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1.
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 We contacted authors of relevant papers about further published and unpublished work.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(rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively.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
2.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
3.
Nutrients ; 11(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533291

RESUMO

The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.


Assuntos
Depressores do Apetite/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Obesidade/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Resposta de Saciedade/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/psicologia , Compostos Fitoquímicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
Clin Ther ; 41(9): 1798-1815, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31351676

RESUMO

PURPOSE: Obesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss. METHODS: PubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction for the database searches. We extracted and combined data from studies that reported adverse drug events and weight change. A random effects meta-analytic model was applied in all calculations. The Cochrane Collaboration tool was used to assess the quality and bias of all included studies. Quality of evidence was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. FINDINGS: Fifty-three studies were included, with a total of 16,903 patients with a median follow-up of 12 weeks (2-260 weeks). The appetite suppressants showed a significant weight loss compared with placebo (mean difference [MD], -4.70 kg; 95% CI, -5.25 to -4.15; I2 = 100%; 43 studies). There was an increased total number of adverse events, dry mouth, constipation, insomnia, dizziness, and tachycardia reported in the intervention group (risk ratio [RR], 1.06; 95% CI, 1.01 to 1.10; I2 = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I2 = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I2 = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I2 = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I2 = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I2 = 0% [10 studies], respectively). Sibutramine showed a significant increase in heart rate and mean diastolic pressure compared with placebo (MD, 4.17 beats/min [95% CI, 3.60 to 4.74; I2 = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I2 = 98%; 22 studies]). IMPLICATIONS: These drugs are effective for weight loss in overweight and obese patients; however, they increase the risk of adverse events. In fact, the evidence is of low quality, the data availability of studied agents (especially for cardiovascular outcomes) are limited, and the studies are of short duration. PROSPERO identifier: CRD42018091083.


Assuntos
Depressores do Apetite/efeitos adversos , Sistema Nervoso Central/efeitos dos fármacos , Adulto , Depressores do Apetite/uso terapêutico , Humanos , Sobrepeso/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Metabolism ; 96: 83-91, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30902750

RESUMO

BACKGROUND: This pilot study evaluated whether adding phentermine to liraglutide would induce further weight loss in participants who had previously lost weight with liraglutide alone. SUBJECTS/METHODS: Participants were 45 adults with obesity (75.6% female, 55.6% white, body mass index = 34.3 ±â€¯4.7 kg/m2) who had lost an average of 12.6 ±â€¯6.8% of initial weight during a prior 1-year randomized trial with liraglutide and intensive behavioral treatment. Participants were re-randomized, in a double-blinded fashion, to liraglutide 3.0 mg plus phentermine 15.0 mg (liraglutide-phentermine) or liraglutide plus placebo (liraglutide-placebo). Participants also were provided with four, 15-minute counseling sessions during the 12-week extension study. RESULTS: At week 12, the liraglutide-phentermine and liraglutide-placebo groups lost a mean (±SEM) of 1.6 ±â€¯0.6% and 0.1 ±â€¯0.5% of re-randomization weight, respectively (p = 0.073). Two (9.1%) liraglutide-phentermine participants and one (4.3%) liraglutide-placebo participant lost ≥5% of re-randomization weight; 19 (86.4%) and 16 (69.9%) participants, respectively, maintained their full weight loss achieved in the prior 1-year trial (p = 0.125). Liraglutide-phentermine participants generally reported larger reductions in hunger and food preoccupation than liraglutide-placebo participants during the first 8 weeks of the extension study. CONCLUSIONS: The combination of liraglutide and phentermine appeared to be well-tolerated but did not produce additional clinically meaningful weight loss in individuals who had already lost 12.6% of initial weight with liraglutide alone. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02911818.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Adulto , Idoso , Fármacos Antiobesidade/efeitos adversos , Apetite/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Fome/efeitos dos fármacos , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Fentermina/efeitos adversos , Projetos Piloto , Resultado do Tratamento , Perda de Peso
6.
Med Princ Pract ; 28(2): 167-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30517949

RESUMO

OBJECTIVES: Nutraceuticals are advertised and sold with the label claim of being natural and safe herbal products. Due to the absence of clear regulations and guidelines for safety assessments of these products, nutraceuticals are commonly adulterated in order to increase sales. The objective of the current study was to design a comprehensive evaluation system to assess the safety, efficacy, authenticity according to label claim, and pharmaceutical quality of herbal slimming products in between 2015 and 2017. METHODS: We designed a comprehensive assessment system to evaluate the safety, authenticity according to label claim, and pharmaceutical quality of slimming nutraceuticals. Six different popular products were evaluated (Zotreem Plus®, Zotreem Extra®, Malaysian Super Slim®, AB Slim®, Chinese Super Slim®, and Metabolites®). The pharmaceutical evaluation included analyzing the samples via high-performance liquid chromatography to determine any possible adulterants. Additionally, the products' physical properties were assessed via pharmacopeial tests. Finally, a microbial evaluation and a cross-sectional observational retrospective prevalence study were conducted to assess the products' safety and efficacy. -Results: The tested products were found to be adulterated with unreported active pharmaceutical ingredients such as sibutramine, sildenafil, phenolphthalein, and orlistat. Furthermore, they contained heterogeneous amounts of adulterants and exhibited an unsatisfactory pharmaceutical and microbial quality. Finally, the observational survey conducted on users showed that high percentages of participants suffered from common side effects such as depression, diarrhea, and hypertension. CONCLUSIONS: These products threaten the health of consumers. There is a need to raise awareness of the lethal consequences of illegal nutraceuticals.


Assuntos
Fármacos Antiobesidade/análise , Depressores do Apetite/análise , Suplementos Nutricionais/análise , Medicamentos de Ervas Chinesas/análise , Medicamentos sem Prescrição/análise , Fármacos Antiobesidade/efeitos adversos , Depressores do Apetite/efeitos adversos , Estudos Transversais , Suplementos Nutricionais/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Egito , Humanos , Medicamentos sem Prescrição/efeitos adversos , Perda de Peso
7.
Circulation ; 139(3): 366-375, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30586726

RESUMO

BACKGROUND: Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61). METHODS: CAMELLIA-TIMI 61 randomly assigned 12 000 overweight or obese patients with or at high risk for atherosclerotic CV disease to lorcaserin or placebo on a background of lifestyle modification. The primary renal outcome was a composite of new or worsening persistent micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death. RESULTS: At baseline, 23.8% of patients had an estimated glomerular filtration rate (eGFR) <60 mL·min-1·1.73 m-2 and 19.0% had albuminuria (urinary albumin:creatinine ratio ≥30 mg/g). Lorcaserin reduced the risk of the primary renal composite outcome (4.2% per year versus 4.9% per year; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=0.0064). The benefit was consistent across subpopulations at increased baseline CV and renal risk. Lorcaserin improved both eGFR and urinary albumin:creatinune ratio within the first year after randomization. The effect of lorcaserin on weight, hemoglobin A1c, and systolic blood pressure was consistent regardless of baseline renal function. Likewise, there was no excess in cardiovascular events in patients assigned to lorcaserin in comparison with placebo, regardless of renal function. After adjustment for baseline characteristics, those with evidence of kidney disease were at increased risk of major CV events. Compared with patients with an eGFR ≥90 mL·min-1·1.73 m-2, those with an eGFR 60-90 and those <60 mL·min-1·1.73 m-2 had HRs of 1.25 (95% CI, 1.01, 1.56) and 1.51 (95% CI, 1.17, 1.95), respectively ( P for trend 0.0015). Likewise, compared with patients with no albuminuria (<30 mg/g), those microalbuminuria and those with macroalbuminuria had HRs of 1.46 (95% CI, 1.22, 1.74) and 2.10 (95% CI, 1.58, 2.80), respectively ( P for trend <0.0001). CONCLUSIONS: Renal dysfunction was associated with increased CV risk in overweight and obese patients. When added to diet and lifestyle, lorcaserin reduced the rate of new-onset or progressive renal impairment in comparison with placebo. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02019264.


Assuntos
Depressores do Apetite/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Benzazepinas/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Nefropatias/epidemiologia , Rim/efeitos dos fármacos , Obesidade/tratamento farmacológico , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Depressores do Apetite/efeitos adversos , Benzazepinas/efeitos adversos , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Dieta Redutora , Progressão da Doença , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/mortalidade , Obesidade/fisiopatologia , Obesidade/psicologia , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Agonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
9.
Pharmacoepidemiol Drug Saf ; 28(3): 370-376, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29992679

RESUMO

BACKGROUND: Change-point analysis (CPA) is a powerful method to analyse pharmacovigilance data but it has never been used on the disproportionality metric. OBJECTIVES: To optimize signal detection investigating the interest of time-series analysis in pharmacovigilance and the benefits of combining CPA with the proportional reporting ratio (PRR). METHODS: We investigated the couple benfluorex and aortic valve incompetence (AVI) using the French National Pharmacovigilance and EudraVigilance databases: CPA was applied on monthly counts of reports and the lower bound of monthly computed PRR (PRR-). We stated a CPA hypothesis that the substance-event combination is more likely to be a signal when the 2 following criteria are fulfilled: PRR- is greater than 1 with at least 5 cases, and CPA method detects at least 2 successive change points of PRR- which made consecutively increasing segments. We tested this hypothesis by 95 test cases identified from a drug safety reference set and 2 validated signals from EudraVigilance database: CPA was applied on PRR-. RESULTS: For benfluorex and AVI, change points detected by CPA on PRR- were more meaningful compared with monthly counts of reports: More change points detected and detected earlier. In the reference set, 14 positive controls satisfied CPA hypothesis, 6 positive controls only met first requirements, 3 negative controls only met first requirement, and 2 validated signals satisfied CPA hypothesis. CONCLUSIONS: The combination of CPA and PRR represents a significant advantage in detecting earlier signals and reducing false-positive signals. This approach should be confirmed in further studies.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Farmacovigilância , Insuficiência da Valva Aórtica/induzido quimicamente , Insuficiência da Valva Aórtica/epidemiologia , Depressores do Apetite/efeitos adversos , Interpretação Estatística de Dados , Bases de Dados Factuais , Fenfluramina/efeitos adversos , Fenfluramina/análogos & derivados , França/epidemiologia , Humanos
10.
Curr Nutr Rep ; 7(4): 329-334, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30168043

RESUMO

PURPOSE OF REVIEW: Obesity is a life-limiting disease that is associated with a number of co-morbidities. Bariatric surgery remains the most efficacious and durable weight loss method available to patients. However, a significant percentage of patients can regain weight resulting in frustration, depression, and return of obesity-related co-morbidities. The present review provides an overview of the most common therapeutic modalities available to combat weigh regain after weight loss surgery. RECENT FINDINGS: Given the high percentage of patients with weight regain after surgery, significant effort has been placed on developing treatment options in the last few years. Tremendous work has taken place in the realm of cognitive behavior therapy, appetite suppressants, and endoscopic procedures with the hope of reducing the need for revision surgery which can be associated with significant complications. Weight regain is unfortunately a common phenomenon associated with all weight loss modalities including bariatric surgery. We now have a number of treatment options that can reverse the weight loss trend.


Assuntos
Depressores do Apetite/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Terapia Cognitivo-Comportamental/métodos , Endoscopia Gastrointestinal/métodos , Obesidade/cirurgia , Ganho de Peso/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Comportamento Alimentar/efeitos dos fármacos , Humanos , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/psicologia , Prevalência , Recidiva , Reoperação , Fatores de Risco , Resultado do Tratamento
12.
Drug Dev Res ; 79(5): 225-233, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30188585

RESUMO

Preclinical Research & Development Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose-dependent fashion in either nondeprived or 12 hr food-deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.


Assuntos
Depressores do Apetite/administração & dosagem , Dietilpropiona/administração & dosagem , Topiramato/administração & dosagem , Animais , Depressores do Apetite/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Dietilpropiona/efeitos adversos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Masculino , Leite , Ratos Wistar , Topiramato/efeitos adversos
13.
Ann Plast Surg ; 81(4): 503-507, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30204622

RESUMO

PURPOSE: Phentermine is the most prescribed antiobesity drug in America, with 2.43 million prescriptions written in 2011. Case reports suggest there are anesthetic risks, such as refractory hypotension, involved with its perioperative use. Despite these risks and the frequency of phentermine use among plastic surgery patients, there are no published guidelines for the perioperative management of phentermine use in the plastic surgery literature. To address this patient safety issue, we performed a systematic review and provide management recommendations. METHODS: A systematic review of the pharmacology of phentermine and the anesthetic risks involved with its perioperative use was undertaken using the search engines PubMed/MEDLINE, EMBASE, and Scopus. RESULTS: A total of 251 citations were reviewed, yielding 4 articles that discussed perioperative phentermine use and complications with anesthesia. One was a review article, 2 were case reports, and 1 was a letter. Complications included hypotension, hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and acute pulmonary edema. CONCLUSIONS: The relationship between phentermine and anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is the most reported complication of perioperative phentermine use. Specifically, phentermine-induced hypotension may be unresponsive to vasopressors that rely on catecholamine release, such as ephedrine. Therefore, the decision to perform surgery, especially elective surgery, in a patient taking phentermine should be made with caution. Because of the half-life of phentermine, we recommend discontinuing phentermine for at least 4 days prior to surgery. This differs from the classic 2-week discontinuation period recommended for "fen-phen." The patient should be made aware of the increased risk of surgery, and a skilled anesthesiologist should monitor intraoperative blood pressure and body temperature for signs of autonomic derailment.


Assuntos
Anestesia , Anestésicos/farmacologia , Depressores do Apetite/farmacologia , Fentermina/farmacologia , Procedimentos Cirúrgicos Reconstrutivos , Anestésicos/efeitos adversos , Depressores do Apetite/efeitos adversos , Interações Medicamentosas , Humanos , Fentermina/efeitos adversos
18.
Diabetes Obes Metab ; 20(8): 1836-1851, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29938884

RESUMO

AIM: We performed acute and chronic studies in healthy and diet-induced obese animals using mouse-specific or monkey-specific dual GLP-1R/GCGR agonists to investigate their effects on food intake, body weight, blood glucose control and insulin secretion. The selective GLP-1R agonist liraglutide was used as comparator. METHODS: The mouse-specific dual agonist and liraglutide were tested in lean wild type, GLP-1R knockout and diet-induced obese mice at different doses. A chronic study was performed in DIO mice to investigate the effect on body weight, food consumption and total energy expenditure (TEE) in obese and diabetic monkeys with a focus on body weight and energy intake. RESULTS: The mouse-specific dual agonist and liraglutide similarly affected glycaemic control. A higher loss in body weight was measured in dual agonist-treated obese mice. The dual agonist significantly enhanced plasma glucose excursion in overnight fed GLP-1R-/- mice, probably reflecting a potent GCGR agonist activity. It increased TEE and enhanced fat and carbohydrate oxidation, while liraglutide produced no effect on TEE. In obese and diabetic monkeys, treatment with the monkey-specific dual agonist reduced total energy intake to 60%-70% of baseline TEI during chronic treatment. A decrease in body weight and significant improvement in glucose tolerance was observed. CONCLUSIONS: In DIO mice and non-human primates, dual agonists elicited robust glycaemic control, similar to the marketed GLP-1R agonist, while eliciting greater effects on body weight. Results from DIO mice suggest that the increase in TEE is caused not only by increased fat oxidation but also by an increase in carbohydrate oxidation.


Assuntos
Depressores do Apetite/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Receptores de Glucagon/agonistas , Animais , Animais não Endogâmicos , Depressores do Apetite/administração & dosagem , Depressores do Apetite/efeitos adversos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Secreção de Insulina/efeitos dos fármacos , Macaca fascicularis , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/sangue , Obesidade/etiologia , Obesidade/metabolismo , Distribuição Aleatória , Receptores de Glucagon/metabolismo
19.
Nutrients ; 10(4)2018 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-29642492

RESUMO

Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which slow gastric emptying. Gastric emptying regulates postprandial blood glucose. Tryptophan has been reported to decrease energy intake. We investigated the effects of intragastric tryptophan on the glycaemic response to, and gastric emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese participants (n = 16 each) received intragastric infusions of 1.5 g ("Trp-1.5g") or 3.0 g ("Trp-3.0g") tryptophan, or control, and 15 min later consumed a mixed-nutrient drink (56 g carbohydrates). Gastric emptying (13C-acetate breath-test), blood glucose, plasma C-peptide, glucagon, cholecystokinin and tryptophan concentrations were measured (t = 0-60 min). Energy intake was assessed between t = 60-90 min. In lean individuals, Trp-3.0g, but not Trp-1.5g, slowed gastric emptying, reduced C-peptideAUC and increased glucagonAUC (all P < 0.05), but did not significantly decrease the blood glucose response to the drink, stimulate cholecystokinin or reduce mean energy intake, compared with control. In obese individuals, Trp-3.0g, but not Trp-1.5g, tended to slow gastric emptying (P = 0.091), did not affect C-peptideAUC, increased glucagonAUC (P < 0.001) and lowered blood glucose at t = 30 min (P < 0.05), and did not affect cholecystokinin or mean energy intake. In obese individuals, intragastrically administered tryptophan may reduce postprandial blood glucose by slowing gastric emptying; the lack of effect on mean energy intake requires further investigation.


Assuntos
Depressores do Apetite/administração & dosagem , Bebidas , Glicemia/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Alimentos Formulados , Obesidade/tratamento farmacológico , Triptofano/administração & dosagem , Administração Oral , Adulto , Depressores do Apetite/efeitos adversos , Bebidas/efeitos adversos , Biomarcadores/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Colecistocinina/sangue , Método Duplo-Cego , Alimentos Formulados/efeitos adversos , Esvaziamento Gástrico/efeitos dos fármacos , Glucagon/sangue , Humanos , Masculino , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Período Pós-Prandial , Austrália do Sul , Fatores de Tempo , Resultado do Tratamento , Triptofano/efeitos adversos
20.
Respiration ; 95(2): 139-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29485420

RESUMO

We report the case of a 50-year-old woman with anorexigen-induced pulmonary arterial hypertension treated with epoprostenol, who presented with Trousseau's sign, leading to the diagnosis of severe hypocalcemia for which substitution was started (initially orally, followed by intravenous substitution). After further analysis, we assume that epoprostenol-induced diarrhea caused malabsorption (as other reasons were excluded), leading to nutritional osteomalacia with secondary hyperparathyroidism. We discovered that even more severe hypocalcemia was induced by the treatment with the anti-osteoporotic drug denosumab, which was started after the diagnosis of osteoporosis on bone densitometry. In our opinion, clinicians have to be aware that in patients with malabsorption, antiresorptive therapy can induce dangerous and even life-threatening hypocalcemia, even in patients with normal renal function.


Assuntos
Anti-Hipertensivos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Epoprostenol/efeitos adversos , Hipocalcemia/induzido quimicamente , Depressores do Apetite/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/complicações , Feminino , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Pessoa de Meia-Idade
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