Heeren FAN, Ruddiman KR, Simmons C
… +10 more, White BN, Jaeger BC, Pajewski NM, Hooker SA, Horn DB, Martin-Fernandez K, Gudzune KA, Young CB, Ard J, Lewis KH
Obesity (Silver Spring)
· 2026 Jan · PMID 41145317
·
Full text
OBJECTIVE: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status. METHODS: The crit...OBJECTIVE: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status. METHODS: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity." RESULTS: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m [SD 3.5]), and 80.5% had clinical obesity (mean BMI 35.9 kg/m [SD 4.3]). Participants with no/pre-clinical obesity had lower mean SF-12 mental component scores and greater baseline engagement with weight control strategies compared to those with clinical obesity. Participants with clinical obesity were older and, by definition, had a greater burden of cardiometabolic risk factors. CONCLUSIONS: Among clinical trial participants eligible for obesity pharmacotherapy, 19.5% were classified as having no/pre-clinical obesity using the Lancet criteria. Applying the criteria was complicated in a well-resourced trial setting, which suggests potential challenges in implementing these guidelines in real-world practice.
Fennel ZJ, Kurian AS, Bourrant PE
… +9 more, Skiles CM, Castro RJ, Yee EM, Greilach SA, Keirstead HS, Nistor G, Berchtold NC, Lane TE, Drummond MJ
Obesity (Silver Spring)
· 2026 Feb · PMID 41140016
·
Full text
OBJECTIVE: In this study, we investigated the effects of a stem cell-derived secretome product on adiposity and tissue quality and insulin and glucose levels in obese mice and those undergoing dietary weight loss. METHOD...OBJECTIVE: In this study, we investigated the effects of a stem cell-derived secretome product on adiposity and tissue quality and insulin and glucose levels in obese mice and those undergoing dietary weight loss. METHODS: Following 16 weeks of high fat diet mice received acute (4 weeks) biweekly intramuscular injections with vehicle or secretome while remaining on a high fat diet (HFD vs. HFD-S) or during weight loss upon return to a normal chow diet (HFD/WL vs. HFD/WL-S). RESULTS: After 4 weeks of treatment, HFD-S mice had greater lean mass (vs HFD), muscle weights, and quadriceps myofibrillar size and improved muscle quality (capillary density and fibrosis). HFD/WL-S mice had accelerated whole-body fat loss and improved glucose handling, fasting insulin levels, and HOMA-IR. In both secretome-treated groups (HFD-S and HFD/WL-S), liver steatosis and fibrosis were improved and similar to chow controls. CONCLUSIONS: Together, these results support that a stem cell secretome treatment may be useful to improve tissue quality and metabolic health during obesity and weight loss.
OBJECTIVE: Behavioral sleep interventions may have lasting impacts on sleep and health and serve as a novel obesity prevention strategy. We explored effects of an online infant sleep intervention on sleep, weight status,...OBJECTIVE: Behavioral sleep interventions may have lasting impacts on sleep and health and serve as a novel obesity prevention strategy. We explored effects of an online infant sleep intervention on sleep, weight status, and weight-related behaviors (e.g., diet) into toddlerhood. METHODS: First-time parents or legal guardians ≥ 18 years old were recruited when their infant was < 6 weeks old and randomized (block size 2, 1:1 allocation ratio) to a sleep intervention (n = 36) or baby care control group (n = 38). The intervention was delivered weekly via private online groups when infants were 2-4 months old. Participants completed surveys at baseline (infant age 6 weeks), midpoint (3 months), post-intervention (4 months), and infant follow-up (7 months). Participants also completed a toddler follow-up survey (mean age = 20.7 months; n = 67) assessing behaviors and weight/length. RESULTS: By toddlerhood, the intervention group slept longer (12.99 ± 2.03 vs. 11.94 ± 2.06 h per day, p = 0.049) and had lower weight-for-length z-scores (0.62 ± 1.34 vs. 1.33 ± 1.35, p = 0.04) than controls. CONCLUSIONS: Results support early sleep interventions as a novel and promising approach to childhood obesity prevention and demonstrate the feasibility of online intervention delivery. Future research should further examine mechanisms and confirm findings using objective weight status measures. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05322174.
Shearer J, Scantlebury MH, Erome-Utunedi O
… +5 more, Choudhary A, Thompson JA, Ohland C, McCoy KD, Mu C
Obesity (Silver Spring)
· 2026 Feb · PMID 41140006
·
Full text
OBJECTIVE: Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiol...OBJECTIVE: Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of Asic1a influences obesity, metabolic, and gut-based outcomes. METHODS: Employing male and female rats with systemic Asic1a deletion (Asic1a ), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high-fat diet administration for 8 weeks. Fecal microbiota transplantation into germ-free mice was carried out as a proof-of-concept approach to assess the gut microbiota's direct impact. RESULTS: On a chow diet, Asic1a deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild-type controls. These effects were exacerbated with high-fat diet administration. Asic1a reshaped the gut microbiota, characterized by the enrichment of Bacteroides and Akkermansia. Microbiota transplantation from Asic1a rats to recipient germ-free mice increased body weight gain relative to those from wild-type rats, implicating the potential role of gut microbiota. CONCLUSIONS: Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.
Descamps-Solà M, Jalševac F, Vilalta A
… +9 more, Fontcuberta M, Park H, Aguilar C, Auguet T, Beltrán-Debón R, Rodríguez-Gallego E, Pinent M, Terra X, Ardévol A
Obesity (Silver Spring)
· 2026 Jan · PMID 41140001
·
Full text
OBJECTIVE: Obesity is a chronic disease with various causes and diverse treatments, including dietary restriction and bariatric surgery. Bitter taste receptors (TAS2Rs), found in the oral cavity and gastrointestinal trac...OBJECTIVE: Obesity is a chronic disease with various causes and diverse treatments, including dietary restriction and bariatric surgery. Bitter taste receptors (TAS2Rs), found in the oral cavity and gastrointestinal tract (GIT), are implicated in digestive and metabolic regulation, but their role in obesity remains unclear. This study investigates intestinal TAS2R expression concerning obesity and bariatric surgery outcomes. METHODS: TASas2r expression was assessed in intestinal segments of female rats fed a cafeteria diet for 17 weeks. Additionally, jejunal TAS2R expression was measured in women with class III obesity, with or without metabolic syndrome (MS), undergoing Roux-en-Y gastric bypass (RYGB). Associations with weight loss at 12 months postsurgery were evaluated. RESULTS: In rats, cafeteria diet significantly reduced Tas2r expression, especially in the jejunum and duodenum. In women with MS, higher expression of TAS2R13 and TAS2R20 correlated with greater weight loss post-after RYGB. In those without metabolic syndrome, higher TAS2R5 expression showed similar associations. TAS2R expression was strongly linked to surgical outcomes. In rats, Tas2r108 (ileum) and Tas2r144 (jejunum) expression levels differed between obese and lean animals. CONCLUSIONS: Intestinal TAS2Rs may influence metabolic regulation and bariatric surgery outcomes, suggesting their potential as therapeutic targets in female obesity. Further studies should clarify their underlying mechanisms.
OBJECTIVE: Individuals with obesity often struggle to resist the temptation of palatable food, which may be linked to impaired inhibitory control-a crucial cognitive function for regulating eating behavior. Enhancing inh...OBJECTIVE: Individuals with obesity often struggle to resist the temptation of palatable food, which may be linked to impaired inhibitory control-a crucial cognitive function for regulating eating behavior. Enhancing inhibitory control over food-related memories has been proposed as a potential intervention strategy for obesity. The right dorsolateral prefrontal cortex (dlPFC) plays a key role in regulating reward-driven impulses. However, it remains unclear whether neuromodulating the right dlPFC can selectively strengthen inhibitory control over food-related memories, particularly in individuals with overweight/obesity status who exhibit heightened reward sensitivity and diminished executive function. METHODS: This study employed a food Think/No-Think (TNT) training combined with HD-tDCS targeting the right dlPFC to assess its effects on inhibitory control over food-related memory in individuals with overweight/obesity. RESULTS: Both groups with healthy weight and overweight/obesity demonstrated significant improvements in memory suppression following anodal stimulation. Notably, individuals with overweight/obesity exhibited greater reductions in memory intrusion at the early stage, suggesting they may benefit more from anodal stimulation in resisting memory intrusions. CONCLUSIONS: These findings highlight the potential of combining neuromodulation with cognitive training as a promising intervention for obesity, providing both theoretical insights and empirical evidence for future prevention and treatment approaches.
OBJECTIVE: This study investigated the neural mechanisms underlying appetite dysregulation in female subjects with abdominal obesity (AO) by identifying functional connectivity (FC) and network-level differences between...OBJECTIVE: This study investigated the neural mechanisms underlying appetite dysregulation in female subjects with abdominal obesity (AO) by identifying functional connectivity (FC) and network-level differences between moderate appetite (MA) and strong appetite (SA) subtypes. METHODS: A total of 60 women with AO (30 MA, 30 SA) and 30 healthy controls (HCs) underwent resting-state fMRI. Independent component analysis was used to identify and examine FC within and functional network connectivity (FNC) between key resting-state networks, including those involved in cognitive and visual processing. Network alterations and correlations with obesity-related indicators were evaluated. RESULTS: Compared to HCs, both groups showed reduced FC in the default mode network (DMN) and visual network (VN), with SA additionally exhibiting decreased FC in the frontoparietal network (FPN) and lower angular gyrus FC than MA (p < 0.05, FDR-corrected). MA displayed increased DMN-left FPN (FPN_L) FNC (p < 0.001), while SA showed negative correlations between FC and BMI/appetite visual analog scale (VAS) scores in FPN and with body weight/BMI/appetite VAS in VN (p < 0.05). In HCs, DMN-FPN_L FNC positively correlated with BMI, a pattern that was not observed in MA. CONCLUSION: Distinct brain network patterns characterize appetite subtypes in AO. SA showed more pronounced FC reductions in networks previously linked to self-regulation and visual processing, which may contribute to appetite dysregulation based on correlations with obesity indicators. In contrast, MA exhibited increased DMN-FPN_L FNC, potentially reflecting adaptive internetwork interactions.
Andreyeva E, Graham ML, Eldridge GD
… +4 more, Folta SC, Nelson ME, Strogatz D, Seguin-Fowler RA
Obesity (Silver Spring)
· 2026 Jan · PMID 41102867
·
Full text
OBJECTIVE: This study aimed to conduct cost analysis (CA) and cost-effectiveness analysis (CEA) of Strong Hearts, Healthy Communities (SHHC) implemented in two randomized trials. METHODS: Women with obesity or women who...OBJECTIVE: This study aimed to conduct cost analysis (CA) and cost-effectiveness analysis (CEA) of Strong Hearts, Healthy Communities (SHHC) implemented in two randomized trials. METHODS: Women with obesity or women who were sedentary with overweight who were ≥ 40 years old from rural medically underserved towns were randomized to SHHC intervention or control. CA calculated total and per participant costs and opportunity costs. CEA compared incremental costs to incremental outcome changes. Quality-adjusted life year (QALY) CEA compared incremental costs and effectiveness of a national SHHC intervention for a hypothetical cohort of 2.2 million women. RESULTS: SHHC-1.0 resource cost was $775/participant and SHHC-2.0 was $747. The incremental cost-effectiveness ratio from the payer's perspective for SHHC-1.0 was $346/kg weight loss and $187 and $155 for SHHC-2.0 at 24 and 48 weeks, respectively. Over a 10-year horizon, to avert QALYs lost, SHHC-1.0 was estimated to cost $238,271 from the societal perspective and $62,646 from the health care sector perspective. For SHHC-2.0, the corresponding numbers were $214,257 and $67,747 at 24 weeks and $94,395 and $11,341 at 48 weeks. CONCLUSIONS: SHHC-2.0 compared favorably to SHHC-1.0 and could be cost-effective for longer-term effects. Results can help guide policy makers' decisions on larger-scale community-based obesity and cardiovascular disease prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03059472.
Obesity (Silver Spring)
· 2025 Nov · PMID 41102137
·
Full text
OBJECTIVE: This study aimed to estimate population-level effects on weight change of initiating/adhering to additional glucose-lowering medications in adults with type 2 diabetes prescribed metformin. METHODS: We conduct...OBJECTIVE: This study aimed to estimate population-level effects on weight change of initiating/adhering to additional glucose-lowering medications in adults with type 2 diabetes prescribed metformin. METHODS: We conducted a target trial using electronic health record data from 22,601 patients (age 20 to < 80 years) prescribed metformin to determine initiation/adherence to dipeptidyl peptidase IV (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, long-acting insulin, or sulfonylureas. Inverse probability weighting of marginal structural models with standardization by baseline covariates was used to estimate population-level effects of initiating/adhering to different medications on average 24-month weight change. RESULTS: At 24 months, a mean -5.15 kg (95% CI -10.6, -1.36) and -6.71 kg (95% CI -8.38, -4.34) weight loss would be observed for initiation/adherence to GLP-1RAs and SGLT-2s respectively. At 6 months, weight loss for DPP4s would be observed (-0.89 kg, 95% CI -1.41, -0.32) though not at 12 or 24 months. Glimepiride would be associated with weight gain at 6 and 12 months (0.88 kg, 95% CI 0.44, 1.22; 1.01 kg, 95% CI 0.32, 1.51) but not at 24 months. CONCLUSIONS: Initiation/adherence to GLP-1RAs and SGLT-2s over 24 months could result in average weight losses of 5.15 kg and 6.71 kg, respectively.
Byrne JP, Hinton EC, Humayun AM
… +7 more, Pournaras DJ, Elsworth RL, Brunstrom JM, Hamilton-Shield JP, Sumeray M, Easter C, Ashrafian H
Obesity (Silver Spring)
· 2026 Jan · PMID 41090617
·
Full text
OBJECTIVE: This study investigated the safety, tolerability, and preliminary efficacy of Sirona, a novel gastro-retentive, dual-network polymer for weight management. METHODS: This pilot trial comprised a randomized, par...OBJECTIVE: This study investigated the safety, tolerability, and preliminary efficacy of Sirona, a novel gastro-retentive, dual-network polymer for weight management. METHODS: This pilot trial comprised a randomized, parallel-group, double-blind, placebo-controlled (3:1 ratio), 12-week period, with a 12-week open-label extension (OLE), in participants with BMI of 30-40 kg/m. Primary endpoints were feasibility, tolerability, and safety; secondary endpoints included weight loss and dietary intake, tested using Hedge's g [95% CI] as a measure of effect size. RESULTS: Participants received Sirona (n = 29/38) or Placebo (n = 9/38) (mean [SD] age = 40.9 [8.4]; weight = 101.7 [12.9] kg; BMI = 35.6 [3.0]; 29/38 female and 23/38 White British). Dosing was well tolerated (RCT Sirona: 95.2 [11.0]%; RCT Placebo: 97.8 [3.5]%; RCT + OLE Sirona: 93.1 [13.0]%). No serious adverse events occurred. Of the adverse events, nausea was most prominent (74.8%), mostly graded mild (79.3%) and requiring no intervention (84.4%). Percentage total body weight loss was greater for Sirona compared to Placebo after 12 weeks (3.9 [3.0]% versus 1.0 [2.1]%, g = 0.96 [-1.81, -0.10]). Weight loss continued in the OLE (change from baseline = 4.4 [3.8]%). Dietary intake reduced from baseline after 12 weeks of treatment (-382.5 [519.3] kcal; Placebo = 93.5 [670.3] kcal, g = -0.8 [-1.7, 0.0]) and after 24 weeks (-338.2 [486.7] kcal, g = 0.7 [0.2, 1.1]). CONCLUSIONS: Sirona was well tolerated, with mild, primarily gastrointestinal side effects. Reduced weight and dietary intake suggest Sirona is suitable as a nonpharmacological treatment for weight management. TRIAL REGISTRATION: ISRCTN14083641 (https://doi.org/10.1186/ISRCTN14083641).
Dadson P, Honka MJ, Suomi T
… +8 more, Rokka A, Kauhanen S, Salminen P, Helmiö M, James P, Elo LL, Olkkonen VM, Nuutila P
Obesity (Silver Spring)
· 2026 Jan · PMID 41077621
·
Full text
OBJECTIVE: Severe obesity poses a major public health concern due to its links with cardiometabolic complications and mortality. Visceral adipose tissue (VAT) plays a key role in these processes through distinct molecula...OBJECTIVE: Severe obesity poses a major public health concern due to its links with cardiometabolic complications and mortality. Visceral adipose tissue (VAT) plays a key role in these processes through distinct molecular features. This study aimed to characterize the VAT proteome of individuals with severe obesity and investigate its association with serum metabolic biomarkers. METHODS: A cross-sectional analysis was performed for 46 individuals with severe obesity undergoing metabolic bariatric surgery and 17 healthy controls undergoing elective abdominal surgery. VAT proteomes were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and serum metabolites were quantified using nuclear magnetic resonance-based metabolomics. RESULTS: LC-MS/MS identified 22 differentially expressed proteins (FDR < 0.05) in VAT with 12 downregulated and 10 upregulated in severe obesity. Downregulated proteins included mitochondrial enzymes involved in substrate metabolism and mitochondrial transmembrane transport. Circulating glucose, valine, and isoleucine correlated negatively with VAT mitochondrial transmembrane and electron transport proteins. Upregulated proteins were associated with inflammation, immune activation, oxidative stress, cytoskeletal remodeling, and protein turnover. CONCLUSIONS: These findings demonstrate significant molecular alterations in the VAT proteome associated with severe obesity, providing insights into the underlying mechanisms of metabolic disease. The differentially expressed proteins may serve as biomarkers or therapeutic targets for obesity-related complications. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00793143 and NCT01373892.
Legrand MA, Paccou J, Lecerf JM
… +5 more, Thomas T, Chapurlat R, Cortet B, Biver E, Papageorgiou M
Obesity (Silver Spring)
· 2026 Jan · PMID 41070756
·
Full text
Although weight loss has many health benefits for people with overweight/obesity, its potential negative impact on bone health needs to be considered. This review provides a comprehensive overview of the effects of inten...Although weight loss has many health benefits for people with overweight/obesity, its potential negative impact on bone health needs to be considered. This review provides a comprehensive overview of the effects of intentional weight loss achieved by lifestyle changes on bone health outcomes in adults with overweight/obesity and discusses potential mechanisms underlying the observed skeletal effects and protective measures to preserve bone health in this context. Weight loss achieved through lifestyle modifications increases surrogate markers of bone resorption and small but persistent reductions in bone mineral density at clinically relevant sites (mainly at the level of the hip). Based on limited available data, weight loss achieved by lifestyle modifications may increase fragility fractures. Combating sedentary lifestyles and promoting exercise, particularly resistance exercise, adequate intakes of calcium (diets and/or supplements), vitamin D supplementation, and higher dietary protein intakes could attenuate but not fully prevent the increased bone turnover or bone loss often associated with intentional weight loss. Further research needs to explore the skeletal effects of pragmatic interventions that match clinical scenarios, verify if changes in bone macro- and/or microstructure translate to an increased fracture risk, and investigate novel/combined strategies to improve bone health due to weight loss.
Obesity (Silver Spring)
· 2025 Nov · PMID 41062431
·
Full text
OBJECTIVE: Obesity affects 42% of older adults, with rates continuing to rise. This a complex condition influenced by non-modifiable as well as modifiable risk factors. The disease can be treated through modifications to...OBJECTIVE: Obesity affects 42% of older adults, with rates continuing to rise. This a complex condition influenced by non-modifiable as well as modifiable risk factors. The disease can be treated through modifications to diet, physical activity, and behavior and more recently through antiobesity medications (AOMs) and surgery. Treatment must be tailored to individual needs due to age-related metabolic and physiological changes. This review aimed to identify the suitability of seven FDA-approved AOMs in the treatment of obesity in older adults. METHODS: A review of AOMs was performed, focusing on their efficacy in weight loss, side effects, and potential health risks in older adults. Studies were selected to later evaluate the overall suitability and safety of these medications. RESULTS: AOMs can improve cardiovascular outcomes, hypertension, hyperlipidemia, metabolic liver disease, obstructive sleep apnea, and chronic kidney disease. Weight loss in older adults using AOMs is associated with an increased risk of sarcopenia. CONCLUSIONS: From a policy standpoint, ensuring coverage of AOMs for older adults is critical, as these medications help reduce obesity-related complications. However, increased participation in clinical trials is urgently needed to study the impact of quality of life and outcomes in older adults.
OBJECTIVE: This study addressed the paucity of data exploring long-term effects of metabolic and bariatric surgery (MBS)-related weight loss on fitness. METHODS: Data from MBS patients (SURG; n = 82) and comparable non-s...OBJECTIVE: This study addressed the paucity of data exploring long-term effects of metabolic and bariatric surgery (MBS)-related weight loss on fitness. METHODS: Data from MBS patients (SURG; n = 82) and comparable non-surgery participants (NSURG; n = 88) were collected from a subset of a prospective trial, the Utah Obesity Study. Fitness was assessed through maximal and submaximal treadmill tests using a modified Bruce protocol. Submaximal exercise tests were performed preceding surgery at baseline and 11.5 years later. A subset (n = 97) of the 170 participants also performed maximal treadmill tests 2 and 6 years after baseline. Weight and BMI were recorded at each visit. Between-group treadmill time comparisons were adjusted for sex and weight. RESULTS: As expected, SURG had lower BMI and weight than NSURG at all follow-up visits (p < 0.0001). Treadmill time, adjusted for sex, baseline treadmill time, and weight over the 11.5-year period, was elevated in surgery compared to non-surgery groups at all follow-up visits (p < 0.01), but the fitness advantage gradually decreased over time. CONCLUSIONS: An initially dramatic fitness benefit achieved with weight loss in MBS patients gradually declined but remained higher than non-surgery counterparts beyond a decade. An emphasis on physical activity may help sustain improved fitness after bariatric surgery.
Obesity (Silver Spring)
· 2025 Dec · PMID 41054320
·
Full text
The presence of excess weight is no longer a distinguishing feature between patients with type 1 diabetes (T1D) and those with type 2 diabetes (T2D). Obesity treatment in patients with T2D improves glycemic control and r...The presence of excess weight is no longer a distinguishing feature between patients with type 1 diabetes (T1D) and those with type 2 diabetes (T2D). Obesity treatment in patients with T2D improves glycemic control and reduces or even eliminates medication burden. Robust evidence and clear guidelines exist to support and direct effective weight management in patients with T2DM. Now, however, rates of obesity in patients with T1D rival those found in the general population, yet little is known about the efficacy, safety, and unique considerations of obesity treatment (lifestyle modifications, pharmacology, and surgery) in this population. This review tackles these topics and the gaps in evidence and clinical care.
OBJECTIVE: To estimate long-term weight change after initiation and adherence to commonly used antiseizure medications (ASMs) and examine differences in weight change across ASMs compared to topiramate. METHODS: We inclu...OBJECTIVE: To estimate long-term weight change after initiation and adherence to commonly used antiseizure medications (ASMs) and examine differences in weight change across ASMs compared to topiramate. METHODS: We included 52,309 adult patients who initiated ASMs, applied a target trial emulation approach to control time-varying confounding and selection bias, and examined the long-term comparative effects on weight change after initiating and adhering to different ASMs at 6 and 12 months post initiation. RESULTS: The most commonly initiated ASM was topiramate (41.2%). In comparison to topiramate, we estimated higher 6-month weight change under initiation and adherence to levetiracetam 0.94 kg (95% CI 0.20, 1.64), lamotrigine 1.44 kg (0.74, 1.99), valproate 2.42 kg (1.71, 2.88), carbamazepine 1.32 kg (0.46, 2.16), and oxcarbazepine 1.74 kg (0.85, 2.71), with similar results at 12 months and in sensitivity and subgroup analyses. These results were driven mostly by weight loss with use of topiramate rather than weight gain with use of other ASMs. Results were similar though attenuated when accounting for medication initiation only. CONCLUSIONS: Topiramate was associated with weight loss at 6 and 12 months under either initiation and subsequent adherence or initiation-only effects; other medications were associated with higher weight change. These results provided important information to help with decision-making regarding ASM initiation.