The first decade of sibutramine and orlistat: a reappraisal of their expanding roles in the treatment of obesity and associated conditions

Abstract

Ancillary therapies for weight management, consisting mainly of diet and exercise programs that incorporate variable levels of lifestyle modification techniques, are frequently ineffective to achieve clinically meaningful weight loss and maintenance. Although pharmacological treatment of obesity is widely used in most countries, the number of available drugs is still very limited. The most widely used anti-obesity agents are sibutramine and orlistat, both available in clinical practice for about a decade. A large number of clinical trials have demonstrated that both agents are safe and well tolerated, with a level of efficacy in the moderate weight loss recommended by the most relevant clinical guidelines. Several studies have assessed the efficacy and safety of sibutramine and orlistat in adolescents and also for the treatment of some associated conditions in adults, including type 2 diabetes, polycystic ovary syndrome and binge eating disorder. The positive results of these studies suggest an expanding role for both agents, not only for the treatment of obesity, but also for associated conditions. After the efficacy of orlistat for the prevention of type 2 diabetes demonstrated in the XendoS study, the results of ScouT study are awaited for a better evaluation of sibutramine impact on cardiovascular outcomes. Arq Bras Endocrinol Metab. 2009;53(2):262-270. KeywordsObesity; pharmacological treatment; sibutramine; orlistat; safety; efficacy; weight loss. resumoA terapia anciã para controle do peso, que consiste principalmente em programas de dieta e exercício incorporando técnicas de mudança de estilo de vida de diversos níveis distintos, é frequentemente ineficaz em atingir uma perda e manutenção de peso clinicamente significativas. Apesar de amplamente utilizado na maioria dos países o tratamento farmacológico da obesidade, o número de medicamentos disponíveis ainda é muito limitado. os agentes antiobesidade mais utilizados são a sibutramina e o orlistate, ambos disponíveis na prática clínica há cerca de uma década. em um grande número de ensaios clínicos já se demonstrou que ambos agentes são seguros e bem tolerados, com um nível de eficácia consistente de perda de peso moderada que se recomenda nas principais diretrizes clínicas. Vários estudos avaliaram a eficácia e segurança da sibutramina e do orlistate em adolescentes e também para o tratamento de algumas condições associadas em adultos, incluindo o diabetes tipo 2, a síndrome dos ovários policísticos e o transtorno da compulsão alimentar periódica. os resultados positivos desses estudos sugerem que o papel dos dois medicamentos deverá ser expandido não apenas para o tratamento de um maior número de pacientes obesos, mas também para o tratamento de condições associadas. depois que o orlistate teve sua eficácia demonstrada na prevenção do diabetes tipo 2 por meio do estudo XendoS, os resultados do ScouT são aguardados para uma melhor avaliação do impacto da sibutramina sobre os desfechos cardiovasculares. Arq Bras Endocrinol Metab. 2009;53(2):262-2...

Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs

“…Lipids are absorbed upon hydrolysis, and inhibition of the lipases reduces the hydrolysis, thus decreasing the fat intake. In addition to weight loss, orlistat has been shown to improve conditions such as hypertension and type II diabetes (12). On the other hand, orlistat has been implicated with severe liver toxicity (13).…”

Incretin-based therapies for obesity treatment

“…Thus, the use of drugs should be considered when other non-pharmacological measures fail [5]. Today, drug treatment for obesity is very common [6].…”

“…In addition, drugs have adverse effects, which limits their clinical use [6,7]. Orlistat has been approved in Europe and the United States to treat obesity, but many patients cannot tolerate its gastrointestinal side effects [8].…”

Type 2 Diabetes Prevention Programs; How Far are we?

“…Type2 diabetes (T2D), which is the most common condition and a serious global health problem, accounts for 85% to 95% of all diabetes in high-income countries and may account for an even higher percentage in lowand middle-income countries. A further 316 million people or 6.9% of adults with Impaired Glucose Tolerance (IGT) are at risk from the habits and increase physical activity are the most effective strategies, representing the first steps of T2D prevention programs, while the effect of pharmacological interventions decreased after intervention was terminated [13][14][15][16][17][18]. Encouraged by these results, there have been many attempts to translate the prevention trials into community-based programs [8,[19][20][21].…”