Campos, Alejandro

ABSTRACT Objective This study compared the effects of phentermine‐topiramate‐ER (mid‐dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). Methods We conducted a 12‐month, randomized, double‐blind, placebo‐controlled trial at a single tertiary academic center in the United States (June 2020–June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m 2 ) were enrolled in the DELI program, consisting of in‐person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth‐enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine‐topiramate‐ER ( n = 42) or placebo ( n = 38) in addition to the DELI. Results At 3 months, the phentermine‐topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference −6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference −9.48 kg; p < 0.001). Participants receiving phentermine‐topiramate‐ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline ( p = 0.004). Conclusions Phentermine‐topiramate‐ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. Trial Registration ClinicalTrials.gov : NCT04408586

AbstractBackgroundFood intake is regulated by homeostatic and hedonic systems that interact in a complex neuro‐hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN.Material & MethodsDuring an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo‐continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30‐min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon‐like peptide (GLP‐1), and peptide YY (PYY) with every pCASL‐MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs).ResultsA total of 53 participants, 7 with AN, 17 with NW (body‐mass index [BMI] 18.5–24.9 kg/m2), and 29 with OB (BMI ≥30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post‐prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP‐1 and PYY, and no change in CCK.ConclusionConditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.

ImportanceNo retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).ObjectiveTo study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity.Design, Setting, and ParticipantsThis cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded.ExposuresWeekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months.Main Outcomes and MeasuresThe primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months.ResultsThe study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P &lt; .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P &lt; .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005).Conclusions and RelevanceThe results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.

We show how switching from a regular diet to an HCHF increases cholesterol absorption in patients with normal weight and obesity. The decrease in cholesterol absorption from an HCHF to an LCLF, on the other hand, was only seen in normal-weight controls, underlining the importance of body weight in this regulation. In addition, changes in caloric and fat content had an immediate and direct effect on hepatic bile acid production.

Food intake regulation in humans is a complex process controlled by the dynamic interaction of homeostatic and hedonic systems. Homeostatic regulation is controlled by appetitive signals from the gut, adipose tissue, and the vagus nerve, while conscious and unconscious reward processes orchestrate hedonic regulation. On the one hand, sight, smell, taste, and texture perception deliver potent food-related feedback to the central nervous system (CNS) and influence brain areas related to food reward. On the other hand, macronutrient composition stimulates the release of appetite signals from the gut, which are translated in the CNS into unconscious reward processes. This multi-level regulation process of food intake shapes and regulates human ingestive behavior. Identifying the interface between hormones, neurotransmitters, and brain areas is critical to advance our understanding of conditions like obesity and develop better therapeutical interventions. Neuroimaging studies allow us to take a glance into the central nervous system (CNS) while these processes take place. This review focuses on the available neuroimaging evidence to describe this interaction between the homeostatic and hedonic components in human food intake regulation.

AbstractObjectiveSatiety, defined as the duration of the sensation of fullness, is usually measured by validated visual analog scales (VAS) for appetite. Gastric function plays a key role in food intake regulation. However, the association between gastric emptying (GE) and VAS appetite is unknown.MethodsIn this cross‐sectional study, 134 participants (mean [SEM] age = 39 [0.8] years, mean [SEM] BMI = 38 [0.5] kg/m2, 67% females) completed simultaneous measurements of GE and VAS appetite. After a 320‐kcal meal, GE was measured by scintigraphy and appetite by validated 100‐mm VAS for 240 minutes. Satiation was defined as calories consumed to terminate meal and was measured by an ad libitum meal. GE, VAS, and ad libitum meal tests were measured on the same day. Percent of meal retention in the stomach, VAS area under curve (AUC0‐240 min), and overall appetite score (OAS) were calculated. Pearson correlation (ρ) determined the association of GE with VAS appetite and satiation. Appetite components were also analyzed by quartiles based on GE120 min.ResultsGE120 min was correlated with sensation of VAS hungerAUC(0‐240 min) (ρ = 0.24, p = 0.004), fullnessAUC(0‐240 min) (ρ = 0.16, p = 0.05), and OASAUC(0‐240 min) (ρ = 0.20, p = 0.02). Patients with rapid GE120 min had a mean increase in VAS hungerAUC(0‐240 min) by 32 mm/min (15.62%, p = 0.03) compared with normal/slow GE120 min.ConclusionsGE is associated with the sensations of appetite, and rapid GE is associated with increased appetite, which may contribute to weight gain.