trials of interventions to maintain weight loss provided to initially obese adults (aged ≥18) after weight loss of ≥5% body weight with long term (≥12 months) follow-up of weight change (main outcome) were included.
Study appraisal and synthesis Potential studies were screened independently and in duplicate; study characteristics and outcomes were extracted. Meta-analyses were conducted to estimate the effects of interventions on weight loss maintenance with the inverse variance method and a random effects model. Results are presented as mean differences in weight change, with 95% confidence intervals.
Results 45 trials involving 7788 individuals were included. Behavioural interventions focusing on both food intake and physical activity resulted in an average difference of −1.56 kg (95% confidence interval −2.27 to −0.86 kg; 25 comparisons, 2949 participants) in weight regain compared with controls at 12 months. Orlistat combined with behavioural interventions resulted in a −1.80 kg (−2.54 to −1.06; eight comparisons, 1738 participants) difference compared with placebo at 12 months. All orlistat studies reported higher frequencies of adverse gastrointestinal events in the experimental compared with placebo control groups. A dose-response relation for orlistat treatment was found, with 120 mg doses three times a day leading to greater weight loss maintenance (−2.34 kg, −3.03 to −1.65) compared with 60 mg and 30 mg three times a day (−0.70 kg, 95% confidence interval −1.92 to 0.52), P=0.02.
Conclusions Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance.
doi:10.1136/bmj.g2646
PMCID: PMC4020585  PMID: 25134100
6.  Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet 
The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.
doi:10.2147/DMSO.S58786
PMCID: PMC4085306  PMID: 25061325
SGLT2; empagliflozin; sibutramine; obesity; rat; combination
7.  Obesity management: Update on orlistat 
Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults – at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003).
Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
PMCID: PMC2350121  PMID: 18200802
obese; weight; diet; orlistat; hypertension; cholesterol
8.  Taking Orlistat: Predicting Weight Loss over 6 Months 
Journal of Obesity  2010;2011:806896.
This study explored the predictors of weight loss following orlistat with a focus on both baseline variables and changes in beliefs and behaviours occurring over the course of taking the drug. Patients (n = 566) prescribed orlistat completed a questionnaire at baseline and after 6 months concerning their weight, beliefs and behaviours. By 6 months the majority had lost some weight and showed improvements in diet. Many had also stopped taking the drug and a large minority reported using it flexibly as a lifestyle drug. Those who lost most weight showed a decrease in beliefs in a medical solution, a decrease in unhealthy eating, an increased belief in treatment control and an increased belief that the unpleasant consequences are both due to their eating behaviour and just part of the drug. When taken with fatty food orlistat causes symptoms such as anal leakage and oily stools. These may encourage some patients to focus on the behavioural aspects of their weight problem thus promoting the dietary changes needed for both short and longer term weight loss. When prescribing orlistat, clinicians should encourage patients to see the consequences as an education as a means to promote the effectiveness of this form of medical management.
doi:10.1155/2011/806896
PMCID: PMC2989378  PMID: 21113309
9.  Risk of colorectal cancer after initiation of orlistat: matched cohort study 
Objective To examine the risk of colorectal cancer after orlistat initiation in the UK population.
Design Retrospective matched cohort study.
Setting Data from the UK Clinical Practice Research Datalink from September 1998 to December 2008.
Participants 33 625 adults aged 18 years or over who started treatment with orlistat; each orlistat initiator was matched to up to five non-initiators (n=160 347) on age, sex, body mass index, and calendar time.
Main outcome measures Associations between orlistat initiation and the risk of colorectal cancer, assessed by calculating hazard ratios with propensity score adjusted Cox proportional hazard models.
Results Of 193 972 patients with a median age of 47 (interquartile range 37-57) years, 77% were women and approximately 90% were obese (body mass index ≥30). Orlistat initiators were more likely to have a previous history of diabetes or hypertension and to receive prescriptions for anti-diabetes drugs, statins, and aspirin compared with non-initiators. In the intention to treat analysis, 57 colorectal cancer events were identified among orlistat initiators and 246 among non-initiators, with median follow-up times of 2.96 and 2.86 years, respectively. The calculated incidence rate of colorectal cancer per 100 000 person years was 53 (95% confidence interval 41 to 69) for orlistat initiators and 50 (44 to 57) for non-initiators. Orlistat initiation was not associated with a higher risk of colorectal cancer (adjusted hazard ratio 1.11, 95% confidence interval 0.84 to 1.47). Findings were robust in the as treated analyses and in patients who were aged 50 years or over, were morbidly obese, or had a history of diabetes.
Conclusions This study found no evidence of an increased risk of colorectal cancer after the initiation of orlistat. It is limited by the relatively short follow-up time, and the possibility of adverse effects of long term orlistat use on risk of colorectal cancer cannot be excluded.
doi:10.1136/bmj.f5039
PMCID: PMC3754767  PMID: 23982291
10.  Skeletal muscle structural lipids improve during weight-maintenance after a very low calorie dietary intervention 
Background
The objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action.
Methods
Nine obese subjects (BMI = 35.7 ± 1.0 kg/m2), who had completed an 8 weeks VLCD (weight-loss = -9.7 ± 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 ± 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo.
Results
HOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo.
Conclusion
The data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.
doi:10.1186/1476-511X-8-34
PMCID: PMC2735746  PMID: 19678948
11.  Biochemical and histological impact of Vernonia amygdalina supplemented diet in obese rats 
This study was carried out to evaluate the anti-obesity effect of Vernonia amygdalina Del. (VA) supplemented diet. VA leaf powder was fed at 5% and 15% to diet-induced obese rats for 4 weeks and its effect compared with orlistat (5.14 mg/kg p.o.), an anti-obesity drug. Food intake, body and organ weights, total body fat, some lipid components and amino transaminase activities in serum, hepatocytes and brain; as well as serum glucose, were measured during or at end of the study. Result showed respective decrease of 12.78% and 38.51% in body weight gain, of VA fed rats against 17.45% of orlistat at end of study (P < 0.05); but with no effect on food intake. Total body fat was lowered by 28.04% and 30.02% vs. obese control rats (CDC) (P < 0.05). Furthermore, serum triacylglycerol (TG), serum and brain total cholesterol (TCHOL), were down regulated at 15% VA supplementation (P < 0.05). Serum glucose which increased in obese rats by 46.26% (P < 0.05) vs. NC, indicating intolerance, was restored by VA (38.75% and 34.65%) and orlistat (31.80%) vs. CDC (P < 0.05). VA diet also exerted hepato-protection, via lowering serum alanine amino transaminase (ALT) (41.35% and 27.13%) and aspartate amino transaminase (AST) (17.09% and 43.21%) activities (P < 0.05). Orlistat had no effect on these enzymes. Histology of adipose tissue corroborated the changes on total body fat. We concluded that, diet supplemented with VA can attenuate dietary obesity as well as ameliorates the potential risks of hepato-toxicity and glucose intolerance associated with obesity.
doi:10.1016/j.sjbs.2012.05.003
PMCID: PMC3730893  PMID: 23961200
Vernonia amygdalina Del.; Adipose tissue; Histology; Total body fat; Lipid profile; Glucose intolerance; Diet-induced obesity
12.  Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for severe obesity 
The British Journal of General Practice  2013;63(607):e115-e124.
Background
There is no established primary care solution for the rapidly increasing numbers of severely obese people with body mass index (BMI) > 40 kg/m2.
Aim
This programme aimed to generate weight losses of ≥15 kg at 12 months, within routine primary care.
Design and setting
Feasibility study in primary care.
Method
Patients with a BMI ≥40 kg/m2 commenced a micronutrient-replete 810–833 kcal/day low-energy liquid diet (LELD), delivered in primary care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner), with structured food reintroduction and then weight-loss maintenance, with optional orlistat to 12 months.
Result
Of 91 patients (74 females) entering the programme (baseline: weight 131 kg, BMI 48 kg/m2, age 46 years), 58/91(64%) completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients commenced weight-loss maintenance omitting the food-reintroduction stage. Of the remaining 54, 37(68%) started and completed food reintroduction over a mean duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months, weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD = 11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a documented maintained weight loss of ≥15 kg at 12 months, six (7%) had a 10–15 kg loss, and 11 (12%) had a 5–10 kg loss. The indicative cost of providing this entire programme for wider implementation would be £861 per patient entered, or £2611 per documented 15 kg loss achieved.
Conclusion
A care package within routine primary care for severe obesity, including LELD, food reintroduction, and weight-loss maintenance, was well accepted and achieved a 12-month-maintained weight loss of ≥15 kg for one-third of all patients entering the programme.
doi:10.3399/bjgp13X663073
PMCID: PMC3553637  PMID: 23561690
healthcare economics and organizations; morbid obesity; orlistat; primary health care
13.  Pharmacological Approaches for Management of Child and Adolescent Obesity 
Overweight and obesity among children and adolescents continue to be a global public health epidemic. Current national data on childhood and adolescent obesity show alarming statistics of overweight and obese children and adolescents. This epidemic runs across various continents and affects various ethnic populations. The current weight management practices involve dietary modification, behavioral change therapies involving exercise, pharmacological therapy and surgical intervention. The purpose of this current review is to focus on pharmacological therapy i.e. role of sibutramine and orlistat in childhood and adolescent weight management. An open search of PUBMED database was made with search 'key words' such as 'orlistat' or 'sibutramine' or "pharmacological approaches" and "child obesity" and "adolescent obesity". This yielded a total of 20 articles. All of these articles have been summarized in the current review. Sibutramine functions by promoting satiety and increases energy expenditure by inhibiting reuptake of noradrenaline and serotonin. Most of the studies, reviews and trials conducted using sibutramine among adolescents and children show limited short-term efficacy. The long-term effects of sibutramine use are not yet studied due to the severity of its side-effects profile. Orlistat was approved by Food and Drug Administration for adolescent weight reduction. Despite its approval, it has a limited role in adolescent and pediatric obesity reduction due to the purported malabsorption of fat soluble vitamins and its side-effect profile. Obesity and adolescent weight management in present times mainly deals with dietary modification with superadded behavioral therapies promoting exercise. There is insufficient evidence as of now if these alone would cause adequate weight reduction and weight maintenance. Pharmacotherapy i.e use of drugs like sibutramine and orlistat has a limited role in the current fight against childhood and adolescent obesity. Extreme side-effects, close monitoring and lack of long-term studies involving these drugs, suggest questionable efficacy in current times. Future research studies involving pharmacological agents need to not only have immense scientific rigor during preliminary analyses but should also translate their efficacy in practical and clinical settings.
Keywords
Obesity; Overweight; Adolescents; Pharmacological; sibutramine; Orlistat
doi:10.4021/jocmr2010.05.288w
PMCID: PMC3104647  PMID: 21629521
14.  Postprandial Effect of Orlistat on the Peaking of Lipid Level After Sequential High Fat Meals 
Background
Postprandial lipemia has been found to be strongly associated with atherosclerosis due to its atherogenic and thrombogenic lipoprotein changes. This phenomenon occurs even in normal subjects especially after high fat meals. Orlistat, an anti- obesity drug, has been shown to address postprandial lipemia after a single high fat meal.
Objectives
To compare the effects of orlistat and placebo on the postprandial lipid levels after sequential high-fat meals in healthy individuals with normal fasting lipid levels.
Patients and Methods
Thirty-one healthy adult volunteers with normal fasting lipid levels were fed 50% fat meals (3 meals and 2 snacks of pre-weighted butter and bread). The subjects were blindly randomized to receive either placebo or orlistat 120 mg before each main meal. The outcome parameters were total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and very-low–density lipoprotein (VLDL) cholesterol levels measured at fasting (0 h) and every 2 h thereafter, until the sixteenth hour. Additionally, we estimated the lipid levels at the fifth and ninth hour.
Results
The non-orlistat group showed a significant postprandial rise in the levels of TG and VLDL, which began 4 h after breakfast (P < 0.05); this rise in levels was sustained until 9 h after breakfast for TG and up to 10 h after breakfast for VLDL. In contrast, only one significant rise in both TG and VLDL levels (at 4 h after breakfast) was noted in the orlistat group. The maximum mean difference from the baseline TG level for the orlistat group was lower than that for the non-orlistat group (0.22 mmol/L vs. 0.756 mmol/L, respectively). Similarly, the maximum mean difference from the baseline VLDL level from baseline in the orlistat group was only 0.099 mmol/L, which was lower than that in the non-orlistat group (0.588 mmol/L). LDL levels rose to a lesser extent in the orlistat group than in the non-orlistat group (0.268 vs. 0.362 mmol/L). The TC levels did not show a postprandial rise; instead, the levels reduced in both groups, with the orlistat group showing a higher reduction than the non-orlistat group (-0.288 vs. -0.188 mmol/L). The orlistat group did not show any significant differences in the HDL measurements.
Conclusions
Administration of orlistat abolished the significantly sustained postprandial rise of TG and VLDL levels in healthy individuals who were fed sequential 50% fat meals.
doi:10.5812/ijem.2920
PMCID: PMC3693615  PMID: 23843804
Orlistat; Lipids; Postprandial Lipemia; Fatty Meal; Cardiovascular Disease
15.  Sleep-related breathing disorders and gait variability: a cross-sectional preliminary study 
BMC Pulmonary Medicine  2014;14:140.
Background
Sleep-related breathing disorders (SRBDs) provoke cognitive and structural brain disorders. Because these disorders have been associated with unsafe gait characterized by an increase in stride-to-stride variability of stride time (STV), we hypothesised that SRBDs could be associated with an increased STV. The aim of this study was to examine the association between SRBDs and STV in French healthy older community-dwellers.
Methods
A total of 49 participants (mean age 69.6 ± 0.8years; 65.2% female) were included in this cross-sectional study. All participants, who were free of clinically diagnosed SRBDs before their inclusion, had a nocturnal unattended home-sleep assessment. There were separated in three group based on apnea + hypopnea index (AHI): AHI <15 defining the absence of SRBD, AHI between 15–30 defining mild SRBD, and AHI >30 defining moderate-to-severe SRBD. Coefficient of variation of stride time, which is a measure of STV, was recorded while usual walking using SMTEC® footswitches system. Digit span score was used as a measure of executive performance. Age, gender, body mass index (BMI), number of drugs daily taken, vision, proprioception, history of falls, depression symptoms, global cognitive functioning were also recorded.
Results
STV and BMI were higher in participants with mild SRBDs (P = 0.031 and P = 0.020) and moderate-to-severe SRBDs (P = 0.004 and P = 0.002) compared to non-SRBDs. STV positively correlated with AHI (P = 0.036). Lower (i.e., better) STV was associated with the absence of SRBDs (P = 0.021), while greater (i.e., worse) STV was associated with moderate-to-severe SRBD (P < 0.045) but not with mild SRBD (P > 0.06).
Conclusion
Our results show a positive association between STV and SRBDs, with moderate-to-severe SRBD being associated with greater gait variability. This association opens new perspectives for understanding gait disorders in older adults with SRBDs and opens the door to treatments options since SRBDs are potential treatable factors.
doi:10.1186/1471-2466-14-140
PMCID: PMC4146548  PMID: 25150985
Gait disorders; Sleep-related breathing disorders; Older adults
16.  Orlistat in the prevention of diabetes in the obese patient 
There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level.
PMCID: PMC2496972  PMID: 18561508
type 2 diabetes mellitus; prevention; diabesity; obesity; metabolic syndrome; orlistat
17.  Plasma Phospholipid Fatty Acid Concentration and Incident Coronary Heart Disease in Men and Women: The EPIC-Norfolk Prospective Study 
PLoS Medicine  2012;9(7):e1001255.
Kay-Tee Khaw and colleagues analyze data from a prospective cohort study and show associations between plasma concentrations of saturated phospholipid fatty acids and risk of coronary heart disease, and an inverse association between omega-6 polyunsaturated phospholipid fatty acids and risk of coronary heart disease.
Background
The lack of association found in several cohort studies between dietary saturated fat and coronary heart disease (CHD) risk has renewed debate over the link between dietary fats and CHD.
Methods and Findings
We assessed the relationship between plasma phospholipid fatty acid (PFA) concentration and incident CHD using a nested case control design within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40–79 years examined in 1993–1997 and followed up to 2009. Plasma PFA concentrations were measured by gas chromatography in baseline samples retrieved from frozen storage. In 2,424 men and women with incident CHD compared with 4,930 controls alive and free of cardiovascular disease, mean follow-up 13 years, saturated PFA (14:0, 16:0,18:0) plasma concentrations were significantly associated with increased CHD risk (odds ratio [OR] 1.75, 95% CI 1.27–2.41, p<0.0001), in top compared to bottom quartiles (Q), and omega-6 polyunsaturated PFA concentrations were inversely related (OR 0.77, 0.60–0.99, p<0.05) after adjusting for age, sex, body mass index, blood pressure, smoking, alcohol intake, plasma vitamin C, social class, education, and other PFAs. Monounsaturated PFA, omega-3 PFA, and trans PFA concentrations were not significantly associated with CHD. Odd chain PFA (15:0, 17:0) concentrations were significantly inversely associated with CHD (OR 0.73, 0.59–0.91, p<0.001, Q4 versus Q1). Within families of saturated PFA or polyunsaturated PFA, significantly heterogeneous relationships with CHD were observed for individual fatty acids.
Conclusions
In this study, plasma concentrations of even chain saturated PFA were found to be positively and omega-6 polyunsaturated PFA inversely related to subsequent coronary heart disease risk. These findings are consistent with accumulating evidence suggesting a protective role of omega-6 fats substituting for saturated fats for CHD prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Coronary heart disease (CHD) is a condition caused by a build-up of fatty deposits on the inner walls of the blood vessels that supply the heart, causing the affected person to experience pain, usually on exertion (angina). A complete occlusion of the vessel by deposits causes a heart attack (myocardial infarction). Lifestyle factors, such as diet (particularly one high in fat), contribute to causing CHD. There are different types of fat, some of which are thought to increase risk of CHD, such as saturated fat, typically found in meat and dairy foods. However, others, such as unsaturated fats (polyunsaturated and monounsaturated fats) found in foods such as vegetable oils, fish, and nuts, may actually help prevent this condition.
Why Was This Study Done?
Although there have been many studies investigating the role of different types of dietary fat in coronary heart disease, it is still not clear whether coronary heart disease can be prevented by changing the type of dietary fat consumed from saturated to unsaturated fats or by lowering all types of dietary fat. Furthermore, many of these studies have relied on participants recalling their dietary intake in questionnaires, which is an unreliable method for different fats. So in this study, the researchers used an established UK cohort to measure the levels of different types of fatty acids in blood to investigate whether a diet high in saturated fatty acids and low in unsaturated fatty acids increases CHD risk.
What Did the Researchers Do and Find?
The researchers used a selection of 10,000 participants (all men and women aged 40–79 years) from the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Blood samples from the selected participants taken at the start of the study in 1993–1997 were analyzed to determine levels of specific fatty acids. Participants were followed up till 2011. The researchers identified 2,424 participants who were subsequently diagnosed with CHD using death certificates and hospital discharge data and matched these with 4,930 controls who were still alive and free of known coronary disease. The researchers grouped the type of blood fatty acids identified in the blood samples into six families (even chain saturated fatty acid, odd chain saturated fatty acid, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid, monounsaturated fatty acid, and trans-fatty acid), which represented saturated and unsaturated fatty acids. Using statistical methods, the researchers then compared the risks of developing CHD between cases and controls by the concentration of fatty acid families after adjusting for age and sex and other factors, such as body mass index, physical activity, and smoking. Using these methods, the researchers found that there was no overall significant relationship between total blood fatty acid concentration and CHD but there was a positive association with increasing blood saturated fatty acid concentration after adjusting for other fatty acid concentrations, with an odds ratio of 1.83 comparing higher versus lower concentrations. This risk was attenuated after adjusting for cholesterol levels, indicating that much of the association between saturated fatty acid and CHD is likely to be mediated through blood cholesterol levels. In contrast, blood omega-6 poly-unsaturated fatty acid concentrations were associated with lower CHD risk. Blood monounsaturated fatty acids, omega-3 poly-unsaturated fatty acids, and trans-fatty acids were not consistently associated with CHD risk. The authors also noted that within families of fatty acids, individual fatty acids related differently to CHD risk.
What Do These Findings Mean?
These findings suggest that plasma concentrations of saturated fatty acids are associated with increased risk of CHD and that concentrations of omega-6 poly-unsaturated fatty acids are associated with decreased risk of CHD. These findings are consistent with other studies and with current dietary advice for preventing CHD, which encourages substituting foods high in saturated fat with n-6 polyunsaturated fats. The results also suggest that different fatty acids may relate differently to CHD risk and that the overall balance between different fatty acids is important. However, there are limitations to this study, such as that factors other than diet (genetic differences in metabolism, for example) may cause changes to blood fatty acid levels so a major question is to identify what factors influence blood fatty acid concentrations. Nevertheless, these findings suggest that individual fatty acids play a role in increasing or decreasing risks of CHD.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001255.
Information about the EPIC-Norfolk study is available
The American Heart Foundation provides patient-friendly information about different dietary fats as does Medline
The British Heart Foundation also provides patient-friendly information on heart conditions
doi:10.1371/journal.pmed.1001255
PMCID: PMC3389034  PMID: 22802735
18.  Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial 
Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome.
Methods
The objective of this study was to determine the relationships between dairy product or supplemental calcium intake with changes in the plasma lipidome and body composition during energy restriction. A secondary objective of this study was to explore the relationships among calculated macronutrient composition of the energy restricted diet to changes in the plasma lipidome, and body composition during energy restriction. Overweight adults (n = 61) were randomized into one of three intervention groups including a deficit of 500kcal/d: 1) placebo; 2) 900 mg/d calcium supplement; and 3) 3-4 servings of dairy products/d plus a placebo supplement. Plasma fatty acid methyl esters of cholesterol ester, diacylglycerol, free fatty acids, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine and triacylglycerol were quantified by capillary gas chromatography.
Results
After adjustments for energy and protein (g/d) intake, there was no significant effect of treatment on changes in weight, waist circumference or body composition. Plasma lipidome did not differ among dietary treatment groups. Stepwise regression identified correlations between reported intake of monounsaturated fat (% of energy) and changes in % lean mass (r = -0.44, P < 0.01) and % body fat (r = 0.48, P < 0.001). Polyunsaturated fat intake was associated with the % change in waist circumference (r = 0.44, P < 0.01). Dietary saturated fat was not associated with any changes in anthropometrics or the plasma lipidome.
Conclusions
Dairy product consumption or calcium supplementation during energy restriction over the course of 12 weeks did not affect plasma lipids. Independent of calcium and dairy product consumption, short-term energy restriction altered body composition. Reported dietary fat composition of energy restricted diets was associated with the degree of change in body composition in these overweight and obese individuals.
doi:10.1186/1743-7075-8-67
PMCID: PMC3204227  PMID: 21970320
19.  Randomized Clinical Trials of Weight-Loss Maintenance: A Review 
The problem of overweight and obesity has reached epidemic proportions in the U.S. and globally, and the high prevalence is due in part to the recidivism associated with weight-loss treatment. Approximately one third of lost weight is often regained in the first year after treatment and, at times, continues. Because a plethora of co-morbid diseases are associated with obesity, in particular, cardiovascular disease, hypertension and hyperlipidemia, clinicians and researchers have attempted to find useful strategies for maintaining weight loss. This review presents the findings from 42 randomized clinical trials of weight-loss maintenance from 1984 through 2007 utilizing interventions that include 1) the Internet, 2) strategies after a very-low-calorie diet, 3) pharmacotherapy, 4) behavioral strategies, 5) physical activity, and 6) alternative strategies. The results of the reviewed trials revealed that treatment with orlistat or sibutramine combined with dietary modification, caffeine or protein supplementation, consuming a diet lower in fat, adherence to physical activity routines, prolonged contact with participants, problem-solving therapy and the alternative treatment acupressure were efficacious in reducing weight regain after weight-loss treatment. The limitations of some studies may reduce the robustness of their findings, and future studies are necessary to replicate and support these results so that individuals are able to maintain weight loss and retain the health benefits associated with a lower weight.
doi:10.1097/01.JCN.0000317471.58048.32
PMCID: PMC2676575  PMID: 19114803
weight loss maintenance; weight loss; obesity; overweight
20.  Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide 
Objective:
Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.
Design:
A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.
Subjects:
A total of 564 adults (n=90–98 per group; body mass index 30–40 kg m−2) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90–95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007–April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.
Results:
From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7–8.0) more weight than those on placebo and 3.8 kg (1.6–6.0) more than those on orlistat (P⩽0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3–4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.
Conclusion:
Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
doi:10.1038/ijo.2011.158
PMCID: PMC3374073  PMID: 21844879
liraglutide; GLP-1 analog; weight loss
21.  Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults 
Background:
Liraglutide 3.0 mg, with diet and exercise, produced substantial weight loss over 1 year that was sustained over 2 years in obese non-diabetic adults. Nausea was the most frequent side effect.
Objective:
To evaluate routinely collected data on nausea and vomiting among individuals on liraglutide and their influence on tolerability and body weight.
Design:
A randomized, placebo-controlled, double-blind 20-week study with an 84-week extension (sponsor unblinded at 20 weeks, open-label after 1 year) in eight European countries (Clinicaltrials.gov: NCT00422058).
Subjects:
After commencing a 500-kcal/day deficit diet plus exercise, 564 participants (18–65 years, body mass index (BMI) 30–40 kg m−2) were randomly assigned (after a 2-week run-in period) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg), placebo or open-label orlistat (120 mg × 3 per day). After 1 year, participants on liraglutide/placebo switched to liraglutide 2.4 mg, and subsequently, to liraglutide 3.0 mg (based on 20-week and 1-year results, respectively).
Results:
The intention-to-treat population comprised 561 participants (n=90–98 per arm, age 45.9±10.3 years, BMI 34.8±2.7 kg m−2 (mean±s.d.)). In year 1, more participants reported ⩾1 episode of nausea/vomiting on treatment with liraglutide 1.2–3.0 mg (17–38%) than with placebo or orlistat (both 4%, P⩽0.001). Most episodes occurred during dose escalation (weeks 1–6), with ‘mild' or ‘moderate' symptoms. Among participants on liraglutide 3.0 mg, 48% reported some nausea and 13% some vomiting, with considerable variation between countries, but only 4 out of 93 (4%) reported withdrawals. The mean 1-year weight loss on treatment with liraglutide 3.0 mg from randomization was 9.2 kg for participants reporting nausea/vomiting episodes, versus 6.3 kg for those with none (a treatment difference of 2.9 kg (95% confidence interval 0.5–5.3); P=0.02). Both weight losses were significantly greater than the respective weight losses for participants on placebo (P<0.001) or orlistat (P<0.05). Quality-of-life scores at 20 weeks improved similarly with or without nausea/vomiting on treatment with liraglutide 3.0 mg.
Conclusion:
Transient nausea and vomiting on treatment with liraglutide 3.0 mg was associated with greater weight loss, although symptoms appeared tolerable and did not attenuate quality-of-life improvements. Improved data collection methods on nausea are warranted.
doi:10.1038/ijo.2013.149
PMCID: PMC4010971  PMID: 23942319
GLP-1 analog; liraglutide; nausea; quality of life; vomiting; weight loss
22.  Dietary intakes associated with successful weight loss and maintenance during the Weight Loss Maintenance Trial 
Background
Dietary components effective in weight maintenance efforts have not been adequately identified.
Objective
To determine impact of changes in dietary consumption on weight loss and maintenance during the Weight Loss Maintenance (WLM) clinical trial.
Design
WLM was a randomized controlled trial. Successful weight loss participants who completed Phase I of the trial and lost 4kg were randomized to one of three maintenance intervention arms in Phase II and followed for an additional 30 months.
Participants/setting
The multicenter trial was conducted from 2003–2007. This substudy included 828 successful weight loss participants.
Methods
Dietary Measures
The Block Food Frequency Questionnaire (FFQ) was used to assess nutrient intake levels and food group servings. Carbohydrates, proteins, fats, dietary fiber and fruit/vegetable and dairy servings were utilized as predictor variables.
Data collection
The FFQ was collected on all participants at study entry (beginning of Phase I). Those randomized to Phase II completed the FFQ at three additional time points; randomization (beginning of Phase II), 12 and 30 months.
Intervention
The main intervention focused on long term maintenance of weight loss using the Dietary Approaches to Hypertension (DASH) diet. This substudy examined whether changes to specific dietary variables were associated with weight loss and maintenance.
Statistical analyses performed
Linear regression models that adjusted for change in total energy examined the relationship between changes in dietary intake and weight for each time period. Site, age, race, sex, and a race-sex interaction were included as covariates.
Results
Participants who substituted protein for fat lost, on average, 0.33 kg per 6-months during Phase I (p<0.0001) and 0.07 kg per 6-months during Phase II (p<0.0001) per 1% increase in protein. Increased intake of fruits and vegetables was associated with weight loss in Phases I and II: 0.29 kg per 6-months (p<0.0001) and 0.04 kg per 6-months (p=0.0062), respectively, per 1-serving increase. Substitution of carbohydrates for fat and protein for carbohydrates were associated with weight loss during both phases. Increasing dairy intake was associated with significant weight loss during Phase II (−0.17 kg per 6-months per 1-serving increase, p=0.0002), but not in Phase I. Dietary fiber revealed no significant findings.
Conclusion
Increasing fruits, vegetables, and low-fat dairy may help achieve weight loss and maintenance.
doi:10.1016/j.jada.2011.09.014
PMCID: PMC3225890  PMID: 22117658
Weight Loss Maintenance Trial; dietary intakes; food frequency questionnaire
23.  Orlistat with behavioral weight loss for obesity with versus without binge eating disorder: Randomized placebo-controlled trial at a community mental health center serving educationally and economically disadvantaged Latino/as 
Behaviour research and therapy  2013;51(3):167-175.
Objective
This study was a randomized placebo-controlled trial testing the addition of orlistat to behavioral weight loss for obesity in Spanish-speaking-only Latino/as with versus without binge eating disorder (BED) performed at a community mental health center serving educationally- and economically-disadvantaged patients. Latino/as have high rates of obesity but are under-represented in obesity treatment studies and despite comparable-to-or-higher rates of BED than Whites, Latino/as are under-represented in BED treatment studies. BED is associated with obesity but whether it predicts/moderates treatment outcomes remains uncertain. Thus, this study also tested whether BED prospectively predicts/moderates outcomes.
Methods
Seventy-nine obese Spanish-speaking-only Latino/as with BED (N = 40) versus without BED (N = 39) at a community mental health center were randomly assigned to four-months of orlistat-plus-BWL or placebo-plus-BWL. BWL was culturally-enhanced modification of Diabetes-Prevention-Program delivered in weekly sessions in Spanish. Orlistat (120 mg tid) and matching-placebo delivered with standard clinical-management. Participants were assessed independently throughout treatment, post-treatment, and six-month follow-up.
Results
78% completed treatments; completion rates did not differ significantly by medication or BED. Intent-to-treat mixed-models analyses revealed significant improvements in binge eating, eating-psychopathology, and depression, and significant – albeit modest – weight-loss. Overall, the addition of orlistat to BWL was not associated with greater improvements; however, BED moderated weight-loss: orlistat-plus-BWL produced significantly greater weight-loss in non-BED group but not in BED. Improvements were maintained through 6-month follow-up; BED significantly predicted/moderated increases in eating concerns and depression following treatment. Within BED-group, binge-eating remission rates were 65% (post-treatment) and 50% (follow-up).
Conclusions
In this controlled trial performed at community mental health center serving educationally- and economically-disadvantaged Spanish-speaking-only Latino/as with co-morbid psychiatric needs, we observed outcomes for the BWL plus orlistat/placebo medication that approximate or are slightly dampened relative to the literature for efficacy trials with much more restrictive obese and BED samples. In this complex patient group, adding orlistat to BWL produced greater weight-loss than adding placebo among obese patients without BED but not among those with BED. Although 50% of BED patients maintained abstinence from binge-eating following these specific obesity treatments (BWL plus orlistat/placebo), BED was a negative prognostic indicator for some outcome variables.
doi:10.1016/j.brat.2013.01.002
PMCID: PMC3666334  PMID: 23376451
Binge eating disorder; Obesity; Behavioral weight loss; Medication; Latino; Hispanic
24.  The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study 
Purpose
Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome.
Methods
A total of 80 women were prospectively recruited to receive either metformin (n = 40) or orlistat (n = 40). Weight, BMI, waist, serum LH, total serum testosterone and lipid profile were assessed at baseline and after 3 months. The subjects’ ovulatory status was assessed after 3 months.
Results
There was no significant difference in ovulation between the two treatment groups (30% vs 15%). Treatment with either drug showed a significant decline in body weight, BMI (Body Mass Index), and waist circumference, but the degree of decline in both groups was the same. Patients who were treated with orlistat, showed a significant reduction in total testosterone and serum lipid. Women in metformin group showed a significant reduction in serum LH.
Conclusions
Both metformin and orlistat showed a similar effect on weight loss and ovulation rates.
doi:10.1007/s10815-011-9564-2
PMCID: PMC3162050  PMID: 21484319
Metformin; Orlistat; PCOS; Weight loss; Waist circumference
25.  Clinical and economic considerations of antiobesity treatment: a review of orlistat 
The objective of this study was to review the current knowledge about the use of orlistat from clinical and economic perspectives, and to assess this drug’s public health impact. Weight reduction by current antiobesity drugs, compared to placebo, is at most around 5 kg. Orlistat, the most studied antiobesity drug, is associated with the least-severe adverse effects, but compared with other drugs in its class it also delivers the most modest weight loss versus placebo (less than 3 kg). Orlistat appears to have a favorable risk/benefit profile, and cost-effectiveness ratios seem to be within a range that is generally considered acceptable. In the short-term, orlistat is related to reduced diabetes incidence and to slightly improved blood pressure and lipid profiles. Long-term clinical effects have been largely unstudied, however, and this study did not find reports that considered mortality as an endpoint. Given a very low continuation with orlistat treatment in the population and very modest and, apparently, only short-term clinical effects, orlistat is not likely to have a significant impact on the population health. Public health approaches of improving environmental and social factors to foster healthier food choices and increase physical activity remain essential for addressing the obesity epidemic.
PMCID: PMC3169961  PMID: 21935315
obesity; orlistat; weight loss; cost-effectiveness

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