Hormones play a role too. When an individual tries to lose weight, it triggers a powerful hormonal response that tells your body to regain the weight you lost. Cummings explains that because of this, the brain interprets a calorie drop as an energy deficiency, so after stopping weight-loss drugs, hormones that stimulate appetite increase while the rate at which you burn energy – the metabolic rate – decreases. “If these biological defences are strong enough, they can blunt the drug’s effectiveness,” he says.