Quantitative gastrointestinal and psychological traits associated with obesity can differentiate between obesity phenotypes and predict response to weight-loss pharmacotherapy, according to recent study findings.
Aiming to identify quantitative GI and psychological traits associated with obesity, and to validate the utility of these traits in predicting response to weight-loss drugs, Michael Camilleri, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, and colleagues performed a study involving three cohorts totaling 509 adults (mean age, 37.5 ± 12.2 years; 67.2% females, 91% Caucasians) who were normal weight (n = 85), overweight (n = 158), obesity class I (n = 135) or obesity class II (n = 131).
They prospectively measured GI and psychological traits in 328 participants, and included data on 181 who had previously undergone the same measurements. Next, they evaluated associations between these traits with BMI and waist circumference, and searched for latent dimensions using principal component analysis of 231 prospectively studied participants. Finally, they performed a proof of concept, placebo-controlled trial of Qsymia (phentermine hydrochloride/topiramate, Vivus) in 24 patients with obesity to validate associations between the identified traits and response to weight-loss therapy.
Overall, “there were significant associations of obesity with larger calorie intake, higher gastric volume during fasting, accelerated gastric emptying of solids and liquids, lower postprandial peptide YY, and psychological/behavioral features (anxiety, depression, body image perception, exercise),” Camilleri told Healio Gastroenterology. “Approximately 81% of the variation of BMI was attributable to satiety or satiation (21%), gastric motility (14%), psychological/behavioral factors (13%) and gastric sensorimotor factors (11%).”
In comparing the two treatment groups, Camilleri and colleagues found that the patients assigned phentermine/topiramate extended release lost 1.42 ± 0.4 kg vs. those assigned placebo who lost 0.23 ± 0.4 kg (P = .03). Additionally, they found a differential effect of the pharmacotherapy on weight loss (P = .029) due to higher caloric intake at a prior satiety test giving those patients taking the medication a predisposition to greater weight loss.
“In the proof of concept study, weight loss in response to phentermine and topiramate was significantly associated with calorie intake at a prior buffet meal satiety test,” Camilleri said. “Thus, obese patients may be matched to pharmacotherapy directed to specific abnormalities, potentially enhancing drug efficacy in treatment of obesity.”
The phenotypes identified in this study “need to be validated prospectively in other studies and it remains to be seen whether they have predictive value to allow individualizing approaches to weight loss or refining current treatments,” Pankaj Jay Pasricha, MD, from Johns Hopkins School of Medicine, wrote in an accompanying editorial. “Further, even if these physiologic findings are valid, we do not know how easily hedonic eating behavior can override gastric signals. Nevertheless, the study has provided a basis for going forward for other investigators and its results will expand our current concepts about obesity to include gastric physiology and pathophysiology.” – by Adam Leitenberger
Disclosure: The researchers and Pasricha report no relevant financial disclosures.