Introduction Desire for a thinner body is common among adolescents and young adults and may occur even in the absence of excess weight. We aimed to characterise normal-weight young people who wanted to be thinner and identify factors independently associated with this desire. Methods This was a cross-sectional observational study based on structured computer-assisted telephone interviews conducted in February 2023 among 1000 adolescents and young adults aged 16–30 years in Spain. Data included self-reported anthropometry, weight perception, previous weight-management experiences, health-related attitudes, lifestyle behaviours, and social media use. Analyses focused on participants with normal weight, and Firth penalised logistic regression was used to identify independently associated factors. Results Overall, 57.1% of participants wanted to be thinner. Among those with normal weight (n = 686), 49.0% expressed this desire, whereas only 15.6% perceived themselves as having excess weight. Among participants with normal weight who wanted to be thinner, 92.0% had previously attempted weight loss; among previous attempters, recurrent attempts and the use of self-directed and online strategies were more frequent. Perceived excess weight [adjusted odds ratio (aOR) 13.75, 95% confidence interval (CI) 4.72–40.01] and previous weight-loss attempts (aOR 6.62, 95% CI 3.92–11.20) showed the strongest independent associations. Female sex, higher body mass index (BMI) within the normal range, greater interest in health, and lower physical activity frequency were also independently associated. Conclusions Among normal-weight adolescents and young adults, desire to be thinner identified a distinct weight-related behavioural pattern that extended beyond weight-status misperception. Its long-term psychological and metabolic significance remains uncertain and warrants prospective investigation.
Background: Orforglipron, an oral small-molecule glucagon-like peptide-1 receptor agonist, improved body weight and cardiometabolic parameters in the phase 3 ATTAIN-1 trial, but its efficacy and safety in adults with body mass index (BMI) of ≥27 to <30 kg/m 2 and adiposity-related complications have not been characterized. Adults with overweight and an adiposity-related complication are at substantial cardiometabolic risk, and obesity medications are recommended for this group. Methods: This was a post-hoc analysis of the ATTAIN-1 trial (NCT05869903), a phase 3, randomized, double-blind, placebo-controlled trial in which adults without diabetes and with obesity or overweight were randomized 3:3:3:4 to once-daily oral orforglipron 5.5, 9, or 17.2 mg or placebo for 72 weeks. The present analysis included the subset of randomized participants with BMI ≥27 to <30 kg/m 2 and ≥1 adiposity-related complication. Endpoints included change from baseline to Week 72 the percent change in body weight, BMI, categorical weight-loss, waist circumference, lipids, patient-reported outcomes, and safety. Effect estimates are reported using efficacy and treatment-regimen estimands. Efficacy endpoints were also reported per sex subgroup. Results: This analysis included 260 participants (orforglipron 5.5 mg: 56; 9 mg: 64; 17.2 mg: 62; placebo: 78). At Week 72, orforglipron was associated with greater mean percent body weight reduction (17.2 mg: −13.5%) versus placebo (−0.3%) (nominal p < 0.001). Females experienced up to −18.8% mean body weight reduction and males up to −10.0%. Orforglipron was associated with improvements in waist circumference, triglycerides, and low-density lipoprotein cholesterol, as well as improvements in patient-reported outcomes. Safety profile was consistent with previous trials with predominantly mild-to-moderate gastrointestinal events. Conclusion: In this post hoc analysis of ATTAIN-1, participants with BMI ≥27 to <30 kg/m 2 and ≥1 adiposity-related complication, orforglipron was associated with improvements in anthropometric and cardiometabolic parameters, with a safety profile broadly consistent with the overall ATTAIN-1 trial ( ClinicalTrials.gov identifier: NCT05869903).
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among individuals with obesity evaluated for metabolic and bariatric surgery (MBS) and may persist or recur despite substantial postoperative weight loss. This review examines the postoperative state as a dynamic model of hepatic metabolic reprogramming and gene–nutrition interaction, integrating surgical anatomy, dietary intake, nutrient absorption, metabolic response, weight trajectory, and inherited susceptibility. Methods This was a narrative clinical review informed by a structured literature search of MEDLINE (via PubMed), the Cochrane Library, and Epistemonikos (final search, August 3, 2026). Human evidence on hepatic outcomes after MBS, genetic determinants of liver disease, and postoperative nutritional exposures was prioritized; mechanistic and non-surgical human studies were considered only where direct postoperative evidence was limited. Results MBS rapidly reduces hepatic fat and improves insulin sensitivity, whereas resolution of metabolic dysfunction-associated steatohepatitis (MASH) and regression of fibrosis follow slower and partly dissociated trajectories. Genetic variants affecting hepatic lipid storage, lipid export, glucose-driven lipogenesis, and fibrogenesis may contribute to residual hepatic risk, but no study has jointly assessed genotype, repeated postoperative dietary exposure, and direct liver outcomes. Current evidence supports adequate protein intake, procedure-specific micronutrient supplementation, sustained dietary quality, metabolic risk control, alcohol assessment, and phenotype-guided liver surveillance regardless of genotype. Pharmacotherapy with demonstrated histological efficacy in MASH may be considered for residual MASH or weight recurrence, although it has not been evaluated specifically after MBS. Conclusions Genetic information may refine the interpretation of residual hepatic risk, but genotype-guided procedure selection, dietary patterns, macronutrient targets, or supplement doses are not supported. Prospective, adequately powered, multi-ancestry studies integrating longitudinal nutrition, genetic susceptibility, and direct hepatic outcomes are needed to determine whether genotype-informed nutrition improves outcomes beyond high-quality phenotype-guided care.
