Background: Lifestyle interventions for weight loss are currently not individualized to underlying pathophysiology and behavioral traits in obesity. We aim to compare the outcome of a standard lifestyle intervention (SLI) to phenotype-tailored lifestyle interventions (PLI) on weight loss, cardiometabolic risk factors and physiologic variables contributing to obesity.
Methods: This is a 12-week non-randomized clinical trial comparing two forms of lifestyle interventions in patients with obesity. All participants completed in-person phenotype testing at baseline and after 12 weeks. In the first phase, participants were assigned to SLI with a low-calorie diet (LCD), moderate physical activity, and weekly behavioral therapy sessions. In the second phase, other participants were assigned to PLI according to phenotype: abnormal satiation (time-restricted volumetric LCD); abnormal postprandial satiety (LCD with pre-meal protein supplementation); emotional eating (LCD with intensive behavioral therapy); and abnormal resting energy expenditure (LCD with post-workout protein supplementation and high-intensity interval training). The primary outcome was total body weight loss in kg. Linear models estimated the association of study group allocation and study endpoints adjusting for age, sex, and baseline weight.
Findings: There were 165 participants: 81 SLI (mean [SD] age 42·9 [12] years; 79%women; BMI 38·0 [6]) and 84 PLI (age 44·8 [12·2] years; 83% women; BMI 38·7 [6·9]); 146 completed the 12-week programs. The weight loss was -6·9 kg (95%CI, -8·1, -5·7) with PLI vs. -3·5 kg (95%CI, -4·5, -2·5) with SLI (difference, -3·3 kg [95%CI, -4·8 to -1·9]; P<0·001).
Interpretation: Phenotype-tailored lifestyle interventions may result in significant weight loss, but a randomized controlled trial is required to confirm causality.
FUNDING: Mayo Clinic; NIH (K23-DK114460).