Obesity is commonly classified by body mass index (≥30 kg/m² obesity; 25–29.9 overweight), with lower cutoffs in some populations. It’s a growing global epidemic affecting over a billion people and driving major health and economic burden. Mechanistically, chronic energy surplus expands adipose tissue and promotes ectopic fat deposition. Adipose tissue acts as an endocrine/immune organ. With weight gain, it shifts toward low-grade inflammation with increased macrophage infiltration, higher pro-inflammatory cytokines/adipokines (eg, higher leptin), and lower adiponectin—setting up metabolic syndrome and insulin resistance.

These changes link obesity to cancer, cardiovascular disease, type 2 diabetes, and fatty liver disease. Inflammation, oxidative stress, lipid remodeling, and hyperinsulinemia/insulin-like growth factor signaling can promote tumor development and worse outcomes (with reported “obesity paradox” findings likely influenced by bias and measurement limits). Visceral and perivascular/epicardial fat contribute to hypertension, atherosclerosis, and heart failure via lipotoxicity, cytokines, and hemodynamic strain. Brown fat may be protective but is often reduced in obesity. For type 2 diabetes mellitus, free fatty acids and inflammatory signaling disrupt insulin pathways and impair β-cells; For non-alcoholic fatty liver disease/nonalcoholic steatohepatitis, insulin resistance and hepatic lipid overload drive steatosis, injury, fibrosis, and sometimes hepatocellular carcinoma. Treatment centers on diet/activity, bariatric surgery for selected patients, and medications (including GLP-1 receptor agonists), with ongoing need for therapies that improve cardiovascular outcomes.

Reference: Jin X, Qiu T, Li L, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023 Jun;13(6):2403-2424. doi: 10.1016/j.apsb.2023.01.012.

Weight stigma is common in both social and healthcare settings, yet it’s still not consistently addressed within obesity management. This review argues that comprehensive, stigma-reduction interventions—and especially reviews that assess them—have been lacking, and it aims to close that gap. Using a PRISMA-guided approach, the authors synthesize evidence on how interventions targeting weight stigma can improve psychological outcomes and behavioral outcomes.

To identify relevant evidence, the authors searched a variety of databases for studies published from 1975 through January 2024, using a structured MEDLINE-style keyword strategy, plus supplementary Google Scholar and reference-list searching. Studies were screened using a PICOS framework focused on adults experiencing weight stigma, with psychological/behavioral interventions compared against standard care, alternative approaches, or no treatment. Outcomes included reductions in stigma and improvements in quality of life and body image. Across studies, many interventions reduced internalized weight bias and improved related outcomes. Effects were often stronger and more durable when programs were longer, included support/coaching, and addressed related mediators (eg, shame, self-criticism, avoidance) rather than focusing on stigma alone.

Reference: Ramsamy G, Mosbah H, Faure JP, et al. How to reduce the adverse effects of weight stigma on the quality of life: a preferred reported items for systematic reviews and meta-analyses (PRISMA). Front Psychol. 2024 Dec 24;15:1421609. doi: 10.3389/fpsyg.2024.1421609.

Authors of this pilot study evaluated the Primary Care Integrated Weight Management (PCIWM) program, which adapts the collaborative care management model—traditionally used for behavioral health—to obesity care in primary care settings. Implemented through an academic medical center and four rural South Carolina clinics, the program brought together registered dietitians, primary care providers, practice managers, and a weight management consultant to deliver coordinated, largely virtual weight management support. Adults with weight-related concerns, especially those with a body mass index (BMI) above 25 kg/m², received nutrition assessments, goal setting, medical nutrition therapy, and optional monthly follow-up sessions. The study aimed to describe how the model was implemented and identify ways to improve adoption and long-term sustainability.

Early findings suggest the model is feasible and potentially promising, particularly for rural populations with limited access to structured weight management services. Among 61 participants, the average age was 46.8 years, most were women, and the mean baseline BMI was 41.82. Nearly 29% remained actively engaged, averaging 3.4 dietitian visits, and more than half of those with follow-up weight data either maintained or lost weight. Survey responses also showed that many participants were adhering to their health goals, and overall mean BMI fell by 2.7%. The authors conclude that PCIWM offers a novel virtual care approach for obesity management, but broader research, policy support, and program expansion are needed to strengthen long-term impact on weight and cardiometabolic health.

Reference: Hales S, Koob C, Harvey J, et al. Implementing a Virtual, Collaborative Care Weight Management Program in Rural Primary Care: Pilot Results and Insights. Telemed Rep. 2025;6(1):341-351. doi: 10.1177/26924366251385717.

This American Diabetes Association “Standards of Care in Diabetes” section outlines evidence-based obesity management for adults with type 2 diabetes and those at risk, emphasizing person-centered, nonjudgmental care. It recommends measuring height/weight and calculating body mass index (BMI) at least annually (more often when indicated), tracking weight trajectory, and ensuring privacy during weigh-ins. Clinicians should note BMI limitations (including lower cut points in some populations) and consider fat distribution and weight patterns. Modest weight loss (about 3%-7%) improves glycemia and cardiovascular risk factors, while larger sustained losses (>10%) can deliver greater benefits, including possible type 2 diabetes remission and better long-term outcomes.

Lifestyle intervention is the foundation: nutrition, physical activity, and behavioral therapy targeting at least 5% weight loss, with high-intensity support (≥16 sessions in 6 months) and a typical 500 to 750 kcal/day deficit, tailored to preferences and social determinants. Long-term maintenance (≥1 year) with at least monthly contact, frequent self-monitoring, and 200 to 300 minutes/week of activity is recommended. Very low-calorie meal plans may be used short-term with close monitoring; supplements lack evidence. Pharmacotherapy can be added for selected patients (generally BMI ≥27 kg/m²), favoring weight-beneficial diabetes medication and minimizing weight-gain drugs; continue if ≥5% loss at 3 months. Metabolic surgery is recommended for appropriate candidates (typically BMI ≥40, or ≥35 if nonsurgical methods fail; lower thresholds may be considered), done in experienced centers with psychological screening and lifelong nutritional monitoring.

Reference: ElSayed NA, Aleppo G, Aroda VR, et al. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S128-S139. doi: 10.2337/dc23-S008.

This 2025 AACE consensus statement updates the organization’s obesity algorithm by framing obesity as adiposity-based chronic disease: a chronic, heterogeneous, neuroendocrine disease that requires long-term care rather than short-term weight-loss efforts alone. The guidance emphasizes a person-centered, complication-centric model in which clinicians diagnose and stage disease using both an anthropometric component—body mass index (BMI) plus physical confirmation of excess adiposity, waist measures, and sometimes body-composition tools—and a clinical component based on the presence and severity of obesity-related complications and diseases (ORCD). In this framework, stage 1 refers to “preclinical” obesity without established complications but still warrants treatment to prevent progression. Stages 2 and 3 reflect mild-to-moderate or severe ORCD and help determine treatment intensity. The statement also repeatedly stresses shared decision-making, long-term follow-up, and the need to reduce weight bias and stigma as part of high-quality obesity care.

On treatment, the update moves beyond a singular focus on BMI or pounds lost. Instead, it prioritizes improving health outcomes tied to specific complications. Lifestyle and behavioral therapy remain foundational, but pharmacotherapy should be individualized based on complication profile, efficacy, adverse effects, and cost/access. The document notes that second-generation anti-obesity medications such as semaglutide and tirzepatide generally produce greater average weight loss and are especially important when more substantial loss is needed. First-generation options still have an important role as well, particularly in stage 1 or 2 disease and when cost or insurance barriers limit access. It also supports metabolic/bariatric surgery as a highly effective option for appropriate patients, generally including BMI thresholds of at least 40 or at least 35 with complications. It further warns that obesity care should not be reduced to online prescribing without proper evaluation and follow-up.

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Reference: Nadolsky K, Garvey WT, Agarwal M, et al. American Association of Clinical Endocrinology Consensus Statement: Algorithm for the Evaluation and Treatment of Adults with Obesity/Adiposity-Based Chronic Disease—2025 Update. Endocr Pract. 2025;31:1351-1394. doi: 10.1016/j.eprac.2025.07.017. Epub 2025 Sep 16.

Authors of this review outline how pediatric obesity is assessed in practice using body mass index (BMI) percentiles, while noting BMI’s limits as a stand-in for adiposity. They also review key drivers, including appetite regulation via the gut–brain axis, mixed evidence on microbiome contributions, and genetic influences ranging from rare monogenic/syndromic forms to common polygenic risk amplified by calorie-dense, low-activity environments. Early feeding patterns, family food practices, and increasing peer influence and autonomy during adolescence further shape eating behaviors and activity.

Clinically, the review highlights obesity’s downstream impacts across childhood and adolescence—cardiometabolic risk (hypertension, dyslipidemia, prediabetes/type 2 diabetes), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, sleep apnea, orthopedic complications, and effects on growth and puberty—along with the importance of screening for metabolic syndrome risk factors and sleep behaviors. For management, it prioritizes prevention and family-based, multicomponent behavioral treatment as the gold standard, emphasizing that stigmatizing language can reduce engagement and that motivational interviewing can support sustainable change. When lifestyle strategies aren’t enough, multidisciplinary programs may help. Bariatric surgery is reserved for carefully selected adolescents with severe obesity and significant comorbidities, supported by long-term multidisciplinary follow-up and broader environmental/policy efforts.

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Reference: Kansra AR, Lakkunarajah S, Jay MS. Childhood and Adolescent Obesity: A Review. Front Pediatr. 2021 Jan 12;8:581461. doi: 10.3389/fped.2020.581461.

This review frames obesity as a chronic, multifactorial disease with major clinical, social, and economic consequences, arguing that body mass index (BMI)-only definitions are increasingly inadequate. It summarizes how classification is evolving toward more holistic staging (eg, clinical vs pre-clinical obesity) that incorporates adiposity-related complications, metabolic biomarkers, and functional impact, alongside tools like waist circumference and staging systems that consider quality of life and mental health. The authors highlight BMI’s key limitations—poor discrimination of fat vs lean mass, failure to capture visceral fat risk, and reduced accuracy across ethnic groups—driving interest in diagnostics that better reflect metabolic health while remaining feasible in routine care.

Risk is shaped by genetics/epigenetics interacting with an “obesogenic” environment (ultra-processed foods, sedentary behavior, poor sleep), socioeconomic stressors and psychology, endocrine disruptors, microbiome changes, and iatrogenic causes (notably weight-promoting medications). Health impacts span insulin resistance/metabolic syndrome, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, cardiovascular and respiratory disease, chronic kidney disease, osteoarthritis, cancer risk, and neuroendocrine/mental health effects. Treatment is presented as a continuum: lifestyle and behavioral support as foundational, older drugs and bariatric surgery as established options, and newer incretin-based therapies as transformational but limited by tolerability, access, and weight regain after discontinuation. The review reinforces the need for long-term, multidisciplinary care and future research into combination regimens plus emerging approaches, including epigenetic, microbiome, and RNA-based strategies.

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Reference: Ullah MI, Tamanna S. Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies. Medicines (Basel). 2025 Jul 28;12(3):19. doi: 10.3390/medicines12030019

The Harvard Nutrition Obesity Research Center convened a symposium on “Novel Strategies for Medical Management of Obesity,” reflecting the rapid evolution of obesity therapeutics. Experts from the United States and abroad presented across four themes: mechanisms and clinical implications of current strategies, targeting brain pathways to reduce hunger, equity/cost/access, and integrating pharmacotherapy into durable long-term care.

A major focus was the new era of incretin-based therapies (notably GLP-1 receptor agonists and related dual/triple agonists) that can deliver weight loss approaching surgical outcomes and confer benefits beyond weight—cardiovascular event reduction, improved heart failure symptoms, kidney protection in type 2 diabetes, and potential impacts on cravings and reward pathways. The report also highlights emerging pipeline options, treatments for genetic/hypothalamic obesity, and the importance of preventing weight regain given the body’s defended “set point.” Speakers addressed risks and practical considerations (gastrointestinal effects, peri-procedural guidance, lean-mass/bone concerns—especially in older adults), plus the policy reality that access remains. The speakers concluded that long-term success will depend on comprehensive maintenance strategies, muscle-preserving approaches, better biomarkers for response, and equitable access.

Reference: Srivastava G, Campbell SL, Hill CR, et al. Novel strategies for medical management of obesity: mechanisms, clinical implications, and societal impacts-a report from the 25th Annual Harvard Nutrition Obesity Symposium. Am J Clin Nutr. 2025 Sep;122(3):866-885. doi: 10.1016/j.ajcnut.2025.06.015.