Bench to bedside in appetite research: Lost in translation?

- Overweight and obesity present a huge health & economic burden.
- Most treatments are of limited efficacy.
- Few drug treatments are currently licensed.
- New drug development targets focus on polytherapies.
- Need for behavioural as well as molecular sophistication.

Despite substantial progress in our understanding of the complex bio-machinery involved in the regulation of appetite and energy homeostasis, few weight loss drugs are currently government-approved in the USA or Europe. While acknowledging novel drug monotherapies (such as Belviq® & Saxenda®), this review focuses on the various drug polytherapies that are currently attracting so much research interest. Unfortunately, however, the dependent variables in these new studies remain firmly rooted in outcome measures i.e. reduced food intake and bodyweight. Such evidence is clearly essential, as are physiological data bearing upon potential 'off-target' effects of any new treatment. However, as emphasised by many authors, this profiling has to be matched by sophisticated behavioural analysis addressing fundamental 'process' questions such as how such reductions in intake and/or bodyweight have been achieved. The value of behavioural analysis is exemplified, and it is argued that such a process-led approach should optimise the translation from preclinical to clinical development of candidate drugs, and avoid yet further expensive blind alleys.