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JAMA Jun 2016Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.
OBJECTIVE
To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.
STUDY SELECTION
Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.
MAIN OUTCOMES AND MEASURES
Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.
RESULTS
Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE
Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.
Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss
PubMed: 27299618
DOI: 10.1001/jama.2016.7602 -
Obesity Reviews : An Official Journal... Nov 2021Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice.... (Review)
Review
Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI ≥ 27 kg/m ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.
Topics: Adult; Anti-Obesity Agents; Humans; Orlistat; Phentermine; State Medicine; Weight Loss
PubMed: 34423889
DOI: 10.1111/obr.13326 -
The Cochrane Database of Systematic... Jan 2021This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.
OBJECTIVES
Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.
SELECTION CRITERIA
Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.
MAIN RESULTS
This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.
AUTHORS' CONCLUSIONS
In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Bias; Blood Pressure; Body Weight; Bupropion; Diet, Reducing; Drug Combinations; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Naltrexone; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Time; Topiramate
PubMed: 33454957
DOI: 10.1002/14651858.CD007654.pub5 -
Gastroenterology Apr 2018We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults.
METHODS
We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration-approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, -4.4 to -3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, -3.5 to -3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors.
CONCLUSIONS
In a systematic review and network meta-analysis, we found Food and Drug Administration-approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications.
PROSPERO
CRD42016039486.
Topics: Adult; Anti-Obesity Agents; Biomarkers; Blood Glucose; Blood Pressure; Female; Glycated Hemoglobin; Humans; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Protective Factors; Risk Assessment; Risk Factors; Treatment Outcome; Waist Circumference; Weight Loss
PubMed: 29305933
DOI: 10.1053/j.gastro.2017.12.024 -
Diabetology & Metabolic Syndrome Oct 2021Obesity is a complex disease with an increasing prevalence worldwide. There are different weight-management options for obesity treatment, including dietary control,...
BACKGROUND
Obesity is a complex disease with an increasing prevalence worldwide. There are different weight-management options for obesity treatment, including dietary control, exercise, surgery, and medication. Medications are always associated with different responses from different people. More safety and efficacy of drugs with fewer side effects are valuable for any clinical condition. In this systematic review and network meta-analysis, different anti-obesity drugs are compared to identify the most effective drug.
METHODS
All relevant studies were extracted by searching national and international databases of SID, MagIran, ProQuest, PubMed, Science Direct, Scopus, Web of Science (WoS), and Google Scholar without time limit until October 2020. Finally, the meta-analysis was performed with the 11 remaining studies containing 14 different drug supplements. The standardized mean difference (SMD) was calculated at a 95% confidence interval (CI) to evaluate the effects of each treatment group compared with placebo. A random-effect model was used to evaluate the effect of individual studies on the final result. Heterogeneity and incompatibility of the network were assessed by Cochran's Q and Higgins I, and the Net Heat chart, respectively. Data analysis was performed using R software.
RESULTS
Our results showed that there were significant mean effects in people intervened with Phentermine 15.0 mg + Topiramate 92.0 mg, Phentermine 7.5 mg + Topiramate 46.0 mg, Pramlintide, Naltrexone + Bupropion 32, and Liraglutide, with SMD effects size = - 9.1, - 7.4, - 6.5, - 5.9, - 5.35, respectively.
CONCLUSION
This study was performed to compare the effect of different drugs used for weight loss in obese patients. The most effective drugs for weight loss were phentermine and topiramate, pramlintide, naltrexone, bupropion, and liraglutide compared to placebo treatment, respectively. This study provides new insights into anti-obesity drugs and hopes to shed new light on future research to manage and treat obesity.
PubMed: 34663429
DOI: 10.1186/s13098-021-00733-5 -
Frontiers in Endocrinology 2020Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there...
Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there are limited strategies specifically targeting NAFLD. This systematic review summarizes the existing literature on hepatic effects of medications used for weight loss. Glucagon-like peptide 1 (GLP-1) agonists are the best-studied in this regard, and evidence consistently demonstrates reduction in liver fat content, sometimes accompanied by improvements in histological features of steatohepatitis and reductions in serum markers of hepatic injury such as alanine aminotransferase (ALT). It remains unclear whether these benefits are independent of the weight loss caused by these agents. Literature is limited regarding effects of orlistat, but a small number of reports suggest that orlistat reduces liver fat content and improves histologic features of NASH, benefits which may also be driven primarily by weight loss. A sizeable body of literature on hepatic effects of metformin yields mixed results, with a probability of modest benefit, but no consistent signal for strong benefit. There are insufficient data on hepatic effects of topiramate, phentermine, naltrexone, bupropion, and lorcaserin. Finally, a few studies to date suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitors may reduce liver fat content and cause modest reductions in ALT, but further study is needed to better characterize these effects. Based on available data, GLP-1 agonists have the strongest evidence base demonstrating beneficial effects on NAFLD, but it is not clear if any weight loss medication has effects on NAFLD superior to those of nutritional modification and exercise alone.
Topics: Anti-Obesity Agents; Fatty Liver; Humans; Non-alcoholic Fatty Liver Disease; Prognosis; Weight Loss
PubMed: 32153507
DOI: 10.3389/fendo.2020.00070 -
Journal of Drug Assessment 2019To systematically review the literature on weight management pharmaceutical use in patients who have had bariatric surgery. Google Scholar, Pubmed, Cochrane, Embase,...
To systematically review the literature on weight management pharmaceutical use in patients who have had bariatric surgery. Google Scholar, Pubmed, Cochrane, Embase, Web of Science, and Clinical Trials were searched from inception to December 31st, 2018 inclusive. Thirteen studies met inclusion and reported decreases in weight with the use of weight management medications in post-bariatric surgical patients. Five studies examined weight loss outcomes by the type of bariatric surgery procedure, and four of these studies observed less weight loss in patients who had undergone gastric sleeve compared to those who had roux-en-y bypass ( = 3 papers) and adjustable gastric banding ( = 1 paper) with medication use. Four studies compared the effectiveness of medications for weight management and observed slightly greater weight loss with the use of topiramate and phentermine as a monotherapy compared to other weight loss medications. Using a sub-sample of participants, authors observed less weight loss on metformin but not phentermine or topiramate for younger adults. Another post-hoc analysis in the same sample observed greater weight loss for older adults with liraglutide 1.8 mg. Side effects were reported in seven studies and were overall consistent with those previously reported in non-surgical populations. Results of this systematic review suggest pharmacotherapy may be an effective tool as an adjunct to diet and physical activity to support weight loss in post-bariatric surgery patients. However, due to most studies lacking a control or placebo group, more rigorous research is required to determine the efficacy of this intervention.
PubMed: 33110683
DOI: 10.1080/21556660.2019.1678478