Metabolic sequelae of Β-blocker therapy: weighing in on the obesity epidemic

Background:Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with Β-blocker therapy in the obese modern population is unknown.Objective:To determine whether chronic Β-blocker therapy reduces energy expenditure (EE) and increases body weight.Methods:We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n11) with uncomplicated hypertension treated with a Β-blocker and anthropometrically matched controls (n19) and (ii) three cross-sectional studies comparing body weight, body mass index (BMI) and waist circumference between Β-blocker treated and untreated patients from ambulatory patients attending (a) diabetes outpatient clinic (n214), (b) hypertension outpatient (n84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n11140).Results:Among weight-matched Β-blocker users, diet-induced thermogenesis, fat oxidation rate and weekly habitual activity were lower by 50% (P<0.01), 32% (P<0.04) and 30% (P<0.01), respectively, compared with controls. In Β-blocker treated patients, the adjusted mean body weight was 9.21.2 kg (P<0.0002) higher among those attending the diabetes clinic, 17.23.2 kg (P<0.004) higher among those attending the hypertension clinic and 5.20.7 kg (P<0.0003) higher at baseline among participants in the ADVANCE trial compared with patients not treated with Β-blockers. BMI displayed a similar difference.Conclusions:EE is reduced and body weight increased in chronic Β-blocker users. We hypothesise that chronic Β-blockade causes obesity by blunting EE.