OBJECTIVE: This study aimed to investigate the associations of gestational weight gain (GWG) and GWG trajectory with children's neurodevelopment at age three. METHODS: This prospective analysis included 4177 mother-child...OBJECTIVE: This study aimed to investigate the associations of gestational weight gain (GWG) and GWG trajectory with children's neurodevelopment at age three. METHODS: This prospective analysis included 4177 mother-child pairs from the Jiangsu Birth Cohort. GWG was assessed both as categories (insufficient/optimal/excessive) and trajectories based on repeated prenatal measurements. Children's neurodevelopment at age three was assessed using the Bayley Scales of Infant and Toddler Development, Version-III Screening Test. A Robust Poisson regression model was used to examine the associations of GWG categories and trajectories with children's neurodevelopment. RESULTS: Compared with children of mothers with optimal GWG, those exposed to excessive GWG had 50% higher noncompetent cognitive risk (RR = 1.50), while insufficient GWG increased noncompetent fine motor risk by 30% (RR = 1.30). Notably, the association between insufficient GWG and noncompetent cognitive development was observed only among those with breastfeeding duration ≤ 12 months (RR = 2.07), not among those breastfeeding > 12 months (RR = 0.72). The "Slow-Rapid" GWG trajectory was associated with elevated risks of both noncompetent cognitive development (RR = 2.51) and expressive communication (RR = 1.94). CONCLUSIONS: Excessive GWG, insufficient GWG, and the Slow-Rapid GWG trajectory showed associations with children's noncompetent neurodevelopment. As GWG is a modifiable factor, these findings could inform early intervention for high-risk mother-child dyads.
OBJECTIVE: Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellit...OBJECTIVE: Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus. This systematic review and network meta-analysis aims to compare the efficacy of these agents against each other. METHODS: A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025. Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included. A frequentist random-effects network meta-analysis was performed using R 4.3.3. RESULTS: Of 1420 articles identified, 15 RCTs with 14,059 patients were included. All agents significantly reduced body weight compared to placebo. The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg. Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not. CONCLUSIONS: Tirzepatide, particularly at higher doses, provides the greatest weight reduction in adults without diabetes. Future studies should evaluate discontinuation, weight regain, metabolic outcomes, cost-effectiveness, and patient preferences.
Liu L, Xiong G, Zhao H
… +3 more, Shi H, Liang M, Nahata MC
Obesity (Silver Spring)
· 2026 May · PMID 41936389
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OBJECTIVE: This study assessed national trends in weight loss attempts, clinically meaningful weight loss, and associated strategies among US adolescents with overweight or obesity. METHODS: We analyzed National Health a...OBJECTIVE: This study assessed national trends in weight loss attempts, clinically meaningful weight loss, and associated strategies among US adolescents with overweight or obesity. METHODS: We analyzed National Health and Nutrition Examination Survey (NHANES) 1999-2023 data for 2708 adolescents aged 16-19 years with overweight or obesity. Weight loss attempts and strategies were self-reported. Clinically meaningful weight loss was defined as ≥ 5% and ≥ 10% body weight reductions or a ≥ 0.2 reduction in body mass index (BMI) z-score over the prior year. Survey-weighted logistic regression assessed temporal trends and associations between strategies and weight loss success. RESULTS: The prevalence of weight loss attempts increased from 53.9% in 1999-2000 to 65.7% in 2021-2023 (p for trend < 0.001). Overall, 26.96% achieved a ≥ 5% weight loss and 12.58% achieved a ≥ 10% weight loss; 34.34% achieved a ≥ 0.2 BMI z-score reduction. Exercise and dietary changes were the most reported strategies. Reducing sugar intake (OR, 2.16) and prescription medication use (OR, 2.55) were associated with achieving a ≥ 5% weight loss, and prescription medication use (OR, 3.59) was also associated with achieving a ≥ 10% weight loss. Sugar intake reduction (OR, 1.89) and prescription medication use (OR, 2.73) were associated with achieving a ≥ 0.2 reduction in BMI z-score. CONCLUSIONS: Weight loss attempts increased over time, but clinically meaningful weight loss remained uncommon. Improved access to evidence-based, developmentally appropriate interventions is needed.
Denstel KD, Mire EF, Martin CK
… +9 more, Apolzan JW, Arnold CL, Davis TC, Lavie CJ, Newton RL, Zhang D, Price-Haywood EG, Katzmarzyk PT, PROPEL Research Group
OBJECTIVE: This study examined (1) the association between weight loss and changes in health-related quality of life (HRQoL) and (2) treatment response heterogeneity among patients in a weight loss intervention. METHODS:...OBJECTIVE: This study examined (1) the association between weight loss and changes in health-related quality of life (HRQoL) and (2) treatment response heterogeneity among patients in a weight loss intervention. METHODS: Eighteen primary care clinics were randomized to a 24-month intensive lifestyle intervention or usual care. Generic HRQoL and weight-related QoL were assessed at baseline and months 6, 12, and 24. Associations were analyzed using repeated-measures linear multilevel models. RESULTS: The sample included 803 patients with obesity. Changes in generic HRQoL did not differ by race or sex, and weight-related QoL did not differ by sex. However, Black patients experienced less improvement in weight-related QoL compared to other races. There was a graded association between improvements in weight-related QoL and greater weight loss between baseline and 24 months: 7.4 (95% CI: 5.1, 9.7) for those who lost < 5% of their initial body weight, 15.0 (11.4, 18.5) for 5% to < 10% weight loss, and 18.9 (15.4, 22.4) for ≥ 10% weight loss. Greater weight loss was also related to greater improvements in most generic HRQoL domains. CONCLUSIONS: Weight loss was associated with improvements in HRQoL, and race differences were identified in changes in weight-related QoL, highlighting the need for precision medicine approaches to weight loss. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02561221.
OBJECTIVE: The shift from overweight to obesity predominance and the parallel rise in severe obesity among youth remain insufficiently characterized. This study examines the timing and pattern of this "Obesity-Overweight...OBJECTIVE: The shift from overweight to obesity predominance and the parallel rise in severe obesity among youth remain insufficiently characterized. This study examines the timing and pattern of this "Obesity-Overweight Reversal" in China. METHODS: We analyzed individual-level data from six cycles (1995-2019) of the Chinese National Survey on Students' Constitution and Health. Trends and projections to 2030 were estimated using multinomial logistic regression. Associations between severe obesity and Human Development Index (HDI) were assessed using generalized additive models. RESULTS: From 1995 to 2019, BMI z-score distributions shifted rightward and broadened across demographic groups. Obesity-Overweight Reversal first appeared among urban boys in Tianjin by 2010 and expanded to additional provinces, particularly among boys in the Northeast. Severe obesity rose sharply, reaching 7.66% in Shandong boys in 2019; among girls, severe obesity remained lower but was projected to surpass 5% in the Northeast in 2030. The HDI-severe obesity associations were nonlinear, with a plateau at very high HDI. CONCLUSIONS: China has entered a turning point in the pediatric obesity epidemic since 2010. Pronounced subnational and sex-residence disparities point to the need for context-specific interventions. Monitoring BMI distribution shifts, severe obesity trends, and socioeconomic correlates is essential to inform prevention strategies.
Kasahara K, Okada H, Ide H
… +11 more, Nakajima H, Ushigome E, Nakanishi N, Hamaguchi M, Kurogi K, Murata H, Tsuda E, Yoshida N, Ito M, Furui Y, Fukui M
OBJECTIVE: The national Specific Health Checkups and Guidance program set a "2 cm waist circumference (WC) and 2 kg body weight (BW) reduction" (2cm2kg) target in Japan. This study aimed to examine the validity of the 2c...OBJECTIVE: The national Specific Health Checkups and Guidance program set a "2 cm waist circumference (WC) and 2 kg body weight (BW) reduction" (2cm2kg) target in Japan. This study aimed to examine the validity of the 2cm2kg target. METHODS: We analyzed data from the Panasonic cohort study of adults ≥ 40 years undergoing health checkups in 2020. Anthropometrics, glucose, blood pressure (BP), lipids, and liver function were measured at baseline and 1 year. Achievement of 2cm2kg was defined as ≥ 2 cm WC and ≥ 2 kg BW reductions. Analyses included covariance, logistic regression, spline, and receiver operating characteristic analyses. RESULTS: Among 30,240 participants, the aim of 2cm2kg achieved reductions of over 5 cm in WC and 5 kg in BW. This was significantly associated with improvements in multiple metabolic indicators-including triglycerides, low-density lipoprotein cholesterol, BP, liver function, and high-density lipoprotein cholesterol (all p < 0.0001). Greater reductions in WC and BW yielded larger, consistent benefits across subgroups by sex, age ≥ 50, and baseline medication use. Cutoff values predicting metabolic improvements were generally -1 to -2 cm WC and -1 to -2 kg BW, and spline analyses showed monotonic improvements with greater WC and BW reductions. CONCLUSIONS: Reductions ≥ 2cm2kg were associated with metabolic improvements in Specific Health Checkups and Guidance-eligible individuals.
Mallette JH, Speed JS, Lirette ST
… +2 more, Moore D, Clemmer JS
Obesity (Silver Spring)
· 2026 Apr · PMID 41919489
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OBJECTIVE: This study examined racial differences in weight loss and clinical response to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity using real-world data. METHODS: We retrospect...OBJECTIVE: This study examined racial differences in weight loss and clinical response to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity using real-world data. METHODS: We retrospectively analyzed our institution's Research Data Warehouse (RDW) containing deidentified data from electronic health records (EHRs) from adults aged 18 years and older. EHR data from the University of Mississippi Medical Center RDW were analyzed for 7214 adults (2182 White; 5032 Black) prescribed injectable GLP-1RA between 2015 and 2025. Inclusion criteria were BMI ≥ 30 kg/m and ≥ 1 GLP-1RA. Longitudinal changes in patient data were modeled using generalized additive mixed models. RESULTS: At 2.5 years, White individuals experienced significantly greater body weight loss than Black individuals: -7.1% (95% CI -8.0%, -6.2%) versus -4.9% (95% CI -5.4%, -4.3%), as well as significantly larger reductions in estimated glomerular filtration rate, systolic blood pressure, and HbA1c. Semaglutide and tirzepatide were associated with the greatest improvements. Renal function decline was attenuated in both groups after therapy. CONCLUSIONS: In a large, diverse EHR cohort, GLP-1RA therapy was associated with significant weight, glycemic, and renal benefits that were attenuated in Black adults. These findings highlight the urgent need to understand mechanisms contributing to variable GLP-1RA outcomes among different populations.
Nagata JM, Frimpong I, Nguyen ND
… +9 more, Heuer A, Helmer CK, Al-Shoaibi AA, Ganson KT, Testa A, Dooley EE, Gabriel KP, Baker FC, Gooding HC
Obesity (Silver Spring)
· 2026 May · PMID 41916773
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OBJECTIVE: This study aimed to prospectively identify the independent, mutually adjusted, and interactive associations of screen time and physical activity with BMI and overweight/obesity risk in adolescents. METHODS: Th...OBJECTIVE: This study aimed to prospectively identify the independent, mutually adjusted, and interactive associations of screen time and physical activity with BMI and overweight/obesity risk in adolescents. METHODS: This study analyzed prospective data from 5356 US adolescents in the Adolescent Brain Cognitive Development (ABCD) Study, Year 2 (2018-2020, ages 11-12) and Year 4 (2020-2022, ages 13-14). RESULTS: Mean daily screen time was 6.1 (±5.2) hours and mean step count was 9265 (±3227) steps in Year 2; 32.7% were classified with overweight/obesity in Year 4. In Poisson regression models examining the exposures mutually adjusted for each other, high screen time (> 8 h/day) was associated with higher risk of overweight/obesity (risk ratio [RR], 1.09; 95% CI, 1.02-1.16; p = 0.013) compared with low screen time (0-4 h/day). In multivariable linear and Poisson regression models, respectively, low step count (1000-6000 steps/day) was associated with higher BMI percentile (coefficient [B], 3.27; 95% CI, 1.54-4.99; p < 0.001) and higher risk of overweight/obesity (RR, 1.23; 95% CI, 1.07-1.40; p = 0.003) compared with high step count (> 12,000 steps/day). No significant interactions were observed between screen time and step count. CONCLUSIONS: These findings suggest that obesity prevention efforts should consider both greater physical activity and less recreational screen use as behavioral interventions.
Tronieri JS, Kushner RF, Apovian CM
… +3 more, Fitch A, Still C, Wadden TA
Obesity (Silver Spring)
· 2026 May · PMID 41914839
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OBJECTIVE: The present study examined the safety and efficacy of the fixed-dose, extended-release combination of naltrexone and bupropion (NB-ER) in individuals with overweight/obesity and mild to moderate symptoms of de...OBJECTIVE: The present study examined the safety and efficacy of the fixed-dose, extended-release combination of naltrexone and bupropion (NB-ER) in individuals with overweight/obesity and mild to moderate symptoms of depression. METHODS: Data were pooled from four double-blind, placebo-controlled trials. Participants with baseline Inventory of Depressive Symptomatology-Self-Report scores ≥ 14 suggestive of mild or greater depressive symptoms were included (N = 511). Primary outcomes were 56-week percent weight loss and changes in depression, as well as safety data for psychiatric adverse events (PAEs), depressive symptom increases, and suicidal ideation. Multiple imputation was applied, and outcomes were compared in the intention-to-treat population. RESULTS: In participants with symptoms of depression, 56-week weight loss was significantly greater with NB-ER (5.7% ± 0.6%) than with placebo (2.7% ± 0.8%; p = 0.003). Participants experienced clinically meaningful improvements in depression of -7.1 ± 0.4 with NB-ER and -6.7 ± 0.5 with placebo, with no significant differences between the groups. NB-ER and placebo did not differ in safety signals including PAE occurrence (27.5% NB-ER vs. 22.1% placebo), depressive symptom increases (9.5% NB-ER vs. 8.8% placebo), or suicidal ideation (1.8% NB-ER vs. 2.0% placebo). CONCLUSIONS: NB-ER appears to be both safe and effective for weight loss when offered to patients with mild to moderate symptoms of depression.
Ostberg JE, Ahmed Z, Saatchi K
… +4 more, Pandher PK, Rahim Y, Häfeli UO, Gray SL
Obesity (Silver Spring)
· 2026 May · PMID 41914648
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OBJECTIVE: This study aimed to assess iron oxide magnetic nanoparticles (MNPs) for adipose tissue-targeted therapeutics to restore adipose tissue function and insulin sensitivity in obesity. METHODS: The insulin-sensitiz...OBJECTIVE: This study aimed to assess iron oxide magnetic nanoparticles (MNPs) for adipose tissue-targeted therapeutics to restore adipose tissue function and insulin sensitivity in obesity. METHODS: The insulin-sensitizing effects of rosiglitazone and known adverse effects were leveraged for this proof-of-concept assessment of adipose tissue drug targeting. Rosiglitazone was adsorbed to alendronic acid-coated MNPs (rosiMNPs) and a biocompatible magnet implanted in the right inguinal white adipose tissue (ingWAT) of obese, insulin resistant male mice. Following rosiMNP treatment (1.5 mg/kg/day, 18 days), insulin sensitivity and adipose tissue health were assessed. RESULTS: RosiMNPs restored insulin sensitivity as well as systemic rosiglitazone (1.5 mg/kg/day, 18 days), with a shift in adipocyte size compatible with PPARγ-induced adipocyte hyperplasia and no increase in circulating adiponectin. PPARγ target genes were induced in ingWAT with rosiMNPs or systemic rosiglitazone, but only in liver and gonadal WAT of systemically treated mice. Additionally, iron accumulation was shown in the right, targeted ingWAT depot, but not in the left, untargeted ingWAT, kidney, or liver, suggesting targeting was achieved. Unfortunately, the dose and duration of systemic treatment were ineffective at inducing changes in kidney. CONCLUSIONS: Results demonstrate the potential benefits of adipose tissue-targeted therapeutics to improve adipose tissue function to restore insulin sensitivity to prevent the metabolic complications of obesity.
OBJECTIVE: This study compared weight-loss outcomes in patients prescribed tirzepatide by weight-loss status and assessed results among patients transitioning from semaglutide. METHODS: This retrospective cohort study an...OBJECTIVE: This study compared weight-loss outcomes in patients prescribed tirzepatide by weight-loss status and assessed results among patients transitioning from semaglutide. METHODS: This retrospective cohort study analyzed 6-month weight-loss outcomes in adults treated with tirzepatide between May 2022 and January 2023. Patients were classified as weight-reduced if they had lost ≥ 10% total body weight (TBW) before starting tirzepatide. Among those who switched from therapeutic semaglutide (≥ 1.7 mg weekly for ≥ 1 month), reasons for switching were categorized as non-response (< 5% weight loss after ≥ 3 months), plateau (≥ 5% loss followed by weight stabilization), or other. RESULTS: Of 941 charts, 293 (31.1%) met inclusion criteria (65% female; mean age 52 years; mean BMI 36.15 kg/m). Weight-reduced patients (n = 133) lost 7.2% TBW versus 10.3% in non-weight-reduced patients (n = 160; p < 0.001). When analyses were stratified by type 2 diabetes (T2D) status, this difference remained significant among patients without T2D. Sixty-one patients switched from semaglutide due to non-response or plateau and lost 5.3% TBW. Those switching at a plateau (n = 28) lost 8.1% versus 2.9% for non-responders (n = 33; p < 0.001). CONCLUSIONS: Tirzepatide produced meaningful weight loss across groups but outcomes varied based on weight-reduction status, T2D status, and prior response to semaglutide.
Heart failure with preserved ejection fraction (HFpEF) now represents the dominant form of heart failure in the United States. Approximately 80% of HFpEF patients also live with obesity. This review highlights the centra...Heart failure with preserved ejection fraction (HFpEF) now represents the dominant form of heart failure in the United States. Approximately 80% of HFpEF patients also live with obesity. This review highlights the central role of obesity in driving the pathophysiology and clinical presentation of HFpEF, particularly exercise intolerance, which is the hallmark symptom of heart failure. We summarize evidence that obesity promotes early concentric remodeling, diastolic dysfunction, and atrial enlargement while reducing the diagnostic utility of natriuretic peptides. We also examine how cardiopulmonary exercise testing (CPET), the gold standard for assessing exercise capacity, reveals obesity-related impairments in peak oxygen uptake, chronotropic response, and pulmonary pressures. Beyond cardiac contributions, obesity amplifies peripheral drivers of exercise intolerance, including vascular stiffening, endothelial dysfunction, impaired skeletal muscle oxygen utilization, mitochondrial dysfunction, and myosteatosis. We also discuss new evidence that the chronic inflammatory response can drive central and peripheral dysfunction (systemic fibrosis and skeletal muscle atrophy) to reduce functional capacity in HFpEF. Together, these findings position obesity as a central, modifiable determinant of HFpEF and underscore the need for mechanistic studies targeting skeletal muscle, vascular, and inflammatory pathways.
Duran-Bertran J, Clavero-Mestres H, Mahmoudian R
… +9 more, Muñiz-Piera S, Aguilar C, Riesco D, Camaron J, Martínez S, Vives M, París M, Sabench F, Auguet T
Obesity (Silver Spring)
· 2026 May · PMID 41885053
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OBJECTIVE: This study aimed to investigate the platelet-activating factor (PAF) pathway in obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD) by evaluating hepatic expression of the PAF r...OBJECTIVE: This study aimed to investigate the platelet-activating factor (PAF) pathway in obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD) by evaluating hepatic expression of the PAF receptor (PAFR) and circulating levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) across different stages of disease severity. METHODS: Liver biopsies and blood samples were collected from 64 women with severe obesity undergoing bariatric surgery. Hepatic PAFR mRNA expression was quantified by qRT-PCR, and plasma Lp-PLA2 concentrations were measured using ELISA. Histological evaluation of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) was performed according to established criteria. Associations between biochemical, histological, and molecular parameters were analyzed using appropriate statistical tests. RESULTS: Hepatic PAFR expression was significantly upregulated in MASLD, with the highest levels observed in patients with MASH. PAFR expression correlated positively with key histological features, including steatosis, lobular inflammation, and hepatocyte ballooning. In contrast, circulating Lp-PLA2 levels did not differ across MASLD stages and showed no correlation with hepatic PAFR expression or with liver injury markers. CONCLUSIONS: The PAF-PAFR axis is upregulated in obesity-associated MASLD and is strongly linked to inflammatory and injury-related histological features, supporting PAFR as a potential therapeutic target. Conversely, plasma Lp-PLA2 does not appear to be a reliable noninvasive biomarker of MASLD severity in women with obesity.
OBJECTIVE: Obesity is associated with the risk of several cancers, yet conventional anthropometric measures do not distinguish the contributions of different compartments of abdominal adipose tissue. This study examined...OBJECTIVE: Obesity is associated with the risk of several cancers, yet conventional anthropometric measures do not distinguish the contributions of different compartments of abdominal adipose tissue. This study examined the relationship between visceral (VAT) and subcutaneous (SAT) abdominal adiposity and the incidence of 13 obesity-related cancers (ObRCs) in postmenopausal women. METHODS: Data from 9950 postmenopausal participants in the Women's Health Initiative (WHI) dual-energy X-ray absorptiometry (DXA) cohort were analyzed. Abdominal VAT and SAT were quantified from DXA scans using validated imaging software. Fine and Gray competing-risks models estimated associations with ObRC incidence over 177,295 person-years of follow-up. RESULTS: Higher abdominal VAT was significantly associated with higher ObRC risk, independently of BMI, waist circumference (WC), and other confounders. Each 100-cm increase in VAT corresponded to a 32% higher risk, with a nearly twofold increase for women in the highest VAT quartile. SAT and the VAT/SAT ratio were also significantly associated with risk, though more modestly. Findings were consistent across BMI, WC, age, and race/ethnicity strata and in time-varying models. CONCLUSIONS: Visceral adiposity has a strong, independent association with ObRC risk in postmenopausal women. Incorporating imaging-based body composition measures may improve cancer risk stratification and guide targeted prevention strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.
OBJECTIVE: This study examined the safety and effectiveness of metabolic and bariatric procedures (MBPs), including surgical and endoscopic interventions, among individuals with versus without heart failure (HF). METHODS...OBJECTIVE: This study examined the safety and effectiveness of metabolic and bariatric procedures (MBPs), including surgical and endoscopic interventions, among individuals with versus without heart failure (HF). METHODS: This multicenter retrospective cohort study (2021-2023) identified persons with HF who underwent MBPs at two medical centers. Thirty-day safety events and changes in body weight and medication use were assessed. RESULTS: Of 1678 MBPs, 41 (2.4%) were performed in adults with HF (mean age, 51 ± 15 years; 66% female; mean BMI, 44 ± 7 kg/m). Despite older age and more obesity-related complications, persons with HF did not appear to experience a higher risk of any safety event at 30 days versus those without HF (24% vs. 16%; adjusted OR, 1.64; 95% CI, 0.76-3.58; p = 0.21). Thirty-day change in body weight was similar between those with (-5.9%; 95% CI, -6.9%, -4.9%) and without HF (-6.2%; 95% CI, -6.4%, -6.0%; p = 0.57). By 1 year, individuals with HF experienced significant reductions in body weight (mean change, -18.7%; 95% CI, -22.1%, -15.3%; p < 0.001), cardiovascular (p = 0.003) and glucose-lowering medications (p < 0.001), and loop diuretics (p = 0.003). CONCLUSIONS: These findings suggest that MBPs are safe and effective in well-selected adults with obesity and HF. However, larger and prospective studies are warranted to enhance understanding of MBP risk/benefit in this population.
Alkwatli K, Xiao H, Mariam-Smith A
… +5 more, Lopetegui N, Griebeler ML, Burguera B, Pantalone KM, Rotroff DM
Obesity (Silver Spring)
· 2026 Apr · PMID 41806301
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OBJECTIVE: Obesity is a major risk factor for multiple cancers, yet the impact of nonsurgical weight loss on cancer risk remains uncertain. Our objective was to evaluate whether real-world nonsurgical weight loss is asso...OBJECTIVE: Obesity is a major risk factor for multiple cancers, yet the impact of nonsurgical weight loss on cancer risk remains uncertain. Our objective was to evaluate whether real-world nonsurgical weight loss is associated with a reduced risk of developing cancer. METHODS: We conducted a retrospective observational study of 143,630 adults (BMI ≥ 30) from an integrated US health system's electronic health records (2000-2022). Cases with incident cancer were compared to matched controls. Using generalized linear models with a logit link, we assessed whether BMI change over 3-, 5-, and 10-year intervals is associated with the risk of diagnosis for obesity-related and other cancers. RESULTS: Among 143,630 patients, 7703 cases and 135,927 controls were identified. Each 1% BMI reduction was linked to lower obesity-related cancer risk at 3 years (OR, 0.990; 95% CI, 0.984-0.996; p < 0.001), 5 years (OR, 0.989; 95% CI, 0.984-0.995; p < 0.001), and 10 years (OR, 0.992; 95% CI, 0.984-1.000; p = 0.057). Similar associations were observed for other cancer types across all intervals (OR < 1; p < 0.001). CONCLUSIONS: Real-world weight loss was associated with a decreased risk of obesity-related and other cancers.
OBJECTIVE: HDM1002, a small-molecule agonist of glucagon-like peptide-1 receptors, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). METHODS: Chinese participants (18-60 years) wit...OBJECTIVE: HDM1002, a small-molecule agonist of glucagon-like peptide-1 receptors, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). METHODS: Chinese participants (18-60 years) with BMI ≥ 24.0 kg/m to ≤ 36.0 kg/m without diabetes were enrolled and randomized 5:1 (12 per cohort) to receive HDM1002 or placebo orally for 28 days. Dose cohorts included 50 mg once daily (QD); 100 mg QD; 200 mg QD; 100 mg twice daily (BID); and 400 mg QD. Primary endpoint was safety, assessed by treatment-emergent adverse events (TEAEs), vital signs, physical examination, electrocardiogram, and laboratory parameters. Secondary endpoints were PK/PD analyses. RESULTS: TEAEs in 50/100/200 mg QD, 100 mg BID, and 400 mg QD HDM1002 groups were 80%, 70%, 100%, 90%, and 100%, respectively, and 60% in the placebo group, all mild/moderate. Two participants discontinued HDM1002 due to TEAEs versus none in the placebo group. Greater least squares mean reductions from baseline in body weight were among HDM1002 200 mg QD (-6.1 kg), 100 mg BID (-4.4 kg), and 400 mg QD (-4.3 kg) groups, compared with placebo (-1.6 kg). There was no significant effect on glycemia observed with HDM1002 compared to placebo. PK were generally doseproportional. CONCLUSIONS: HDM1002 demonstrated a manageable safety/tolerability profile. TRIAL REGISTRATION: CTR20233390.
OBJECTIVE: This study aimed to assess the spectrum and frequency of adverse events (AEs) linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) using the US FDA Adverse Event Reporting System (FAERS). Emphasis wa...OBJECTIVE: This study aimed to assess the spectrum and frequency of adverse events (AEs) linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) using the US FDA Adverse Event Reporting System (FAERS). Emphasis was placed on emerging safety concerns in context-specific use. METHODS: A retrospective analysis of FAERS reports between 2012 and 2025 was conducted. Five commonly prescribed FDA-approved GLP-1RAs were included. Disproportionality analyses were applied to detect AE signals. Subgroup analyses evaluated associations by indication, GLP-1RAs compared to other drugs, and AEs specific to individual GLP-1RAs. RESULTS: From over 18 million FAERS reports, 137,451 involved GLP-1RAs. The most frequent AEs were gastrointestinal, nutritional and metabolic, and psychiatric disorders, occurring at higher rates compared to other drugs. In diabetes use, GLP-1RAs were associated with retinopathy, hearing loss, and cataracts. In contrast, when prescribed for weight management/obesity, nutritional, metabolic, and psychiatric AEs predominated. We also developed an open-access portal for AE exploration, available at http://glp1.tanlab.org. CONCLUSIONS: GLP-1RAs are linked to a broad range of AEs across indications. These findings stress the need for careful clinical monitoring and long-term safety evaluation. This study also illustrates how real-world evidence can inform safety communications, as well as hypothesis generation for research on next-generation GLP-1RAs.