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

Abstract

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. To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases body weight. We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n=11) with uncomplicated hypertension treated with a β-blocker and anthropometrically matched controls (n=19) 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 (n=214), (b) hypertension outpatient (n=84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n=11140). 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 9.2 ± 1.2 kg (P=0.0002) higher among those attending the diabetes clinic, 17.2 ± 3.2 kg (P=0.004) higher among those attending the hypertension clinic and 5.2 ± 0.7 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. EE is reduced and body weight increased in chronic β-blocker users. We hypothesise that chronic β-blockade causes obesity by blunting EE.