Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy

Abstract

ObjectiveObesity pharmacotherapies result in an exponential time course for energy intake whereby large early decreases dissipate over time. This pattern of declining drug efficacy to decrease energy intake results in a weight loss plateau within approximately one year. We aimed to elucidate the physiology underlying the exponential decay of drug effects on energy intake.MethodsWe examined the placebo-subtracted energy intake time courses during long-term obesity pharmacotherapy trials for 14 different drugs or drug combinations within the theoretical framework of a proportional feedback control system regulating human body weight.ResultsAssuming each obesity drug had a relatively constant effect on average energy intake and did not affect other model parameters, our model correctly predicted that long-term placebo-subtracted energy intake was linearly related to early reductions in energy intake according to a pre-specified equation with no free parameters. The simple model explained about 70% of the variance between drug studies with respect to the long-term effects on energy intake, although a significant proportional bias was evident.ConclusionsThe exponential decay over time of obesity pharmacotherapies to suppress energy intake can be interpreted as a relatively constant effect of each drug superimposed on a physiological feedback control system regulating body weight.