RESUMEN
The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation.
Asunto(s)
Fármacos Antiobesidad , Naltrexona , Obesidad , Pérdida de Peso , Humanos , Fármacos Antiobesidad/uso terapéutico , Naltrexona/uso terapéutico , Cirugía Bariátrica/métodos , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Liraglutida/uso terapéutico , Bupropión/uso terapéutico , Topiramato/uso terapéutico , Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia. Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16â¯964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants). Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.
Asunto(s)
Fármacos Antiobesidad , Dieta Saludable , Obesidad , Femenino , Humanos , Masculino , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Bupropión/uso terapéutico , Bupropión/efectos adversos , Combinación de Medicamentos , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Fructosa/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Lactonas/uso terapéutico , Lactonas/efectos adversos , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Naltrexona/uso terapéutico , Naltrexona/efectos adversos , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Fentermina/efectos adversos , Topiramato/uso terapéutico , Topiramato/efectos adversos , Pérdida de Peso/efectos de los fármacos , Terapia Combinada/métodosRESUMEN
PURPOSE: The aim of this study was to systematically analyze the prescription trends of medical narcotic appetite suppressants in South Korea. MATERIALS AND METHODS: Data was extracted from the Narcotics Information Management System dataset from 2020, which encompasses nationwide information concerning the use of medical narcotics. The selected variables for this study included the types of prescribed medical narcotic appetite suppressants, gender, age, region, and the category of medical institution. Regional prescription trends were compared by utilizing the defined daily doses for statistical purposes (S-DDD). RESULTS: The prescription of medical narcotic appetite suppressants was predominantly for females (94%), with the highest prescription rates identified in the 30-40 age group. The majority of these prescriptions were dispensed by clinics. Within the category of narcotic appetite suppressants, phentermine and phendimetrazine were found to have higher prescription rates. Notably, the region of Daegu recorded the highest S-DDD value (12.66) in phentermine consumption. CONCLUSION: Our findings underscore the need for governmental policy and guidance to address the risks linked to the long-term use of medical narcotic appetite suppressants. This is crucial to ensure their safe and efficacious prescription and administration.
Asunto(s)
Depresores del Apetito , Narcóticos , Humanos , Femenino , Masculino , Adulto , República de Corea , Persona de Mediana Edad , Depresores del Apetito/uso terapéutico , Narcóticos/uso terapéutico , Fentermina/uso terapéutico , Anciano , Prescripciones de Medicamentos/estadística & datos numéricos , Adolescente , Adulto Joven , Niño , Pautas de la Práctica en Medicina/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , PreescolarRESUMEN
BACKGROUND: Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important. OBJECTIVES: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. METHODS: This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. RESULTS: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions. CONCLUSIONS: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.
Asunto(s)
Obesidad Infantil , Fentermina , Pérdida de Peso , Humanos , Femenino , Masculino , Estudios Retrospectivos , Obesidad Infantil/epidemiología , Obesidad Infantil/terapia , Fentermina/uso terapéutico , Niño , Adolescente , Fármacos Antiobesidad/uso terapéutico , Resultado del Tratamiento , Índice de Masa Corporal , Conducta de Reducción del Riesgo , Estilo de VidaRESUMEN
PURPOSE: A significant proportion of patients experience insufficient weight loss or weight regain after bariatric surgery. There is a paucity of literature describing anti-obesity medication (AOM) use following bariatric surgery. We sought to identify prevalence and trends of AOM use following bariatric surgery. MATERIALS AND METHODS: We utilized the IBM Explorys® database to identify all adults with prior bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy). Those prescribed AOMs (semaglutide, liraglutide, topiramate, phentermine/topiramate, naltrexone/bupropion, orlistat) within 5 years of surgery were further identified. Data was analyzed to characterize AOM utilization among different age, demographic, and comorbid populations. RESULTS: A total of 59,160 adults with prior bariatric surgery were included. Among AOMs studies, prevalence of use was highest for topiramate (8%), followed by liraglutide (2.9%), phentermine/topiramate (1.03%), naltrexone/bupropion (0.95%) semaglutide (0.52%), and orlistat (0.17%). Age distribution varied, with the highest utilization among those age 35-39 years for topiramate, 40-44 years for phentermine/topiramate and naltrexone/bupropion, 45-49 years for semaglutide, and 65-69 years for liraglutide and orlistat. African American race was associated with higher utilization across all AOMs. Among comorbidities, hypertension, hyperlipidemia, and diabetes mellitus were most associated with AOM use. CONCLUSION: Despite a relatively high incidence of weight regain, AOMs are underutilized following bariatric surgery. It is imperative that barriers to their use be addressed and that AOMs be considered earlier and more frequently in patients with insufficient weight loss or weight regain after bariatric surgery.
Asunto(s)
Fármacos Antiobesidad , Artritis , Cirugía Bariátrica , Enfermedades del Tejido Conjuntivo , Derivación Gástrica , Pérdida Auditiva Sensorineural , Obesidad Mórbida , Desprendimiento de Retina , Adulto , Humanos , Orlistat , Topiramato/uso terapéutico , Liraglutida/uso terapéutico , Naltrexona/uso terapéutico , Bupropión , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Fármacos Antiobesidad/uso terapéutico , Fentermina/uso terapéutico , Pérdida de Peso , Aumento de PesoRESUMEN
The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.
Asunto(s)
Fármacos Antiobesidad , Humanos , Fármacos Antiobesidad/uso terapéutico , Fentermina/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Orlistat/uso terapéutico , Liraglutida/uso terapéuticoRESUMEN
BACKGROUND: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. METHODS: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. CONCLUSION: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.
Asunto(s)
Fármacos Antiobesidad , Obesidad Mórbida , Obesidad Infantil , Adolescente , Niño , Humanos , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/farmacología , Fructosa/uso terapéutico , Obesidad Infantil/tratamiento farmacológico , Fentermina/uso terapéutico , Topiramato/uso terapéutico , Pérdida de Peso , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93â¯620 per QALY relative to no treatment in this simulated cohort of 10â¯000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1â¯079â¯480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100â¯000 to $150â¯000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100â¯000 to $150â¯000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100â¯000 to $150â¯000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.
Asunto(s)
Fármacos Antiobesidad , Obesidad Mórbida , Humanos , Femenino , Adolescente , Niño , Masculino , Fármacos Antiobesidad/uso terapéutico , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/cirugía , Análisis Costo-Beneficio , Orlistat/uso terapéutico , Topiramato/uso terapéutico , Liraglutida/uso terapéutico , Obesidad/tratamiento farmacológico , Fentermina/uso terapéuticoRESUMEN
INTRODUCTION: Management of patients with BMI≥50 kg/m2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage. METHODS: Patients with BMI≥50 kg/m2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston-Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46-15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP. RESULTS: By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01). CONCLUSIONS: Patients with BMI≥50 kg/m2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this.
Asunto(s)
Laparoscopía , Obesidad Mórbida , Humanos , Antihipertensivos/uso terapéutico , Gastrectomía/efectos adversos , Obesidad/cirugía , Obesidad Mórbida/cirugía , Obesidad Mórbida/etiología , Fentermina/uso terapéutico , Estudios Retrospectivos , Topiramato , Resultado del TratamientoRESUMEN
OBJECTIVE: Novel antiobesity treatments are highly effective in recent clinical trials. Access to these medications is needed to supplement lifestyle and surgical interventions for millions living with obesity worldwide, but high prices are limiting. This study aimed to review current treatment costs and calculate potential estimated minimum prices (EMPs). METHODS: The authors searched national drug price databases across various countries for orlistat, naltrexone-bupropion, topiramate-phentermine, liraglutide, semaglutide, and tirzepatide. EMPs for antiobesity medications were calculated using established methodology, using active pharmaceutical ingredients (API) from the Panjiva database. EMPs were calculated per 30-day course and include costs of active pharmaceutical ingredients, excipients, formulation, taxation, and 10% profit margin. RESULTS: National prices of antiobesity medications were significantly higher than calculated EMPs. Semaglutide 30-day course prices ranged from $804 (United States) to $95 (Turkey) while the EMP was $40. Liraglutide prices ranged from $1418 (United States) to $252 (Norway) while the EMP was $50. Some oral treatments could be generically manufactured at very low costs per course ($7 for orlistat; $5 for phentermine/topiramate combination tablets), while naltrexone/bupropion was more expensive ($54). CONCLUSIONS: This study shows that certain weight loss treatments can be manufactured and sold profitably at low costs, but prices currently range widely between countries, limiting access for those in need.
Asunto(s)
Fármacos Antiobesidad , Liraglutida , Orlistat/uso terapéutico , Topiramato , Liraglutida/uso terapéutico , Naltrexona/uso terapéutico , Bupropión/uso terapéutico , Combinación de Medicamentos , Fármacos Antiobesidad/uso terapéutico , Fentermina/uso terapéutico , Costos de la Atención en Salud , Accesibilidad a los Servicios de SaludRESUMEN
ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el cual expone la evaluación de la eficacia y seguridad de fentermina/topiramato en pacientes adultos con obesidad que persisten sin pérdida de peso luego de terapia nutricional y actividad física a seis meses. ASPECTOS GENERALES: La obesidad es definida como una acumulación excesiva de grasa que puede perjudicar la salud de niños y adultos y se diagnóstica operacionalmente con un índice de massa corporal (IMC) igual o superior a 30 (MacMahon et al. 2009). La obesidad es una enfermedad crónica que aumenta el riesgo de complicaciones a largo plazo, genera un deterioro de la calidad de vida y disminuye la esperanza de vida (Blüher 2019). La prevalencia de este trastorno ha aumentado en los últimos 40 años con variaciones entre países (de 3.8 % en Japón a 38.2 % en Estados Unidos) (MP et al. 2018). En el Perú, la prevalencia de obesidad ha aumentado de 8.5 % en 1975 a 18.5 % en 2013, y a 24.6 % en 2020 (INEI 2020). La obesidad mórbida se presenta con mayor frecuencia en las mujeres (1.3 %) que en los varones (0.4 %) (Pajuelo Ramírez et al. 2019). La obesidad es considerada como un factor de riesgo para desarrollar enfermedades metabólicas, cardiovasculares, musculoesqueléticas, Alzheimer, depresión y algunos tipos de cáncer (Blüher 2019). Estas condiciones han generado que las muertes globales y los años de vida ajustados por discapacidad (AVAD) debido a la obesidad se dupliquen entre 1990 y 2017 en hombres (de 1.0 a 2.3 millones de muertes, y de 31.9 a 77.0 millones de AVAD) y mujeres (de 1.2 a 2.4 millones de muertes, y de 33.1 a 70.7 millones de AVAD) (Dai et al. 2020). En este sentido, reducir la carga de enfermedad y disminuir la prevalencia de la obesidad son prioridades sanitarias para la Organización Mundial de la Salud (WHO 2016). METODOLOGÍA: Se realizó una búsqueda sistemática, amplia y exhaustiva, en las bases de datos bibliográficas PubMed, The Cochrane Library y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). Asimismo, se realizó una búsqueda dentro de la información generada en las páginas web de grupos o instituciones que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales corno: el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), la Haute Authorité de Santé (HAS), el Institute for Quality and Efficiency in HealthCare (IQWiG), el Institute for Clinical and Economic Review (ICER) y en la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), y en las principales instituciones o sociedades especializadas en endocrinología: la American Association of Clinical Endocrinology, la Obesity Society, la Endocrine Society, y la European Association for the Study of Obesity. Además, se llevó a cabo una búsqueda manual en el motor de búsqueda Google utilizando los términos: "Obesity guidelines"; revisando en las diez primeras páginas de resultados, a fin de poder identificar otras publicaciones de relevancia que pudiesen haber sido omitidas por la estrategia de búsqueda o que no hayan sido publicadas en las bases de datos bibliográficas consideradas. Finalmente, se realizó una búsqueda manual en ClinicalTrials.gov para identificar ensayos clínicos aleatorizados (ECA) en curso o que o hayan sido publicados aún. Se elaboraron estrategias de búsqueda en bases de datos bibliográficas y sitios web para obtener la evidencia científica que permita responder a la pregunta PICO. Las estrategias de búsqueda incluyeron términos relacionados con la intervención, población de interés y tipo de estudio. Se emplearon términos MeS1-11, así como, términos de lenguaje libre, junto con operadores booleanos para cada una de las bases de datos elegidas para la búsqueda. RESULTADOS: Luego de la búsqueda bibliográfica realizada hasta el 19 de septiembre del 2022, se identificaron: cuatro GPC (AHA/ACC/TOS, 2013; NICE, 2014; ES, 2015; MSPS, 2016) que emiten recomendaciones para el tratamiento de pacientes con obesidad y no han respondido a la terapia de cambios de estilos de vida. También se incluyó una RS (Khera et al., 2016) y tres ECA fase III (Allison et al., 2012; Gadde et al., 2011; Garvey et al., 2012). Por otro lado, se excluyeron seis GPC: una (SIGN, 2010) porque fue publicada antes de la primera autorización de comercialización de fentermina/topiramato; y cuatro (MSA 2014; AACE, 2016; OC/CAE3PS, 2020; VA/DoD, 2020) porque no brindan recomendaciones específicas para la población objetivo del presente dictamen. Además, se excluyeron tres RS (Xiang-Guo et al., 2021; Singh et al., 2020; Shi et al., 2022) porque incluyeron los mismos ECA pivotales que la RS incluida en el dictamen (Khera et al., 2016), pero tuvieron menor calidad metodológica según la herramienta AMSTAR. Finalmente, se excluyó un estudio (Kolotkin et al., 2015) que evaluó la calidad de vida mediante un análisis combinado de datos a nivel de paciente (pooled analysis of patient levet data) de cuatro ECA de fase III. Este estudio se excluyó porque el análisis combinado no tomó en cuenta las diferencias en los diseños de estudio de los cuatro ECA. Por ello, los resultados de calidad de vida fueron analizados en cada estudio, individualmente. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI no aprueba el uso de fentermina/topiramato en pacientes adultos con obesidad que persisten sin pérdida de peso luego de terapia nutricional y actividad física a seis meses, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud. Se recomienda a los especialistas que, en caso de identificar nueva evidencia que responda a la población de la PICO de interés, envíen sus propuestas para ser evaluadas en el marco de la Directiva N° 003-IETSI-ESSALUD-2016.
Asunto(s)
Humanos , Adulto , Fentermina/uso terapéutico , Ejercicio Físico , Terapia Nutricional/instrumentación , Topiramato/uso terapéutico , Obesidad/tratamiento farmacológico , Eficacia , Análisis Costo-BeneficioRESUMEN
BACKGROUND & AIMS: Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap. CONCLUSIONS: In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.
Asunto(s)
Fármacos Antiobesidad , Adulto , Humanos , Orlistat/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Sobrepeso/tratamiento farmacológico , Liraglutida/uso terapéutico , Bupropión/uso terapéutico , Naltrexona/uso terapéutico , Topiramato/uso terapéutico , Pérdida de Peso , Dietilpropión/uso terapéutico , Fentermina/uso terapéutico , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/terapia , Hidrogeles/uso terapéuticoRESUMEN
OBJECTIVE: This study aimed to demonstrate noninferiority using telehealth in treating obesity with phentermine in patients with BMI ≥ 27 kg/m2 with comorbidities or BMI ≥ 30 compared with the standard in-person approach over a 90-day period. METHODS: A 12-week, randomized, prospective, single-center, open label trial compared the use of virtual visits versus in-person visits for the treatment of obesity using phentermine. The primary end point was percentage mean change in body weight from baseline to 12 weeks. A noninferiority approach assuming a 3% noninferiority region was used to assess effect size differences. RESULTS: The weight loss in the virtual visit arm was noninferior to the in-person arm at all time points. At 12 weeks, the mean change in weight was -6.5% among the virtual group and -7.7% among the in-person group. In addition, 65% of virtual patients and 71% of in-person patients demonstrated a weight reduction of at least 5%. There was no difference in medication tolerance, adherence, and compliance. CONCLUSIONS: These results indicate that the virtual obesity pharmacotherapy visits in adults aged 18 to 65 years prescribed phentermine are effective and noninferior in achieving meaningful weight loss after 12 weeks. Future clinical trials are needed to better assess the effectiveness of televisits for obesity pharmacotherapy.
Asunto(s)
Obesidad , Sobrepeso , Adulto , Humanos , Sobrepeso/tratamiento farmacológico , Estudios Prospectivos , Obesidad/tratamiento farmacológico , Fentermina/uso terapéutico , Pérdida de PesoRESUMEN
OBJECTIVE: Hepatic steatosis is associated with increased surgical complications in bariatric surgery patients. We aimed to evaluate the effect of phentermine in reducing hepatic steatosis, adipose tissue, and surgical complications in patients undergoing bariatric surgery. METHODS: This was a two-arm, double-blind, randomized, controlled pilot trial of 64 adult subjects with BMI >35 kg/m2 selected for bariatric surgery randomized into phentermine group (15 mg once daily) or placebo group for 8 weeks. Both groups adhered to a hypocaloric diet (500 calories/day) and an individualized exercise program. The primary endpoint was reducing the frequency of hepatic steatosis measured by ultrasound and reducing adipose tissue through fat mass in total kilograms or percentage. Key secondary points were the prevalence of surgical complications. Baseline and final biochemical parameters and blood pressure too were assessments. RESULTS: In the phentermine group, the frequency of hepatic steatosis decreased by 19%, and the percentage of patients with a normal ultrasound increased from 9% to 28% (p = 0.05). Likewise, the decrease in fat mass in kilograms was more significant in the phentermine group (56.1 kg vs. 51.8 kg, p = 0.02). A significant reduction in the HOMA-IR index was observed regardless of weight loss. No differences in surgical complications were observed between groups. Phentermine was well-tolerated; no differences were observed in the frequency of adverse events between the groups. CONCLUSIONS: Phentermine decreased the proportion of individuals with hepatic steatosis by 19% and promoted a more significant fat mass loss in kilograms among candidates for bariatric surgery.
Asunto(s)
Cirugía Bariátrica , Fentermina , Adulto , Cirugía Bariátrica/efectos adversos , Dieta Reductora , Humanos , Obesidad/complicaciones , Obesidad/cirugía , Fentermina/efectos adversos , Fentermina/uso terapéutico , Proyectos PilotoRESUMEN
PURPOSE OF REVIEW: Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology. RECENT FINDINGS: Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease. Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD.
Asunto(s)
Fármacos Antiobesidad , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Fármacos Antiobesidad/uso terapéutico , Liraglutida/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Metabolic risk for cardiovascular and other systems includes much more than just LDL cholesterol. This JCL Roundtable brings together 3 experts to address new opportunities to reduce the risks posed by obesity, diabetes, and fatty liver disease. Successful nutritional approaches to weight loss are diverse and need to be matched with individual preferences. Topiramate plus extended-release phentermine has been shown to promote meaningful weight loss in randomized trials, but the patented drug combination is expensive. Clinical experience suggests that generic topiramate and phentermine may also be effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown favorable tolerability and efficacy for cardiovascular disease in randomized trials, an achievement without precedent among earlier diabetes medications. These 2 drug classes differ in their effects. GLP-1 RAs decrease atherosclerotic cardiovascular events and also decrease hemoglobin A1c, body weight, blood pressure, and possibly diabetic renal disease. SGLT2 inhibitors are effective in reducing heart failure events even among nondiabetic patients. They also decrease progression of diabetic renal disease. The presence of nonalcoholic fatty liver disease signifies risk for atherosclerotic cardiovascular disease as well as cirrhosis and serious hepatic decompensation, including hepatocellular carcinoma. The key to identifying cirrhosis risk is to assess pre-emptively liver fibrosis, which can be predicted initially with blood test risk scores (e.g., FIB-4 index) and more definitively by transient elastography and other imaging techniques and/or liver biopsy. Some medications approved for the treatment of type 2 diabetes may reduce liver fat (SGLT2 inhibitors, insulin) or even reverse steatohepatitis in paired liver biopsy studies (GLP-1 RAs or pioglitazone) Overall the field of preventive metabolic medicine is expanding. Clinical lipidologists should become familiar with recent advances.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipoglucemiantes/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Masculino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Fentermina/uso terapéutico , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Topiramato/uso terapéutico , Pérdida de PesoRESUMEN
Background: Orlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks. Methods: A total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism. Results: The experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7ß-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups. Conclusion: Orlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation.
Asunto(s)
Fármacos Antiobesidad , Oxiesteroles , Adulto , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Colesterol , Método Doble Ciego , Humanos , Lactonas/farmacología , Lactonas/uso terapéutico , Lipasa/uso terapéutico , Obesidad/inducido químicamente , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Orlistat/uso terapéutico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Fentermina/uso terapéutico , Pérdida de PesoRESUMEN
OBJECTIVE: Modest weight loss (5%-10%) is clinically meaningful in patients with overweight or obesity. However, greater weight loss may be required to achieve improvements in or remission of certain weight-related complications. Therefore, this study reviewed the effect of large weight loss (≥10%). Most studies reporting large weight loss and relevant outcomes used bariatric surgery or lifestyle modifications. RESULTS: Benefits of large weight loss were observed in patients with various overweight- or obesity-related complications, including improvements in comorbidities such as type 2 diabetes and hypertension. Improvements in glucose metabolism and cardiovascular risk factors were observed in patients who achieved large weight loss through lifestyle interventions or pharmacotherapy (phentermine/topiramate 15/92 mg once daily or subcutaneous semaglutide 2.4 mg once weekly). Other benefits associated with large weight loss included reduced cancer risk and improvements in knee osteoarthritis, sleep apnea, fertility-related end points, and health-related quality of life. While costly, bariatric surgery is currently the most cost-effective intervention, although most weight-management programs are deemed cost-effective. CONCLUSIONS: Overall, large weight loss has a major beneficial impact on overweight- and obesity-related complications. Large weight loss should be the main treatment target when modest weight loss has had insufficient effects on obesity-related complications and for patients with severe obesity.
Asunto(s)
Fármacos Antiobesidad , Diabetes Mellitus Tipo 2 , Fármacos Antiobesidad/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Humanos , Obesidad/tratamiento farmacológico , Obesidad/terapia , Sobrepeso/tratamiento farmacológico , Sobrepeso/terapia , Fentermina/uso terapéutico , Calidad de Vida , Topiramato/uso terapéutico , Pérdida de PesoRESUMEN
BACKGROUND: Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine-topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports. CASE PRESENTATION: A 35-year-old Caucasian male with a body mass index of 41.7 kg/m2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine-topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred. CONCLUSIONS: Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine-topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.