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1.
Obes Rev ; 22(11): e13326, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34423889

RESUMO

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/m2 ). 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.


Assuntos
Fármacos Antiobesidade , Medicina Estatal , Adulto , Fármacos Antiobesidade/uso terapêutico , Humanos , Orlistate , Fentermina , Perda de Peso
2.
Int J Clin Pharmacol Ther ; 59(8): 539-548, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34236303

RESUMO

OBJECTIVE: Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. MATERIALS AND METHODS: In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. RESULTS: 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. CONCLUSION: 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.


Assuntos
Fármacos Antiobesidade , Depressores do Apetite , Adulto , Fármacos Antiobesidade/efeitos adversos , Humanos , México , Obesidade/tratamento farmacológico , Fentermina/efeitos adversos , Estudos Prospectivos
4.
J Clin Endocrinol Metab ; 106(10): 3019-3033, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34097062

RESUMO

CONTEXT: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. METHODS: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. RESULTS: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. CONCLUSION: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.


Assuntos
Compostos Benzidrílicos/administração & dosagem , Exenatida/administração & dosagem , Glucosídeos/administração & dosagem , Obesidade/tratamento farmacológico , Fentermina/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Topiramato/administração & dosagem , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Pessoa de Meia-Idade , Obesidade/complicações , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos , Adulto Jovem
6.
Obesity (Silver Spring) ; 29(6): 985-994, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33864346

RESUMO

OBJECTIVE: The study objective was to examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight or obesity by meta-analysis and systematic review. METHODS: Medical Subject Headings and free-text terms were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase up to April 18, 2020. The quality of randomized controlled trials was evaluated by the Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models. RESULTS: Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was related to the dose of phentermine/topiramate. Compared with placebo, the average weight loss was 3.55 kg (95% CI: 2.22-4.88) for 3.75/23 mg, 7.27 kg (95% CI: 6.40-8.13) for 7.5/46 mg, and 8.25 kg (95% CI: 6.92-9.79) for 15/92 mg. For phentermine/topiramate participants in different weight-loss subgroups, the weight loss of participants with ≥5%, ≥10%, and ≥15% baseline weight loss was 3.18 (95% CI: 2.75-3.67), 5.32 (95% CI: 4.53-6.25), and 5.65 (95% CI: 3.55-9.01), respectively. Compared with placebo, the adverse events associated with the treatment mainly included dysgeusia (odds ratio [OR] = 8.86, 95% CI: 5.65-13.89), paresthesia (OR = 8.51, 95% CI: 6.20-11.67), dry mouth (OR = 6.71, 95% CI: 5.03-8.94), disturbance in attention (OR = 4.48, 95% CI: 2.39-8.41), irritability (OR = 4.10, 95% CI: 2.29-7.33), hypoesthesia (OR = 3.81, 95% CI: 1.32-11.00), constipation (OR = 2.43, 95% CI: 2.02-2.93), and dizziness (OR = 2.26, 95% CI: 1.72-2.98). Phentermine/topiramate also reduced waist circumference, blood pressure, blood sugar levels, and lipid levels. CONCLUSIONS: Phentermine/topiramate has considerable benefit in reducing body weight, and the efficacy was closely related to the dosage. However, it increased the risk of nervous system-related adverse events.


Assuntos
Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Fentermina , Topiramato , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frutose/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/fisiopatologia , Sobrepeso/epidemiologia , Sobrepeso/fisiopatologia , Fentermina/administração & dosagem , Fentermina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Topiramato/administração & dosagem , Topiramato/efeitos adversos , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
7.
Diabetes Obes Metab ; 23(8): 1733-1745, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33904629

RESUMO

Obesity is highly prevalent worldwide, including among people with chronic kidney disease (CKD). The presence of severe and/or end-stage kidney disease complicates the treatment of obesity for several reasons, including restrictions on protein and fluid intake and renal excretion of several medications indicated for the treatment of obesity. The aim of this review is to assess the safety of intensive obesity treatments, such as very-low-energy diets (VLEDs), obesity pharmacotherapy and/or bariatric surgery, in people with end-stage kidney disease. A literature search was conducted to identify studies reporting safety outcomes for VLEDs, liraglutide, phentermine, phentermine-topiramate, naltrexone-bupropion and bariatric surgery in people with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2 or on dialysis. Limited data were insufficient to recommend VLEDs but highlighted their potential efficacy and the need for close clinical and biochemical monitoring. There were no data regarding centrally acting obesity pharmacotherapy in this population, although some glucagon-like peptide-1 analogues appear to safely induce weight loss at doses used for the treatment of type 2 diabetes. Some studies suggest an increased rate of complications of bariatric surgery in individuals with severe or end-stage CKD. Further prospective evaluation of intensive obesity management in the growing population with obesity and severe, end-stage and dialysis-dependent CKD is required.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Obesidade/complicações , Fentermina , Insuficiência Renal Crônica/complicações , Perda de Peso
8.
Diabetes Obes Metab ; 23(7): 1542-1551, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33651454

RESUMO

AIM: To assess the trends in the prescribing of antiobesity medications and the characteristics of patients recently initiating antiobesity drugs. MATERIALS AND METHODS: We conducted a population-based cohort study using claims data from commercial health insurances in the United States. Patients initiating an antiobesity drug between January 2004 and December 2018 were included. Trends in the utilization of antiobesity medications were plotted by year, as a proportion of any antiobesity treatment, and as initiation rates per 100 000. Descriptive statistics were used to summarize the characteristics of antiobesity initiators. RESULTS: From 2004 to 2018, 626 216 patients started an antiobesity medication (two per 100 000). Phentermine was the most frequently prescribed (50% in 2018). In recent years (2015-2018), among 227 692 patients who initiated an antiobesity drug, 51% started phentermine, 19% naltrexone-bupropion, and 13% liraglutide 3.0 mg. Compared to other agents, the use of liraglutide 3.0 mg increased between 2015 and 2018. The average age of initiators was 45 years, 81% of initiators were female, 32% had hypertension, 25% had dyslipidaemia, and 6% had type 2 diabetes. Time on treatment was generally short (mean 81 days). CONCLUSION: The overall use of antiobesity medications remained low over the past 15 years and phentermine was the preferred antiobesity agent. Although the use of potentially safer antiobesity agents, for example, liraglutide 3.0 mg, has increased in recent years, phentermine remained the most frequently prescribed agent among middle-aged adults with a moderate burden of comorbidities.


Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Adulto , Fármacos Antiobesidade/uso terapêutico , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Fentermina/uso terapêutico , Estados Unidos/epidemiologia
9.
Postgrad Med ; 133(4): 454-457, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33686912

RESUMO

Case: A 34-year-old woman with no significant past medical history presented to the hospital with sudden onset of palpitations with associated dyspnea and chest discomfort. She denied any similar previous episodes. Initial electrocardiogram (EKG) was consistent with a short R-P interval supraventricular tachycardia (SVT). Her transthoracic echocardiogram (TTE) revealed no structural abnormalities, TSH levels were normal, and urine drug screen was negative for any recreational drugs. However, the patient had been taking phentermine for weight loss.Discussion: The exact mechanism is not clear; however, we postulate that the sympathomimetic effects of phentermine likely contribute to SVT induction through enhanced AV nodal conduction or increased atrial ectopy. Conclusions: The only medication she was taking at home was phentermine, and the palpitations did not recur after discontinuation of the drug during follow-up. It is important to collect a thorough medication history when patients present with AV nodal reentrant tachycardia (AVNRT) or other SVT.


Assuntos
Fentermina/efeitos adversos , Taquicardia Supraventricular/induzido quimicamente , Adulto , Eletrocardiografia , Feminino , Humanos
10.
Cochrane Database Syst Rev ; 1: CD007654, 2021 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-33454957

RESUMO

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.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Depressores do Apetite/efeitos adversos , Hipertensão/tratamento farmacológico , Adulto , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Viés , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Dieta Redutora , Combinação de Medicamentos , Feminino , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Hipertensão/mortalidade , Lactonas/efeitos adversos , Lactonas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Orlistate/efeitos adversos , Orlistate/uso terapêutico , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Retirada de Medicamento Baseada em Segurança , Tempo , Topiramato/efeitos adversos , Topiramato/uso terapêutico
11.
Curr Obes Rep ; 10(1): 14-30, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410104

RESUMO

PURPOSE OF REVIEW: As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism. RECENT FINDINGS: Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Animais , Benzazepinas/uso terapêutico , Bupropiona/uso terapêutico , Humanos , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Orlistate/uso terapêutico , Sobrepeso/tratamento farmacológico , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Estados Unidos , United States Food and Drug Administration
12.
Curr Obes Rep ; 10(2): 81-89, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33492629

RESUMO

PURPOSE OF REVIEW: Weight regain after bariatric surgery is unfortunately a common occurrence. In this article, we have reviewed the data addressing this clinical problem focusing on pharmacological management of weight regain. RECENT FINDINGS: Data from several small, non-randomized, retrospective, and prospective studies provide evidence that a number of pharmacological options, both FDA approved and off-label, are effective in mitigating and managing weight regain after bariatric surgery. There is a suggestion that the optimal time to initiate weight loss medications may be at the time of weight plateau, rather than after weight regain. Adjuvant pharmacotherapy can help treat weight regain after bariatric surgery. Future studies should investigate the optimal timing for starting weight loss medications, as well as the best medication or combinations of medicines, for managing postoperative weight regain in different patient groups, including those who have undergone different types of bariatric surgeries.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Perda de Peso/efeitos dos fármacos , Humanos , Liraglutida/uso terapêutico , Obesidade/prevenção & controle , Obesidade/cirurgia , Fentermina/uso terapêutico , Período Pós-Operatório , Topiramato/uso terapêutico , Ganho de Peso/efeitos dos fármacos
13.
Drug Alcohol Depend ; 218: 108413, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33290875

RESUMO

RATIONALE: Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available. OBJECTIVES: The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder. METHODS: Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition. RESULTS: The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine. CONCLUSIONS: The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/administração & dosagem , Fentermina/uso terapêutico , Autoadministração , Topiramato/uso terapêutico , Adulto , Combinação de Medicamentos , Feminino , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
FP Essent ; 492: 25-29, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32383845

RESUMO

Pharmacotherapy, adjunctively with lifestyle interventions, is an option for any patient diagnosed with obesity (ie, body mass index [BMI] of 30 kg/m2 or greater) or with a BMI of 27 kg/m2 or greater and at least one coexisting condition, including type 2 diabetes, hypertension, hyperlipidemia, and sleep apnea. If the appropriate criteria are met, pharmacotherapy should be initiated for patients with overweight or obesity if lifestyle modification does not produce adequate weight loss. Lifestyle modifications should be continued and emphasized throughout treatment because it has been shown that adjunctive pharmacotherapy produces greater weight loss and weight loss maintenance than lifestyle interventions alone. Currently, five drugs are approved for weight management in adults: phentermine, orlistat, phentermine-topiramate, bupropion-naltrexone, and liraglutide. Certain drugs are approved for short-term management while others are approved for long-term management. Drug therapy should be customized to the individual patient, depending on needs, contraindications, and cost. Benefits of these drugs should be assessed regularly and a different drug should be considered if at least 5% of body weight is not lost by 3 months of therapy.


Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Obesidade , Adulto , Fármacos Antiobesidade/uso terapêutico , Benzazepinas , Diabetes Mellitus Tipo 2/complicações , Humanos , Obesidade/complicações , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico
17.
Obesity (Silver Spring) ; 28(6): 1023-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441476

RESUMO

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Derivação Gástrica/métodos , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Ganho de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/farmacologia , Período Pós-Operatório , Estudos Retrospectivos , Topiramato/farmacologia
19.
J Obes ; 2020: 8026016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318289

RESUMO

Background: Commercial weight loss programs provide valuable consumer options for those desiring support. Several commercial programs are reported to produce ≥3-fold greater weight loss than self-directed dieting. The effectiveness of JumpstartMD, a commercial pay-as-you-go program that emphasizes a low-to-very-low-carbohydrate real-food diet and optional pharmacologic treatment without prepackaged meals or meal replacement, has not previously been described. Methods: Completer and last observation carried forward (LOCF) of clinic-measured weight loss (kg) in 18,769 female and 3638 male JumpstartMD participants. Results: Completers lost (mean ± SE) 8.7 ± 0.04 kg, 9.5 ± 0.04% with 44.5 ± 0.5% achieving ≥10% weight loss at 3 months (mo, N = 14,999 completers); 11.8 ± 0.1 kg, 12.6 ± 0.1% with 66.4 ± 0.6% achieving ≥10% weight loss at 6 mo (N = 11,805); and 11.5 ± 0.2 kg, 12.0 ± 0.2% with 57.6 ± 0.9% achieving ≥10% weight loss at 12 mo (N = 8514). LOCF estimates were -6.5 ± 0.03 kg, -7.2 ± 0.03% with 27.1 ± 0.3% achieving ≥10% weight loss at 3 mo; -7.7 ± 0.04 kg, -8.5 ± 0.04% with 36.3 ± 0.3% achieving ≥10% weight loss at 6 mo; and -7.7 ± 0.1 kg, -8.4 ± 0.1% with 34.6 ± 0.3% achieving ≥10% weight loss after 12 mo. Frequent health coach meetings was a major determinant of weight loss, with women and men attending ≥75% of their weekly appointments losing 8.8 ± 0.04 and 11.9 ± 0.1 kg, respectively, after 3 mo, 13.1 ± 0.1 and 16.5 ± 0.3 kg after 6 mo, and 16.5 ± 0.3 and 19.4 ± 0.8 kg after 12 mo. Phentermine and phendimetrazine had a minor effect in women only at 1 (6.1% greater weight loss than untreated), 2 (4.1%), and 3 mo (1.2%), but treated patients showed longer enrollment than nontreated during the first 3 (females: +0.4 ± 0.01; males: +0.3 ± 0.04 mo), 6 (females: +1.1 ± 0.04; males: +1.0 ± 0.1 mo), and 12 mo (females: +2.7 ± 0.1; males: +2.4 ± 0.2 mo). JumpstartMD produced generally greater weight loss than published reports for other real-food and prepackaged-meal commercial programs and somewhat greater or comparable losses to meal replacement diets. Conclusion: A one-on-one medically supervised program that emphasized real low-carbohydrate foods produced effective weight loss, particularly in those attending ≥75% of their weekly appointments.


Assuntos
Obesidade/prevenção & controle , Adulto , Idoso , Dieta Redutora , Carboidratos da Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/administração & dosagem , Resultado do Tratamento , Perda de Peso , Programas de Redução de Peso
20.
Int J Obes (Lond) ; 44(5): 1021-1027, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32152496

RESUMO

AIMS: Over the past several decades, many antiobesity drugs have been withdrawn from the market due to unanticipated adverse events, often involving cardiotoxicity. This study aimed to evaluate the presence of cardiovascular safety signals with currently marketed antiobesity drugs. METHODS: We used the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and retrieved data from January 2013 through December 2018. We performed disproportionality analyses to detect cardiovascular safety signals with three antiobesity drugs recently approved for marketing: lorcaserin, naltrexone-bupropion, phentermine, and phentermine-topiramate. Three main cardiovascular outcomes were evaluated: valvular disorders, and pulmonary hypertension (PH) and other cardiovascular events (myocardial infarction, stroke, cardiovascular death, cardiac failure, and arrhythmia). RESULTS: During the evaluated period, a total of 6,787,840 adverse event reports were submitted to FAERS. Of these, 2687 involved lorcaserin, 3960 involved phentermine/phentermine-topiramate, and 2873 involved naltrexone-bupropion. Lorcaserin was associated with a significantly greater proportion of reports of valvular disorders (ROR = 4.39; 95% CI 2.72-5.07). None of the antiobesity drugs were associated with a safety signal for valvulopathy, PH, or other cardiovascular events. CONCLUSIONS: Our analyses revealed a signal for valvular disorders with lorcaserin and did not detect a safety signal for other cardiovascular events with recently approved antiobesity drugs. Further research is needed to explore and validate this signal.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Doenças Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Fármacos Antiobesidade/uso terapêutico , Benzazepinas/efeitos adversos , Benzazepinas/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Obesidade/tratamento farmacológico , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Estados Unidos , United States Food and Drug Administration
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