Obesity: What We Know and What We Can Do?

Introduction and scope

Obesity is a chronic, relapsing, multifactorial disease marked by excess adiposity that impairs health. It now affects more than one billion people worldwide, including over 650 million adults, with prevalence rising in nearly every region and across all socioeconomic strata. Obesity substantially increases risks of type 2 diabetes, cardiovascular disease, certain cancers, musculoskeletal disorders, sleep apnea, infertility, and mental health conditions, among others, and contributes to reduced life expectancy and quality of life. Its economic burden is profound through direct medical costs and indirect productivity losses. Importantly, individuals with obesity frequently encounter stigma and bias in healthcare, workplaces, and society, which itself harms health and impedes care. Addressing obesity demands both clinical and public health strategies that recognize its biological underpinnings, environmental drivers, and social determinants.[1–5]

Biology and pathophysiology: why body weight is “defended”

Body weight is regulated by a complex neuroendocrine system that evolved to preserve energy stores in environments where food scarcity was common. The hypothalamus integrates peripheral signals of energy status—leptin from adipose tissue; insulin from the pancreas; gut-derived hormones such as ghrelin (orexigenic) and GLP-1, PYY, and CCK (anorexigenic)—with neural inputs from the brainstem and reward circuits to modulate appetite, satiety, and energy expenditure.[6,7] In a state of positive energy balance, expanding adipose mass increases leptin and insulin, which normally reduce food intake and increase energy expenditure. In common obesity, however, central resistance to these signals develops, so higher leptin levels fail to adequately suppress appetite or prevent further weight gain.[6]

The body’s response to weight loss further illustrates its homeostatic defense: energy restriction reduces leptin and insulin and increases ghrelin, intensifying hunger; resting energy expenditure decreases beyond what is expected from reduced body mass (adaptive thermogenesis). These biological adaptations persist for months to years and help explain weight-loss plateaus and regain after dieting.[6,7]

Genetics and development

Genetic factors contribute substantially to interindividual variability in susceptibility to obesity. Rare monogenic forms (for example, congenital leptin deficiency, melanocortin 4 receptor [MC4R] mutations) cause severe early-onset obesity; more commonly, obesity is polygenic, with many loci of small effect contributing to risk. In utero and early-life factors—maternal hyperglycemia, smoking, rapid infant weight gain—can epigenetically program increased risk. The microbiome, sleep, circadian rhythms, endocrine disruptors, medications (e.g., antipsychotics, some antidepressants, insulin, sulfonylureas, corticosteroids), chronic stress, and socioeconomic disadvantage all interact with genetic susceptibility to shape obesity risk across the life course.[3,6]

An obesogenic environment

Today’s food and activity environments promote weight gain: ubiquitous availability and marketing of highly palatable, energy-dense foods; large portion sizes; sugar-sweetened beverages; sedentary occupations; car-centric urban design; and limited opportunities for safe physical activity. These environmental and structural factors make sustained behavioral change challenging without supportive policies and systems.[1,3]

Classification and measurement

• Body mass index (BMI) is weight (kg)/height (m2). In adults, BMI 25.0–29.9 kg/m2 is overweight; ≥30.0 is obesity; ≥35 and ≥40 indicate severe classes. BMI is easy to measure and correlates with adiposity and health risks but does not directly capture fat distribution or account for differences in body composition across sex, age, and ethnicity.[1,2]
• Central adiposity: Waist circumference and waist–hip ratio better reflect visceral adipose tissue, a strong predictor of cardiometabolic risk. WHO expert consensus provides population-specific cut points and emphasizes their use alongside BMI.[8]
• In children and adolescents, BMI-for-age percentiles (WHO and CDC growth references) define overweight and obesity relative to age and sex norms.[1,26]
• Body composition methods (bioimpedance, DXA) and clinical concepts (e.g., sarcopenic obesity) refine risk assessment in selected settings but are not required for routine diagnosis.[2,3]

Health consequences

Obesity increases incidence and worsens outcomes of:

• Cardiometabolic disease: insulin resistance, prediabetes and type 2 diabetes, dyslipidemia, hypertension, coronary artery disease, stroke, heart failure with preserved ejection fraction, and atrial fibrillation.[2,3,9]
• Hepatic and gastrointestinal disease: nonalcoholic fatty liver disease (now termed MASLD), gallstones, GERD, pancreatitis, colorectal cancer risk.[2,3]
• Respiratory disorders: obstructive sleep apnea, obesity hypoventilation syndrome, asthma severity.[2,3]
• Musculoskeletal and dermatologic conditions: osteoarthritis (especially knee), back pain, intertrigo, hidradenitis suppurativa.[2,3,9]
• Reproductive and endocrine disorders: polycystic ovary syndrome, infertility, complications in pregnancy (gestational diabetes, preeclampsia), hypogonadism in men.[2,3]
• Cancers: increased risk of postmenopausal breast, endometrial, colorectal, kidney, pancreatic, liver, and others.[1–3,9]
• Mental health: depression, anxiety, binge-eating disorder; and harms of weight stigma including avoidance of care, disordered eating, and physiologic stress responses.[2,5]

Assessment in clinical practice

Principles

• Treat obesity as a chronic disease with biological, behavioral, environmental, and social determinants.
• Provide respectful, person-centered, stigma-free care; ask permission to discuss weight; focus on health goals important to the person.[2,3,5,11,12]

History and examination

• Weight history: onset and trajectory, highest/lowest adult weight, prior attempts and responses, triggers for gain/loss.
• Lifestyle: dietary patterns and context, physical activity and sedentary time, sleep quantity/quality, stress, substance use, food insecurity.
• Medical conditions/medications that promote weight gain; comorbidities (diabetes, hypertension, dyslipidemia, OSA, osteoarthritis, GERD, liver disease, depression/anxiety, eating disorders).
• Psychosocial factors: mental health, social support, socioeconomic barriers, experiences of stigma; readiness, confidence, and preferences.
• Physical exam: BMI, waist circumference, blood pressure, signs of secondary endocrine causes (rare), osteoarthritis, acanthosis nigricans, edema, respiratory pattern, skin conditions.[2,3,11,12]

Laboratory and investigations

• Suggested baseline screening: fasting lipid panel, fasting glucose or HbA1c, liver aminotransferases; additional tests guided by clinical context (TSH for suspected hypothyroidism; polysomnography for OSA symptoms; pregnancy testing if relevant; assessment for NAFLD with noninvasive scores).[2,3,11,12]

Risk stratification and staging

• Beyond BMI, stratify by health impact. The Edmonton Obesity Staging System (EOSS) classifies stages 0–4 based on metabolic, physical, and psychological comorbidities and functional status, with prognostic value for mortality and guiding intensity of management.[10,11]

What we can do: management strategies

General approach

A comprehensive plan typically combines dietary energy deficit and nutrition quality, physical activity, behavior-change support, and appropriate use of pharmacotherapy or surgery. Obesity care is most effective when individualized, sustained over time, and embedded in a supportive system that addresses barriers and comorbidities. Realistic expectations matter: 5–10% sustained weight loss improves many risk factors and outcomes; greater losses may achieve remission of some conditions.[2,3,11,12]

Behavioral and lifestyle therapies

Nutrition and dietary patterns

• Energy deficit is essential for weight loss but can be achieved with various dietary patterns when matched to a person’s preferences, culture, comorbidities, and ability to sustain. Emphasize minimally processed foods; vegetables, fruits, legumes, and whole grains; adequate protein; healthy fats; reduced added sugars and refined starches; and attention to portion sizes.[12,15]
• Common approaches include Mediterranean-style, DASH, low-carbohydrate, low-fat, and higher-protein diets; structured meal replacements can augment early loss. Comparative trials show broadly similar long-term results when adherence is similar; the best diet is the one an individual can maintain.[2,3,12,15]
• Practical tools: dietary self-monitoring; planning meals; limiting energy-dense snacks and sugar-sweetened beverages; mindful eating; addressing binge or emotional eating when present.[12,15]
• Special contexts: protein adequacy (especially in older adults) to preserve lean mass; micronutrient sufficiency; culturally tailored counseling; management of food insecurity.[2,3]

Physical activity and sedentary behavior

• Physical activity improves cardiometabolic risk, fitness, mood, and weight maintenance. While exercise alone yields modest weight loss for most, it is critical for long-term maintenance and overall health.[12,14]
• WHO recommendations for adults: at least 150–300 minutes/week of moderate-intensity aerobic activity (or 75–150 minutes vigorous), plus muscle-strengthening activities on 2 or more days; reduce sedentary time and break up prolonged sitting.[14]
• For weight-loss maintenance, higher volumes (200–300 minutes/week) are often needed; incorporate resistance training to preserve lean mass during weight loss.12,14
• Tailor to comorbidities (e.g., low-impact options for osteoarthritis) and preferences; use activity tracking and graded goals.[12,14]

Sleep, stress, and behavior strategies

• Inadequate sleep and circadian disruption increase hunger and impair glucose regulation; aim for 7 or more hours of quality sleep in adults and address sleep apnea when suspected.[16]
• Behavioral weight management programs with frequent contact (at least 12 sessions over 6 months) employing self-monitoring, goal setting, problem solving, stimulus control, and relapse prevention produce clinically meaningful weight loss. Motivational interviewing and cognitive-behavioral strategies enhance adherence.[11,12,13]
• Digital tools (apps, connected scales), group sessions, meal planning supports, and family or peer involvement can improve reach and maintenance.[11–13]

Pharmacotherapy

Indications and principles

• Consider anti-obesity medications for adults with BMI ≥30 kg/m2, or ≥27 kg/m2 with weight-related comorbidities (e.g., hypertension, type 2 diabetes, dyslipidemia, OSA), when lifestyle measures alone are insufficient. Use as adjuncts to lifestyle, not replacements, within a chronic care model.[11,12,17,18]
• Selection depends on efficacy, safety, comorbidities, contraindications, patient preference, cost/access, and pregnancy plans. Monitor response and tolerability; continue if weight loss ≥5% at 3 months on the therapeutic dose (or clinically meaningful improvements in comorbidities); discontinue if ineffective or not tolerated.[17,18]

Medication classes and evidence

Gastrointestinal fat absorption inhibitor:

• Orlistat reduces dietary fat absorption by inhibiting pancreatic lipase, leading to modest additional weight loss versus lifestyle alone and improvements in LDL cholesterol. Common adverse effects are gastrointestinal (steatorrhea, urgency), mitigated by low-fat intake; supplement fat-soluble vitamins.[17,18]

Central appetite/weight regulation agents (combinations and incretin-based therapies):

• Naltrexone-bupropion combination acts on reward pathways and hypothalamus to reduce appetite and cravings; typical additional weight loss is moderate, with potential increases in blood pressure and heart rate; avoid in uncontrolled hypertension, seizure disorder, or chronic opioid therapy.[17,18]
• Phentermine-topiramate extended-release offers among the greater average losses among older agents; monitor for teratogenicity (topiramate), paresthesias, insomnia, heart rate elevations; use pregnancy prevention and periodic reassessment.[17]

GLP-1 receptor agonists:

• Liraglutide 3.0 mg daily and semaglutide 2.4 mg weekly reduce appetite, slow gastric emptying, and enhance satiety; semaglutide 2.4 mg produces substantial mean weight loss and cardiometabolic benefits in randomized trials when combined with behavioral support. Gastrointestinal symptoms are common; rare risks include gallbladder disease; avoid with personal/family history of medullary thyroid carcinoma or MEN2.[17–19]
• Tirzepatide, a dual GIP/GLP-1 receptor agonist approved for chronic weight management, has produced large mean weight losses across BMI ranges in adults with obesity, with safety profile similar to GLP-1 RAs (gastrointestinal adverse events most common).[19,20]
• Other agents and emerging therapies are evolving; practice guidelines and labeling should guide up-to-date use, dosing, and monitoring.[17,18]

Endoscopic devices and procedures

• Endoscopic bariatric therapies (e.g., intragastric balloons, endoscopic sleeve gastroplasty) can induce clinically meaningful weight loss in selected patients and may bridge to surgery or serve those who cannot access or do not desire surgery. Candidates, efficacy, and risks vary by device; availability differs by country. Multidisciplinary follow-up and behavioral care remain essential.[2,3]

Metabolic and bariatric surgery

Indications and procedures

• Metabolic/bariatric surgery is the most effective and durable treatment for severe obesity and can produce remission or marked improvement of many comorbidities (notably type 2 diabetes). Contemporary guidelines recommend surgery for individuals with BMI ≥40 kg/m2, or ≥35 kg/m2 with at least one serious obesity-related condition; many societies now support considering surgery for BMI 30–34.9 kg/m2 with difficult-to-control type 2 diabetes or metabolic disease after nonsurgical therapies.[11,21,24]
• Common procedures include sleeve gastrectomy and Roux-en-Y gastric bypass; biliopancreatic diversion with duodenal switch is less common but yields the greatest weight loss with higher nutritional risk. Perioperative mortality in experienced centers is low (often <0.3%), but lifelong follow-up is required.[2,3,21,24]

Outcomes and risks

• Sustained weight loss often exceeds 20–30% of initial body weight, with improvements in hypertension, dyslipidemia, OSA, NAFLD, and quality of life; large cohort data show reductions in all-cause and cardiovascular mortality compared with nonsurgical care.[22]
• Randomized trials demonstrate superior glycemic control and higher rates of diabetes remission compared with intensive medical therapy, particularly with gastric bypass and sleeve gastrectomy, alongside reductions in medication burden.[23]
• Risks include surgical complications (leaks, bleeding, strictures), micronutrient deficiencies (iron, B12, folate, vitamin D, calcium, others), dumping syndrome, hypoglycemia, kidney stones, alcohol use disorder, and weight regain in a minority; structured, lifelong nutritional monitoring and supplementation are essential.[2,3,21,24]

Special populations and considerations

• Children and adolescents: Early identification using age- and sex-specific BMI percentiles; intensive, family-based, multicomponent behavioral interventions (high contact hours) improve weight and health outcomes. Pharmacotherapy and metabolic surgery can be considered in selected adolescents with severe obesity within specialist programs.[1,25,26]
• Pregnancy: Preconception weight optimization reduces pregnancy risks; during pregnancy, weight-loss medications are contraindicated; focus on healthy gestational weight gain targets, nutrition quality, and activity; postpartum support for weight and lactation.[2,3]
• Older adults: Balance weight-loss benefits against risks of sarcopenia and bone loss; prioritize resistance training, protein adequacy, and cautious energy restriction.[2,3]
• Cultural and ethnic considerations: Some populations experience higher cardiometabolic risk at lower BMI; waist measures and risk-factor burden can inform thresholds and urgency of intervention.[1,8]
• Mental health and eating disorders: Screen for binge-eating disorder, depression, anxiety; integrate psychotherapy when indicated; avoid medications that exacerbate weight gain when alternatives exist.[2,3,5,11]

Implementing care: practical steps for clinicians

• Partner on goals that matter to the person (e.g., mobility, glycemic control, sleep, fertility), not only the scale. Agree on realistic targets (initial 5–10% loss), timelines, and follow-up.[2,11,12]
• Offer or refer to a structured behavioral weight-management program with frequent contact, self-monitoring tools, and skill-building.[11–13]
• Review medications; when possible, substitute weight-promoting agents (e.g., some antipsychotics, antidepressants, beta-blockers, insulin secretagogues) with weight-neutral or weight-reducing alternatives (e.g., metformin, SGLT2 inhibitors, GLP-1 RAs for diabetes; mindful of indications/risks).[2,3,11]
• Discuss pharmacotherapy when criteria are met and meaningful health benefits are likely; set expectations about efficacy, side effects, costs, and the need for ongoing use to maintain benefits.[17,18]
• Consider surgical referral for eligible patients after shared decision-making that includes risks, benefits, and required follow-up.[21,24]
• Plan for maintenance: schedule ongoing support, reinforce physical activity, adequate protein, problem-solving, and rapid response to weight regain signals; normalize relapse as part of chronic disease management.[12,30]

Public health and policy: shifting environments and systems

Individual counseling alone cannot reverse population trends without supportive environments. Effective strategies include:

• Promoting healthy food environments: front-of-pack nutrition labels; reformulation targets; limits on trans fats; marketing restrictions for unhealthy foods to children; procurement standards for schools, hospitals, and public programs.[1,27,28]
• Fiscal policies: taxes on sugar-sweetened beverages and certain unhealthy foods, and subsidies or incentives for healthier options, which can reduce purchases of taxed items and encourage reformulation.[28]
• Built environment and active transport: urban design that supports walking, cycling, and public transit; access to safe parks and recreational facilities.14
• Early-life interventions: breastfeeding support; healthy school meals; school-based physical activity and nutrition curricula; restrictions on in-school sales of sugar-sweetened beverages and energy-dense snacks.[1,27]
• Worksite and community programs: multicomponent interventions that combine nutrition, physical activity, and behavior-change supports have demonstrated benefits.[29]
• Addressing social determinants: poverty, food insecurity, housing and neighborhood safety, education, and access to healthcare shape obesity risk and outcomes; policies that improve these determinants are foundational.[1,27]
• Reducing stigma: public messaging that avoids blame, training for healthcare and educators to reduce weight bias, and anti-discrimination protections.[5,27]

Future directions

Advances in pharmacotherapy, including next-generation incretin-based and multi-agonist agents, are expanding options and may transform outcomes for many. Precision approaches that integrate genetics, phenotypes (e.g., hyperphagia, emotional eating), metabolic profiling, and digital phenotyping could guide therapy selection. Scalable digital therapeutics, remote monitoring, and AI-supported coaching may extend reach and sustain engagement. Continued innovation in endoscopic therapies may fill gaps between medications and surgery. These clinical advances must be paired with stronger prevention policies and systems-level changes to reduce incidence, narrow inequities, and sustain health gains.[2,3,12]

Conclusion

Obesity is a common, serious, and complex chronic disease with biological roots and environmental drivers. Its complications are broad but often reversible with sustained, evidence-based care. We know that modest sustained weight loss confers meaningful health benefits, that comprehensive behavioral programs work, that pharmacotherapy and surgery can be safe and highly effective for appropriate candidates, and that supportive environments and policies are indispensable. What we can do—clinically and societally—is clear: deliver respectful, person-centered chronic care; deploy effective therapies earlier; build healthier food and activity environments; and address the social determinants and stigma that perpetuate the problem. With coordinated action, we can improve the lives of people living with obesity and reduce its burden on communities and health systems.

References

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