Recent advancements in drug treatment of obesity

Abstract

ABSTRACT-The prevalence of obesity is rising worldwide, with the UK having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately £2 billion each year. Lifestyle modification remains the cornerstone of antiobesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesityrelated prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved longterm medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials. KEY WORDS: Obesity, pharmacotherapy BackgroundThe incidence of obesity is rising worldwide and the UK is amongst the worst-affected countries, with 30% of adults in the UK being obese. In addition, 30% of UK children aged 2 to 15 are overweight or obese. 1 The prevalence of obesity in the UK population is projected to reach 50% by 2050 (Fig 1), 2,3 with the cost of this condition and its associated co-morbidities predicted to cost the NHS some £2 billion per year by 2030. 3 The terms 'overweight' and 'obese' are defined as having a body mass index (BMI) greater than 25 kg/m 2 and 30 kg/m 2 , respectively. These values should, however, be used with caution as BMI is not a direct measure of adiposity. The National Institute of Clinical Excellence (NICE) recommends that waist circumference (above 88 cm for women or 102 cm for men being considered raised) is used in conjunction with BMI when describing the extent of obesity and predicting the extent of associated health risks. 4 The development of obesity is characterised by the interplay of nature and nurture. Genetic factors that are known to predispose individuals to obesity were probably once advantageous in resourcedeficient environments, where energy-conservation was essential for survival. With modern environments providing cheap energydense foods combined with increasingly sedentary lifestyles, these adaptive responses result in unnecessary retention of energy-rich adipose tissue. 5 This increased mass, and the released chemokines, are deemed responsible for obesity-related morbidity and mortality from conditions such as type 2 diabetes, cardiovascular and liver disease, and cancers. 4 A growing body of evidence suggests that maternal obesity might increase the offspring's propensity to obesity in adulthood through epigenetic alteration of fetal physiology. 6 This is especially important in the UK, where about one in five women of reproductive age are obese, 7 as failure to address maternal obesity might be leading to developmental progr...

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

“…Antiobesity medications are categorized according to their mode of action, such as inhibitors of fat absorption, inhibitors of the endocannabinoid system, or modifiers of the central nervous system. 390,391 Orlistat is a pancreatic lipase inhibitor that binds to lipase in gut lumen and prevents the hydrolysis and absorption of *30% of the dietary fat contained in a meal. 392 Sibutramine, a selective inhibitor of neurotransmitter (serotonin and norepinephrine) reuptake, acts centrally to reduce food intake.…”

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

“…Most of current pharmacological approaches aimed at treating NAFLD consist in inhibiting either 1) fat absorption; 2) inflammation; 3) the endocannabinoid system; or 4) modulating the central nervous system (Carter et al, 2012). Notably, metformin was shown to improve liver injury, but this medication used in type 2 diabetes could not prevent fibrosis in patients with steatosis (Loomba et al, 2009).…”

A comparative study of efficacy of argyreia speciosa and orlistat for their anti-obesity action in high fat diet induced obese rats

“…NICE (National Institute for Health and Care Excellence) guidelines limit its use for 2 years. 7 In this study, it is observed that there is significant increase in serum lipids, such as Total Cholesterol (TC), Low Density Lipoprotein (LDL), and Triglycerides (TG) in obese animals. Further, there is a decrease in HDL/ LDL ratio.…”