Structured lifestyle modification as an adjunct to obesity pharmacotherapy: there is much to learn.

We are at the start of an exciting new era of very effective pharmacotherapy for patients with obesity, with the latest generation of drugs approaching the efficacy of obesity surgery. Clinical trials of obesity drugs tend to emphasise the importance of participation in some form of structured lifestyle intervention for all trial participants. This usually consists of advice to reduce calorie intake and increase moderate to vigorous physical activity. There is strong evidence that structured lifestyle modification programmes improve health in patients with obesity and related disorders. However, there is no specific evidence that they improve the response to obesity medications. This is because of the way that drug trials for patients with obesity have traditionally been designed, with participants in the active drug treatment group being compared to participants on placebo drug treatment, but with both groups always receiving the same structured lifestyle intervention. While this approach is entirely reasonable, it makes it impossible to draw any inferences about the efficacy of structured lifestyle modification to augment the response to drug therapy. Given this genuine equipoise, a critical step in ensuring that our treatment of patients with obesity is robustly evidence-based is to determine whether "drug plus lifestyle" offer any advantage over "drug plus placebo" in large, well-designed and adequately powered clinical trials. We also need to determine the cost-effectiveness of these programmes.