Emerging concepts in the medical and surgical treatment of obesity.
The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.
Aylwin
Simon
S
Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, UK.
Al-Zaman
Yayha
Y
D000273:Adipose Tissue / Q000473:pathology; D000682:Amyloid / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications; D001069:Appetite Regulation / Q000502:physiology; D050110:Bariatric Surgery / Q000009:adverse effects / Q000379:methods; D015992:Body Mass Index; D016642:Bupropion / Q000627:therapeutic use; D002766:Cholecystokinin / Q000627:therapeutic use; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003503:Cyclobutanes / Q000627:therapeutic use; D003863:Depression / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D054439:Ghrelin / Q000627:therapeutic use; D006801:Humans; D050152:Intra-Abdominal Fat / Q000473:pathology; D058228:Islet Amyloid Polypeptide; D007555:Isoxazoles / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D020738:Leptin / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000188:drug therapy; D008687:Metformin / Q000627:therapeutic use; D009765:Obesity / Q000145:classification / Q000453:epidemiology / Q000517:prevention & control / Q000601:surgery* / Q000628:therapy*; D009767:Obesity, Morbid / Q000150:complications / Q000628:therapy; D000077403:Orlistat; D053772:Oxyntomodulin / Q000627:therapeutic use; D019894:Peptide YY / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011085:Polycystic Ovary Syndrome / Q000628:therapy; D011720:Pyrazoles / Q000627:therapeutic use; D000077285:Rimonabant; D020280:Sertraline / Q000627:therapeutic use; D020181:Sleep Apnea, Obstructive / Q000628:therapy; D013514:Surgical Procedures, Operative; D000077236:Topiramate; D000078305:Zonisamide
D000682:Amyloid; D000927:Anticonvulsants; D000928:Antidepressive Agents; D020934:Ciliary Neurotrophic Factor; D003503:Cyclobutanes; D054439:Ghrelin; D058228:Islet Amyloid Polypeptide; D007555:Isoxazoles; D007783:Lactones; D020738:Leptin; D053772:Oxyntomodulin; D010880:Piperidines; D011720:Pyrazoles; D005473:Fluoxetine; D016642:Bupropion; D000077236:Topiramate; D019894:Peptide YY; D005632:Fructose; D000078305:Zonisamide; D002766:Cholecystokinin; D008687:Metformin; D000077403:Orlistat; D020280:Sertraline; D000077285:Rimonabant; C058254:sibutramine