Selection of Antiobesity Medications Based on Phenotypes Enhances Weight Loss: A Pragmatic Trial in an Obesity Clinic

Abstract

Little is known about the predictors of response to obesity interventions. Methods: In 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12-month, pragmatic, real-world trial performed in a weight management center, 312 patients were randomly assigned to phenotype-guided treatment or non-phenotype-guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months. Results: Four phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype-guided approach was associated with 1.75-fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non-phenotype-guided group (difference −6.9% [95% CI −9.4% to −4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype-guided group compared with 34% with non-phenotype-guided treatment group. Conclusions: Biological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.

Association of gastric emptying with postprandial appetite and satiety sensations in obesity

“…GE, gastric emptying; OAS, overall appetite score; VAS, visual analog scale increases ghrelin(42). Moreover, the identification of rapid GE can help to individualize treatment strategies in patients with obesity to achieve better weight-loss outcomes(43). Thus, in 2 pilot studies, we have shown that patients with obesity and rapid GE respond better to GLP-1 analogs, exenatide(24), and liraglutide(21).…”

“…GE, gastric emptying; OAS, overall appetite score; VAS, visual analog scale increases ghrelin(42). Moreover, the identification of rapid GE can help to individualize treatment strategies in patients with obesity to achieve better weight-loss outcomes(43). Thus, in 2 pilot studies, we have shown that patients with obesity and rapid GE respond The calorie intake of the next meal, or expected satiation, is influenced by the nutritional properties of the previous meal, homeostatic food intake signals, and learned behavior about expected satiation potential.…”

“…Thus, in 2 pilot studies, we have shown that patients with obesity and rapid GE respond better to GLP-1 analogs, exenatide(24), and liraglutide(21). More recently, abnormal postprandial satiety, defined as rapid GE, was identified as a key phenotype in a novel obesity classification based on pathophysiological and behavioral traits(43). Furthermore, the classification was used to guide antiobesity pharmacotherapy in a 312-patient pragmatic trial and showed that patients treated with liraglutide and abnormal postprandial satiety had 2 times more weight loss than patients with normal postprandial satiety(43).…”

“…More recently, abnormal postprandial satiety, defined as rapid GE, was identified as a key phenotype in a novel obesity classification based on pathophysiological and behavioral traits(43). Furthermore, the classification was used to guide antiobesity pharmacotherapy in a 312-patient pragmatic trial and showed that patients treated with liraglutide and abnormal postprandial satiety had 2 times more weight loss than patients with normal postprandial satiety(43). This suggests the clinical relevance of GE as an objective measurement of postprandial satiety.…”

Selection of antiobesity medications based on phenotypes enhances weight loss: A pragmatic trial in an obesity clinic

“…We want to apologize to the readers of our recent article published in Obesity (1) for the error in the information regarding clinical trial registration and the lack of clarity in describing the study design. Both issues are addressed in this corrigendum.…”