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Nutricion Hospitalaria Sep 2013The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes,... (Review)
Review
The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is orlistat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks). The Food and Drug Administration (FDA) has recently approved lorcaserin and the combination phentermine/ topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future.
Topics: Anti-Obesity Agents; Drug Approval; Drug Therapy, Combination; Humans; Obesity; Risk Assessment; United States; United States Food and Drug Administration
PubMed: 24010752
DOI: 10.3305/nh.2013.28.sup5.6927 -
Therapeutic Advances in Drug Safety Aug 2013Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore...
Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn. Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves. Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of significant psychiatric adverse effects. Orlistat was approved in Europe and the United States for long-term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects. Phentermine and diethylpropion can only be used for less than 12 weeks because the long-term safety of these drugs is unknown. Ephedrine and caffeine are natural substances but the effects on weight reduction are modest. As a result there is a huge unmet need for effective and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long-term safety data are lacking.
PubMed: 25114779
DOI: 10.1177/2042098613489721 -
Clinics (Sao Paulo, Brazil) May 2017The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.
Topics: Appetite Depressants; Diethylpropion; Humans; Mazindol; Obesity; Overweight; Publication Bias; Reproducibility of Results; Risk Factors; Treatment Outcome; Weight Loss
PubMed: 28591345
DOI: 10.6061/clinics/2017(05)10 -
Substance Abuse and Rehabilitation 2014Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They... (Review)
Review
Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.
PubMed: 24966713
DOI: 10.2147/SAR.S37257 -
Annals of Internal Medicine Apr 2005In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used. (Meta-Analysis)
Meta-Analysis
BACKGROUND
In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used.
PURPOSE
To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss.
DATA SOURCES
Electronic databases, experts in the field, and unpublished information.
STUDY SELECTION
Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively.
DATA EXTRACTION
The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication.
DATA SYNTHESIS
All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, -1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported.
LIMITATIONS
Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses.
CONCLUSIONS
Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.
Topics: Adult; Anti-Obesity Agents; Humans; Obesity; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 15809465
DOI: 10.7326/0003-4819-142-7-200504050-00012 -
MSMR Jan 2024The U.S. military has witnessed rising obesity among active component service members. The Department of Defense authorized coverage of weight loss medications in 2018,...
The U.S. military has witnessed rising obesity among active component service members. The Department of Defense authorized coverage of weight loss medications in 2018, but no study has evaluated prescription prevalence within the active component. This descriptive retrospective cohort study analyzed data from active component U.S. military service members from January 2018 through June 2023. The study used data from the Defense Medical Surveillance System to determine prescription period prevalence of weight loss medication. Data on demographics, body mass index, and history of diabetes were considered. The study revealed a 100-fold increase in the prescription period prevalence of weight loss agents in the active component from their initial authorization date. Demographics associated with higher prescription period prevalence were non-Hispanic Black race and ethnicity, female sex, and older age. Service members in the health care occupations and the Navy had higher prevalence compared to other service branches and occupations. The findings indicate a significant rise in the period prevalence of weight loss prescriptions over time. Further research is recommended to assess the effectiveness, safety, and use in austere military environments.
Topics: Female; Humans; United States; Prevalence; Retrospective Studies; Military Personnel; Anti-Obesity Agents; Weight Loss
PubMed: 38359359
DOI: No ID Found -
British Medical Journal Apr 1968
Clinical Trial
Topics: Appetite Depressants; Diet, Reducing; Diethylpropion; Fenfluramine; Fluorine; Humans; Phenethylamines; Sleep
PubMed: 5641992
DOI: 10.1136/bmj.2.5598.175-b -
International Journal of Obesity (2005) Mar 2018Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care...
OBJECTIVE
Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care Act (ACA) enacted in 2010 included provisions for private and public health insurance plans that expanded coverage for lifestyle/behavior modification and bariatric surgery for the treatment of obesity. Pharmacotherapy, however, has not been included despite their evidence-based efficacy. We set out to investigate the coverage of Food and Drug Administration-approved medications for obesity within Medicare, Medicaid and ACA-established marketplace health insurance plans.
METHODS
We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states.
RESULTS
Among 136 marketplace health insurance plans, 11% had some coverage for the specified drugs in only nine states. Medicare policy strictly excludes drug therapy for obesity. Only seven state Medicaid programs have drug coverage.
CONCLUSIONS
Obesity requires an integrated approach to combat its public health threat. Broader coverage of pharmacotherapy can make a significant contribution to fighting this complex and chronic disease.
Topics: Anti-Obesity Agents; Humans; Medicaid; Medicare; Obesity; Patient Protection and Affordable Care Act; Prescriptions; United States
PubMed: 29151591
DOI: 10.1038/ijo.2017.287 -
Australian Family Physician Aug 2006Obesity is a chronic disease requiring a similar long term approach to management as that of other chronic conditions. (Review)
Review
BACKGROUND
Obesity is a chronic disease requiring a similar long term approach to management as that of other chronic conditions.
OBJECTIVE
This article discusses the role of medications in the overall management of obesity.
DISCUSSION
Management needs to be multifaceted, aiming to alter the patient and family micro-environment to one favouring better weight control through sustainable behavioural changes to physical activity and diet. Weight loss medications may provide additional benefit. Currently we have only two medications suitable for long term therapy--orlistat and sibutramine. Sibutramine, which acts centrally to suppress appetite, has shown efficacy for up to 2 years. Orlistat, a lipase inhibitor, reduces fat absorption and has been shown to reduce and maintain weight for up to 4 years. The effect of these medications is modest, generally providing less than 5 kg weight loss when compared with placebo. Patients need to have realistic expectations and understand the benefits of sustained modest weight loss. It is important that weight loss medications are prescribed in combination with lifestyle modification.
Topics: Anti-Obesity Agents; Chronic Disease; Cyclobutanes; Diethylpropion; Humans; Lactones; Obesity; Orlistat; Phentermine; Weight Loss
PubMed: 16894428
DOI: No ID Found -
Brazilian Journal of Medical and... Dec 1999The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol...
The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol (EtOH) and diethylpropion (DEP) we examined the locomotion-activating effects of these drugs given alone or in combination in mice. We also determined whether this response was affected by dopamine (DA) or opioid receptor antagonists. A total of 160 male Swiss mice weighing approximately 30 g were divided into groups of 8 animals per group. The animals were treated daily for 7 consecutive days with combined EtOH + DEP (1.2 g/kg and 5.0 mg/kg, ip), EtOH (1.2 g/kg, ip), DEP (5.0 mg/kg, ip) or the control solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/kg, ip), the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip), or vehicle. On days 1, 7 and 10 after the injections, mice were assessed in activity cages at different times (15, 30, 45 and 60 min) for 5 min. The acute combination of EtOH plus DEP induced a significantly higher increase in locomotor activity (day 1: 369.5 +/- 34.41) when compared to either drug alone (day 1: EtOH = 232.5 +/- 23.79 and DEP = 276.0 +/- 12.85) and to control solution (day 1: 153.12 +/- 7.64). However, the repeated administration of EtOH (day 7: 314.63 +/- 26.79 and day 10: 257.62 +/- 29.91) or DEP (day 7: 309.5 +/- 31.65 and day 10: 321.12 +/- 39. 24) alone or in combination (day 7: 459.75 +/- 41.28 and day 10: 427. 87 +/- 33.0) failed to induce a progressive increase in the locomotor response. These data demonstrate greater locomotion-activating effects of the EtOH + DEP combination, probably involving DA and/or opioid receptor stimulation, since the daily pretreatment with HAL (day 1: EtOH + DEP = 395.62 +/- 11.92 and EtOH + DEP + HAL = 371.5 +/- 6.76; day 7: EtOH + DEP = 502.5 +/- 42.27 and EtOH + DEP + HAL = 281.12 +/- 16.08; day 10: EtOH + DEP = 445.75 +/- 16.64 and EtOH + DEP + HAL = 376.75 +/- 16.4) and NAL (day 1: EtOH + DEP = 553.62 +/- 38.15 and EtOH + DEP + NAL = 445.12 +/- 55.67; day 7: EtOH + DEP = 617.5 +/- 38.89 and EtOH + DEP + NAL = 418.25 +/- 61.18; day 10: EtOH + DEP = 541.37 +/- 32.86 and EtOH + DEP + NAL = 427.12 +/- 51.6) reduced the locomotor response induced by combined administration of EtOH + DEP. These findings also suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by the combination.
Topics: Animals; Appetite Depressants; Central Nervous System Depressants; Diethylpropion; Dopamine Antagonists; Drug Interactions; Ethanol; Haloperidol; Male; Mice; Motor Activity; Naloxone; Narcotic Antagonists
PubMed: 10585638
DOI: 10.1590/S0100-879X1999001200015