Viewpoint: The latest anti-obesity drugs to gain approval


Professor Jason Halford, from the Department of Psychological Sciences, comments on the recent approval of two new anti-obesity drugs in Europe:

“This week saw wide press coverage of a new anti-obesity drug now potentially approved for use in Europe.  It is in fact one of two drugs likely to receive final approval. 

One agent, a combination of the nor-adrenaline and dopamine reuptake inhibitor Bupropion HCL 90mg and the selective opioid antagonist Naltrexone HCL 3mg (Orexigen Therapeutics)  is to be marketed as Mysimba™ in the EU. 

The second, and the one that dominated this weekend’s headlines, is human glucagon-like peptide-1 analogue Liraglutide 3 mg (Novo Nordisk) to be marketed under Saxenda™ .

It is already available globally at lower doses as Victoza™ for the treatment of type 2 diabetes.  Both target appetite systems in the periphery and/or the CNS reducing the motivation to consume and/or boosting satiety. 

They reduce energy intake and as used as an adjunct to diet and life style they have the potential to aid weight management.

The energy balance equation (energy intake minus energy expenditure) implies weight loss is easy (eat a bit less and do a bit more); however, changing life long habits is difficult especially in an environment which promotes overconsumption. 

Moreover, radically and prolonged adjustments in energy intake (500kcal a day) are needed to lose significant weight.  Irrespective of weight status dieting can impair cognitive function and induce dysphoria. 

Energy restriction reduces the level of important satiety hormones and the adiposity indicating hormones, while boosting the hunger hormone, undermining appetite control in a population who find maintaining healthy eating behaviour difficult. 

If we believe obesity is typically a consequence of overconsumption driven by our natural sensitivity to food stimuli and the pleasure derived from eating, then these processes could be effective targets for pharmacotherapy, and behavioural analysis can identify drugs that selectively affect desire to eat, enjoyment of eating, satiation or post-meal satiety, and thus maximize an individual’s capacity to successfully gain control over their appetite. 

Pharmacotherapies for obesity have been available for 60 years and a new generation of appetite supressing agents (4 in total) have already been approved in the US (Belviq, Qsymia, Contrave and Saxenda). 

However, regulators in Europe have been concerned with the risk benefit ratio (efficacy v potential psychiatric and CV events).  The history of anti-obesity drugs has been marked by regular withdrawal of agents due to addictiveness, cardiovascular (CV) or psychiatric effects (fenfluramine, sibutramine and rimonabant being recent examples). 

Currently the only drug widely available in the UK is the lipase inhibitor Orlistat (120mg prescription Xenical™ from Roche and 60mg OTC Alli™ from GlaxoSmithKline).  Orlistat, which prevents the absorption of dietary fat, produces relatively modest placebo subtracted weight loss but does significantly reduce cardio-metabolic risk factors and the incidence of type 2-diabetes . 

Successful weight maintenance remains a major issue in treatment.  Currently drugs are generally used to aid weight loss but evidence suggests they may equally be useful in preventing weight regain and maybe even in producing a second phase of dynamic weight loss. 

Pharmaceutical approaches to the management of body weight have traditionally focused on simple end points such as the absolute reduction in body weight. 

However, pharmacotherapy must fully address the contribution of appetite and eating behaviour in the aetiology and treatment of obesity. These include disinhibited eating, poorly controlled hunger, binge eating, and eating in response to negative emotions and stress. 

These factors are largely focused around our innate attraction to food and susceptibility to over-consumption.  No pharmaceutical treatment can substitute for the behavioural change that individuals must commit to in their own lives to lose weight. 

Interventions that alleviate the detrimental effects of dieting on appetite may be particularly effective in treating obesity. 

However, appetite is a dynamic system which responds to caloric restriction, and food preferences are habits that may be resistant to change, so in the context of weight maintenance as well as weight loss, novel anti-obesity drugs effectively help the obese manage their eating behaviour.”

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