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Effect of Polyglucosamine on Weight Loss and Metabolic Parameters in Overweight and Obesity: A Systemic Review and Meta-Analysis.
Perna, S, Basharat, SNM, Ali, KF, Eid, A, Gasparri, C, Infantino, V, Faliva, MA, Naso, M, Cazzola, R, Cestaro, B, et al
Nutrients. 2020;(8)
Abstract
The use of dietary supplements for weight loss has gained significant momentum. Polyglucosamine, a chitosan derivative, is a dietary supplement increasingly used for weight loss. In this meta-analysis, we systematically summarized and quantified the key findings of four randomized, placebo-controlled clinical trials examining the effects of polyglucosamine supplementation and caloric restriction, and physical activity on body weight, body mass index (BMI), and waist circumference in subjects with overweight and obesity. The control group was set with a physical activity from 6-7 MET-h/week activity and up to 21 MET-h/week activity with caloric restriction. Compliance in the latter trials was reported via a follow-up questionnaire with the individual participants. The analysis included 399 subjects followed for a period ranging from 12 weeks to one year. Subjects' age ranged from 21-75 years, BMI from 26-45 kg/m2, and all were white European or Caucasian in ethnicity. The meta-analyzed mean differences for random effects showed that polyglucosamine supplementation improves weight loss by -1.78 kg [-2.78, -0.79], BMI by -1.52 kg/m2 [-3.58, 0.54], and improves waist circumference reduction by -1.45 cm [-2.77, -0.12]. In conclusion, the use of polyglucosamine supplementation in conjunction with lifestyle behavioral therapies can be effective for weight reduction. Further studies are needed to examine the long-term effects of polyglucosamine supplementation on weight loss and other metabolic parameters.
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Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.
Avenell, A, Robertson, C, Skea, Z, Jacobsen, E, Boyers, D, Cooper, D, Aceves-Martins, M, Retat, L, Fraser, C, Aveyard, P, et al
Health technology assessment (Winchester, England). 2018;(68):1-246
Abstract
BACKGROUND Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. OBJECTIVES Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. DATA SOURCES Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). REVIEW METHODS Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. RESULTS A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. LIMITATIONS Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. CONCLUSIONS Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. FUTURE WORK Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. STUDY REGISTRATION This study is registered as PROSPERO CRD42016040190. FUNDING The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.
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Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly - A meta-analysis.
Solymár, M, Ivic, I, Pótó, L, Hegyi, P, Garami, A, Hartmann, P, Pétervári, E, Czopf, L, Hussain, A, Gyöngyi, Z, et al
PloS one. 2018;(11):e0207947
Abstract
BACKGROUND Metformin is the first-choice drug for patients with Type 2 diabetes, and this therapy is characterized by being weight neutral. However, in the elderly an additional unintentional weight loss could be considered as an adverse effect of the treatment. OBJECTIVES We aimed to perform a meta-analysis of placebo-controlled studies investigating the body weight changes upon metformin treatment in participants older than 60 years. MATERIALS AND METHODS PubMed, EMBASE and the Cochrane Library were searched. We included at least 12 week-long studies with placebo control where the mean age of the metformin-treated patients was 60 years or older and the body weight changes of the patients were reported. We registered our protocol on PROSPERO (CRD42017055287). RESULTS From the 971 articles identified by the search, 6 randomized placebo-controlled studies (RCTs) were included in the meta-analysis (n = 1541 participants). A raw difference of -2.23 kg (95% CI: -2.84 --1.62 kg) body weight change was detected in the metformin-treated groups as compared with that of the placebo groups (p<0.001). Both total cholesterol (-0.184 mmol/L, p<0.001) and LDL cholesterol levels (-0.182 mmol/L, p<0.001) decreased upon metformin-treatment. CONCLUSIONS Our meta-analysis of RCTs showed a small reduction of body weight together with slight improvement of the blood lipid profile in patients over 60 years. With regard to the risk of unintentional weight loss, metformin seems to be a safe agent in the population of over 60 years. Our results also suggest that metformin treatment may reduce the risk of major coronary events (-4-5%) and all-cause mortality (-2%) in elderly diabetic populations.
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Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
Aldekhail, NM, Logue, J, McLoone, P, Morrison, DS
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2015;(12):1071-80
Abstract
Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat in obese patients without diabetes, some studies suggest that patients who are obese and have diabetes mellitus lose more weight and have greater improvements in diabetic outcomes when treated with orlistat plus a lifestyle intervention than when treated by lifestyle interventions alone. The aim of this study was to review the evidence of the effects of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes. A systematic review of randomized controlled trials of orlistat in people with type 2 diabetes reporting diabetes outcomes in studies published between January 1990 and September 2013 was conducted. We searched for articles published in English in MEDLINE and EMBASE. Inclusion criteria included all randomized controlled trials of orlistat carried out on adult participants with a body mass index of 25 kg m(-2) or over diagnosed with type 2 diabetes, which reported weight change and at least one diabetic outcome. A total of 765 articles were identified out of which 12 fulfilled the inclusion criteria. The overall mean weight reduction (3, 6 and 12 months) in the orlistat group was -4.25 kg (95% CI: -4.5 to -3.9 kg). The mean weight difference between treatment and control groups was -2.10 kg (95% CI: -2.3 to -1.8 kg, P < 0.001), the mean HbA1c difference was -6.12 mmol mol(-1) (95% CI: -10.3 to -1.9 mmol mol(-1) , P < 0.004) and the mean fasting blood glucose difference was -1.16 mmol L(-1) (95% CI: -1.4 to -0.8 mmol L(-1) , P < 0.001). Treatment with orlistat plus lifestyle intervention resulted in significantly greater weight loss and improved glycaemic control in overweight and obese patients with type 2 diabetes compared with lifestyle intervention alone.
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Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials.
Johansson, K, Neovius, M, Hemmingsson, E
The American journal of clinical nutrition. 2014;(1):14-23
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Abstract
BACKGROUND Weight-loss maintenance remains a major challenge in obesity treatment. OBJECTIVE The objective was to evaluate the effects of anti-obesity drugs, diet, or exercise on weight-loss maintenance after an initial very-low-calorie diet (VLCD)/low-calorie diet (LCD) period (<1000 kcal/d). DESIGN We conducted a systematic review by using MEDLINE, the Cochrane Controlled Trial Register, and EMBASE from January 1981 to February 2013. We included randomized controlled trials that evaluated weight-loss maintenance strategies after a VLCD/LCD period. Two authors performed independent data extraction by using a predefined data template. All pooled analyses were based on random-effects models. RESULTS Twenty studies with a total of 27 intervention arms and 3017 participants were included with the following treatment categories: anti-obesity drugs (3 arms; n = 658), meal replacements (4 arms; n = 322), high-protein diets (6 arms; n = 865), dietary supplements (6 arms; n = 261), other diets (3 arms; n = 564), and exercise (5 arms; n = 347). During the VLCD/LCD period, the pooled mean weight change was -12.3 kg (median duration: 8 wk; range 3-16 wk). Compared with controls, anti-obesity drugs improved weight-loss maintenance by 3.5 kg [95% CI: 1.5, 5.5 kg; median duration: 18 mo (12-36 mo)], meal replacements by 3.9 kg [95% CI: 2.8, 5.0 kg; median duration: 12 mo (10-26 mo)], and high-protein diets by 1.5 kg [95% CI: 0.8, 2.1 kg; median duration: 5 mo (3-12 mo)]. Exercise [0.8 kg; 95% CI: -1.2, 2.8 kg; median duration: 10 mo (6-12 mo)] and dietary supplements [0.0 kg; 95% CI: -1.4, 1.4 kg; median duration: 3 mo (3-14 mo)] did not significantly improve weight-loss maintenance compared with control. CONCLUSION Anti-obesity drugs, meal replacements, and high-protein diets were associated with improved weight-loss maintenance after a VLCD/LCD period, whereas no significant improvements were seen for dietary supplements and exercise.
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Combination of very low energy diets and pharmacotherapy in the treatment of obesity: meta-analysis of published data.
Koutroumanidou, E, Pagonopoulou, O
Diabetes/metabolism research and reviews. 2014;(3):165-74
Abstract
Obesity has reached epidemic proportions globally, with more than 1 billion adults overweight - at least 300 million of them clinically obese - and is a major contributor to the global burden of chronic disease (heart disease and diabetes) and disability. The aim of the study was to perform a systematic review and meta-analysis of published data on the combination of very low energy diets also known as very low calorie diets and pharmacotherapy for its effectiveness in the treatment of obesity. A MEDLINE (Pubmed) search from 1970 to 2009 using multiple combinations of the relevant terms was carried out; the matching articles were also searched for additional references. Meta-analysis tools were used to summarize results. Only randomized controlled trials that compared pharmacotherapy with placebo after a very low energy diet period were selected, and six articles were finally considered to be appropriate for evaluation. The combination of very low energy diet and pharmacotherapy was found to be effective for people with obesity in clinical trials. The net effect of 6.1 kg placebo subtracted weight loss after 1 year represents a clinically meaningful result that is comparable with the effect of drugs given at the start of a weight loss programme. The present meta-analysis contributes to the understanding that combination therapies are expected to achieve greater weight loss than monotherapy; grasping this understanding, researcher has introduced newer anti-obesity pharmacological approaches have embraced combination therapies.
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Long-term effects of weight-reducing drugs in hypertensive patients.
Siebenhofer, A, Jeitler, K, Horvath, K, Berghold, A, Siering, U, Semlitsch, T
The Cochrane database of systematic reviews. 2013;(3):CD007654
Abstract
BACKGROUND All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option. PRIMARY OBJECTIVES To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause mortality - cardiovascular morbidity - adverse events SECONDARY OBJECTIVES - changes in systolic and/or diastolic blood pressure - body weight reduction even though sibutramine and rimonabant have been withdrawn from the market. SEARCH METHODS Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews (status as of 17(th) August, 2012). SELECTION CRITERIA Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo. DATA COLLECTION AND ANALYSIS Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity. MAIN RESULTS After the updated literature search, the number of studies remained the same, with eight studies comparing orlistat or sibutramine to placebo fulfilling our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg. AUTHORS' CONCLUSIONS In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being.
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Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments.
Das, C, Mendez, G, Jagasia, S, Labbate, LA
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. 2012;(3):225-39
Abstract
BACKGROUND Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity. METHODS We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions. RESULTS Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls. CONCLUSIONS Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.
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Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials.
Vilsbøll, T, Christensen, M, Junker, AE, Knop, FK, Gluud, LL
BMJ (Clinical research ed.). 2012;:d7771
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Abstract
OBJECTIVE To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus. DESIGN Systematic review with meta-analyses. DATA SOURCES Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011). Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin. DATA EXTRACTION Three authors independently extracted data. We used random effects models for the primary meta-analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors. RESULTS 25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference -2.9 kg, 95% confidence interval -3.6 to -2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (-3.2 kg, -4.3 to -2.1; three trials) as well as patients with diabetes (-2.8 kg, -3.4 to -2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia. CONCLUSIONS The present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.
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An integrated analysis of liver safety data from orlistat clinical trials.
Morris, M, Lane, P, Lee, K, Parks, D
Obesity facts. 2012;(4):485-94
Abstract
OBJECTIVE Orlistat is an oral gastrointestinal lipase inhibitor and is indicated for treatment of obesity in combination with a hypocaloric diet. Post-marketing reports of adverse reactions revealed hints for possible drug-induced liver injury which has prompted changes to the product information. Orlistat's development program, involving over 30,000 patients, did not indicate a hepatic safety issue. METHODS We analyzed liver function test data from randomized clinical trials of orlistat, using i) meta-analysis of published study safety data, ii) time-to-event analysis for individual patients, and iii) a novel and more sensitive method derived from the U.S. Food and Drug Administration's (FDA) evaluation of drug-induced serious hepatotoxicity (eDISH) technique. Over 10,000 subjects were included. RESULTS The combined odds ratio from a simple summary-level fixed-effects meta-analysis of treatment-emergent abnormalities in serum alanine aminotransferase (ALT) (defined as greater than the upper level of normal for 2 successive measurements) was 1.09 (95% CI 0.93-1.28), and in total bilirubin 1.24 (95% CI 1.03-1.49). Part of the small apparent effect was due to longer exposure to orlistat than to placebo, on average. A patient-level display, adjusting for regression towards the mean, and Kaplan-Meier analysis of changes in ALT and bilirubin, taking account of different exposure, showed no significant difference between orlistat and placebo. This shows that there is no signal for hepatic damage in clinical studies of orlistat. CONCLUSION While idiosyncratic liver injury following exposure to orlistat cannot be excluded, it is likely to be extremely rare.