Obesity

(Redirected from Obese)
Jump to navigation Jump to search

Template:DiseaseDisorder infobox For patient information click here

Obesity Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Obesity from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Lifestyle Intervention and Counseling (Comprehensive Lifestyle Intervention)

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

USPSTF Recommendations and Guidelines on Management of Obesity

2017 Guidelines for Screening of Obesity in Children and Adolescents

2012 Guidelines for Screening of Obesity in Adults

AHA/ACC/TOS Guidelines on Management of Overweight and Obesity

2013 AHA/ACC/TOS Guidelines on Management of Overweight and Obesity

Obesity On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Obesity

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Obesity

CDC on Obesity

Obesity in the news

Blogs on Obesity

Directions to Hospitals Treating Obesity

Risk calculators and risk factors for Obesity

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omar Elshafei, MD[2] Cafer Zorkun, M.D., Ph.D. [3] Raviteja Guddeti, M.B.B.S. [4] Parth Vikram Singh, MBBS[5] Synonyms and keywords: Adiposity; excess adiposity; adiposity-based chronic disease; ABCD; clinical obesity; preclinical obesity; corpulence

Overview

Obesity is a chronic, relapsing, progressive disease characterised by excess or dysfunctional adipose tissue that impairs health. It is not a behavioural failing and it is not defined by appearance. Excess adiposity acts through mechanical loading, ectopic lipid deposition, chronic low-grade inflammation and altered adipokine and incretin signalling to increase the risk of type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, heart failure with preserved ejection fraction, obstructive sleep apnea, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, osteoarthritis and at least a dozen cancers.

Historically obesity was defined by body mass index alone. Contemporary frameworks retain BMI as a screening tool but no longer accept it as a diagnosis on its own, because BMI cannot distinguish fat mass from lean mass, cannot localise adiposity, and performs differently across ancestries. Current practice therefore combines BMI with a confirmatory measure of adiposity such as waist circumference or waist-to-height ratio, followed by clinical staging that separates people who already have organ dysfunction attributable to adiposity from those who carry excess adiposity with preserved organ function. This distinction, expressed as clinical versus preclinical obesity, determines both the urgency and the intensity of treatment.

Management is complication-centric rather than weight-centric. Structured lifestyle intervention remains the foundation and is sufficient for some patients, but the therapeutic landscape has changed fundamentally with the incretin-based agents. Semaglutide and tirzepatide now produce mean weight reductions in the range historically achievable only with surgery, and, more importantly, have demonstrated benefit on hard outcomes including major adverse cardiovascular events, heart failure symptoms, sleep apnoea severity, kidney endpoints and liver histology. Oral small-molecule and combination amylin-based agents have entered practice. Metabolic and bariatric surgery remains the most durable intervention and is associated with substantially longer life expectancy, particularly in patients with type 2 diabetes mellitus.

The single most important principle for the clinician is chronicity. Weight regain after discontinuation of pharmacotherapy is the rule rather than the exception, and randomised evidence now supports continued therapy, with dose reduction as an intermediate option, rather than treatment cessation once a weight target is reached. Weight bias and stigma are themselves barriers to care and should be addressed explicitly in the clinical encounter.

Historical Perspective

  • Depictions of obesity appear in Palaeolithic figurines, and physicians from Hippocrates onward recorded associations between corpulence, sudden death and infertility.
  • For most of recorded history, adiposity signalled prosperity in food-scarce societies. The epidemiological reversal, in which obesity became concentrated in lower socioeconomic groups in high-income countries, is a twentieth century phenomenon.
  • The body mass index derives from the Quetelet index described in the nineteenth century as a population statistic, not as a clinical diagnostic instrument. Its later adoption as a diagnostic threshold is the source of much of the current controversy about its use.
  • Life insurance actuarial tables in the early twentieth century provided the first large-scale quantitative link between excess weight and mortality.
  • The Swedish Obese Subjects study, initiated in 1987, was the first large prospective controlled study to demonstrate that surgically induced weight loss reduces mortality.[1]
  • The Diabetes Prevention Program established in 2002 that modest weight loss achieved by intensive lifestyle intervention prevents progression to type 2 diabetes mellitus.[2]
  • Recognition of obesity as a disease by major medical bodies, and the arrival of incretin-based pharmacotherapy in the 2020s, shifted obesity care from a behavioural counselling model to a chronic disease management model.
  • In 2025 an international commission proposed formal diagnostic criteria separating clinical obesity, in which excess adiposity has caused organ or tissue dysfunction, from preclinical obesity, in which it has not.[3]

Classification

Anthropometric Classification

Body mass index is calculated as weight in kilograms divided by the square of height in metres. It remains the recommended initial screening measure but should be confirmed by a measure of central adiposity before a diagnosis is assigned.[4]

Category BMI (kg/m2) Clinical comment
Underweight Less than 18.5 Requires separate evaluation for malnutrition and secondary causes
Normal weight 18.5 to 24.9 Reference range in which all-cause mortality is lowest
Overweight 25.0 to 29.9 Pharmacotherapy considered when a weight-related complication is present
Obesity class I 30.0 to 34.9 Threshold for diagnosis of obesity in most populations
Obesity class II 35.0 to 39.9 Metabolic and bariatric surgery indicated irrespective of comorbidity
Obesity class III (severe obesity) 40.0 or greater Highest risk of mechanical, respiratory and cardiovascular complications

Ancestry matters. Because visceral adiposity and cardiometabolic risk occur at lower BMI values in several populations, particularly individuals of Asian ancestry, current standards recommend race- and ethnicity-specific BMI thresholds supplemented by waist-based measures rather than a single universal cutoff.[4] Applying uncorrected European-derived thresholds systematically underdiagnoses obesity in these groups.

Measure of central adiposity Threshold suggesting increased risk
Waist circumference, men 102 cm (40 inches) or greater
Waist circumference, women 88 cm (35 inches) or greater
Waist-to-height ratio, both sexes 0.5 or greater

Waist circumference thresholds are those of the joint cardiovascular society guideline and should be interpreted with ancestry-specific adjustment.[5]

Clinical Versus Preclinical Obesity

Category Definition Implication
Preclinical obesity Confirmed excess adiposity with preserved function of organs and tissues A state of increased risk. Management is risk reduction and prevention of progression
Clinical obesity Confirmed excess adiposity with objective signs or symptoms of reduced organ or tissue function attributable to that adiposity A chronic illness in its own right. Management is treatment of established disease

This framework was proposed to prevent both overdiagnosis in people with high BMI and preserved health, and underdiagnosis in people with organ dysfunction from adiposity at BMI values below conventional thresholds.[3]

Functional and Complication-Based Staging

  • The Edmonton Obesity Staging System grades patients from stage 0 (no apparent risk factors, physical symptoms or functional limitation) through stage 4 (severe, potentially end-stage disability from obesity-related comorbidity), and predicts mortality more accurately than BMI alone.[6]
  • The European framework stages obesity by aetiology, degree of adiposity and associated complications, and formally incorporates psychological and functional domains.[7]
  • Adiposity-based chronic disease (ABCD) is a complication-centric nomenclature that classifies patients by the presence and severity of adiposity-related complications rather than by BMI, and directs the intensity of therapy accordingly.[8]
  • Sarcopenic obesity, the coexistence of excess adiposity with low skeletal muscle mass and function, is a distinct entity diagnosed by screening, then assessment of muscle function, then body composition, and is staged I or II according to the presence of complications.[9]

Pathophysiology

Energy Homeostasis and Central Regulation

  • Body weight is defended by a hypothalamic control system rather than set by conscious choice. Peripheral signals of energy status, including leptin from adipocytes, insulin from the pancreas, and gut-derived peptides such as glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, amylin and ghrelin, converge on the arcuate nucleus and the melanocortin pathway.[10]
  • Most obesity is associated with leptin resistance rather than leptin deficiency, which is why exogenous leptin is ineffective except in the rare monogenic deficiency states.[10]
  • The pharmacological efficacy of incretin receptor agonists derives from engagement of these same central circuits, which is the mechanistic reason they achieve weight loss that behavioural intervention alone cannot.

Metabolic Adaptation and Weight Regain

  • After weight loss, circulating levels of appetite-regulating hormones shift in a direction that favours weight regain, and these changes persist for at least one year after the intervention ends.[11]
  • Resting metabolic rate falls disproportionately to the loss of lean mass, and this metabolic adaptation can persist for years after substantial weight loss.[12]
  • These two observations together explain why obesity behaves as a relapsing disease and provide the physiological rationale for indefinite rather than time-limited therapy.

Genetic Architecture

  • Common obesity is highly polygenic. Genome-wide association studies have identified numerous loci influencing BMI, with strong enrichment for genes expressed in the central nervous system rather than in adipose tissue, reinforcing the neurobehavioural basis of energy balance.[13]
  • Monogenic obesity results from disruption of the leptin-melanocortin pathway, including biallelic variants in LEP, LEPR, POMC and PCSK1, and heterozygous MC4R variants, the commonest monogenic cause.[14]
  • Identification of these variants is clinically actionable, because melanocortin-4 receptor agonism produces substantial weight reduction in affected individuals.[15]

Adipose Tissue Dysfunction and Systemic Inflammation

  • Adipose tissue functions as an endocrine organ. With expansion it becomes hypoxic and infiltrated by macrophages, producing a low-grade inflammatory state with elevated interleukin-6 and C-reactive protein and reduced adiponectin.
  • Once subcutaneous storage capacity is exceeded, lipid is deposited ectopically in liver, skeletal muscle, pancreas, epicardium and kidney, producing insulin resistance, metabolic dysfunction-associated steatotic liver disease and myocardial remodelling.
  • These pathways are pharmacologically reversible. In a randomised biomarker analysis, tirzepatide reduced high-sensitivity C-reactive protein by 54.6%, interleukin-6 by 30.2%, leptin by 61.4% and plasminogen activator inhibitor-1 antigen by 44.3%, and increased adiponectin by 47.7% at the 15 mg dose over 72 weeks.[16]

Causes

Common Causes

  • Chronic positive energy balance operating on a susceptible polygenic background
  • Obesogenic food environment, in particular the availability of energy-dense ultra-processed foods. In an inpatient randomised crossover trial with diets matched for presented macronutrients, sugar, sodium and fibre, an ultra-processed diet led to greater ad libitum energy intake and weight gain than an unprocessed diet[17]
  • Sedentary occupational and transport patterns
  • Short or disrupted sleep and circadian misalignment including shift work
  • Psychosocial stress, socioeconomic deprivation and food insecurity

Iatrogenic and Drug-Induced Causes

Medication review is a mandatory part of the obesity assessment. A meta-analysis of 257 randomised trials covering 54 drugs and 84,696 patients quantified the effect of commonly prescribed agents on body weight.[18]

Class Associated weight gain Associated weight loss
Antipsychotics Olanzapine 2.4 kg, quetiapine 1.1 kg, risperidone 0.8 kg Not applicable
Antidepressants Amitriptyline 1.8 kg, mirtazapine 1.5 kg Bupropion 1.3 kg, fluoxetine 1.3 kg
Antiepileptics Gabapentin 2.2 kg Zonisamide 7.7 kg, topiramate 3.8 kg
Sulfonylureas Glyburide 2.6 kg, glipizide 2.2 kg, glimepiride 2.1 kg, gliclazide 1.8 kg, tolbutamide 2.8 kg Not applicable
Other glucose-lowering agents Pioglitazone 2.6 kg, sitagliptin 0.55 kg, nateglinide 0.3 kg Metformin 1.1 kg, liraglutide 1.7 kg, exenatide 1.2 kg, pramlintide 2.3 kg, acarbose 0.4 kg, miglitol 0.7 kg

Where a weight-inducing medication cannot be substituted, obesity pharmacotherapy remains effective. In a post hoc analysis of three randomised trials, approximately one fifth of participants used at least one weight-inducing medication concurrently and achieved weight reduction comparable to the primary trial results.[19]

Endocrine, Hypothalamic and Genetic Causes

Differentiating Obesity from other Diseases

Primary obesity is a diagnosis reached after excess adiposity is confirmed and secondary causes have been considered. Secondary causes are uncommon but are disproportionately important because several are specifically treatable. Features suggesting a secondary cause include very early onset, rapid or discordant weight gain, hyperphagia out of proportion to context, disproportionate central fat distribution, developmental delay, hypogonadism, or dysmorphic features.[4][8]

Condition Distinguishing clinical features Suggested initial evaluation
Primary (polygenic) obesity Gradual weight gain from adolescence or adulthood, family history, absence of dysmorphism or endocrine stigmata, proportionate fat distribution BMI, waist circumference, complication screen
Hypothyroidism Cold intolerance, fatigue, constipation, bradycardia, delayed relaxation of reflexes, coarse skin, modest weight gain largely from fluid retention Thyroid stimulating hormone, free T4
Cushing's syndrome Central obesity with thin extremities, proximal myopathy, wide violaceous striae, easy bruising, facial plethora, hypertension, hyperglycaemia, osteoporosis Late-night salivary cortisol, low-dose dexamethasone suppression test or 24-hour urinary free cortisol
Polycystic ovary syndrome Oligomenorrhoea, hirsutism, acne, acanthosis nigricans, subfertility Total and free testosterone, luteinising hormone, follicle stimulating hormone, pelvic ultrasound
Hypothalamic obesity Rapid intractable weight gain after cranial insult, hyperphagia, visual field defect, headache, multiple pituitary hormone deficiencies, disrupted sleep and thermoregulation Pituitary axis testing, magnetic resonance imaging of the brain, formal visual fields
Monogenic obesity (MC4R, LEP, LEPR, POMC, PCSK1) Severe obesity with onset in early childhood, extreme hyperphagia, hyperinsulinaemia, red hair and adrenal insufficiency in POMC deficiency Targeted genetic panel, specialist referral for melanocortin-directed therapy
Prader-Willi syndrome Neonatal hypotonia and poor feeding followed by hyperphagia in childhood, short stature, hypogonadism, characteristic facies, learning difficulty Methylation analysis of chromosome 15q11-q13
Bardet-Biedl syndrome Rod-cone dystrophy, postaxial polydactyly, renal anomalies, hypogonadism, learning difficulty Ophthalmological assessment, renal imaging, genetic panel
Drug-induced weight gain Temporal relationship to initiation of an implicated agent, weight gain plateauing after dose stabilisation Structured medication review[18]
Lipoedema Symmetrical, tender, disproportionate fat deposition of the limbs sparing the feet and hands, poor response to caloric restriction, easy bruising Clinical diagnosis, exclude lymphedema and venous disease
Generalised oedema, ascites or fluid overload Rapid weight gain over days, pitting oedema, dyspnoea, jugular venous distension, hepatomegaly Echocardiography, serum albumin, renal and hepatic panel, B-type natriuretic peptide
Sarcopenic obesity Excess adiposity with reduced grip strength, slow gait speed and functional decline, often in older adults and often at unremarkable BMI Muscle function testing followed by body composition assessment[9]
Muscular habitus with elevated BMI High BMI with normal waist circumference and preserved metabolic profile, high lean mass Waist circumference, body composition assessment
Binge eating disorder Recurrent episodes of eating with a subjective sense of loss of control, marked distress, absence of compensatory behaviours Clinical interview, referral for psychological assessment

Epidemiology and Demographics

Global

  • A pooled analysis of 3663 population-based studies documented rising obesity prevalence in most countries between 1990 and 2022, with the global burden shifting from a predominance of underweight to a predominance of obesity in most regions.[20]
  • Global burden analyses estimate that more than two billion adults were living with overweight or obesity in 2021, with continued increases forecast through 2050 in the absence of major policy change.[21]
  • Child and adolescent overweight and obesity are projected to rise in parallel, with important implications for the future adult disease burden.[22]

United States

  • During August 2021 to August 2023 the prevalence of obesity among adults aged 20 and over was 40.3%, with a prevalence of 39.2% in men and 41.3% in women and no significant difference between sexes.[23]
  • The prevalence of severe obesity was 9.4%, and was higher in women than in men in each age group.[23]
  • Over the preceding decade the age-adjusted prevalence of obesity did not change significantly, whereas the age-adjusted prevalence of severe obesity increased from 7.7% to 9.7%.[23]
  • Age-adjusted estimates for August 2021 to August 2023 were 40.3% for obesity, 9.7% for severe obesity and 31.7% for overweight, giving a combined overweight and obesity prevalence of 72.4%.[24]
  • Among children and adolescents aged 2 to 19 years, obesity prevalence was 21.1% and severe obesity 7%.[24]
  • Modelling studies had projected that severe obesity would become the most common BMI category in several population subgroups, a projection consistent with the observed rise in severe obesity despite the plateau in overall obesity prevalence.[25]

Note for editors: the figure of 42.4%, derived from the 2017 to 2018 survey cycle, is frequently quoted but has been superseded by the estimates above.

Risk Factors

  • Family history of obesity and polygenic susceptibility[13]
  • Early-onset obesity in childhood or adolescence
  • Female sex for severe obesity specifically[23]
  • Lower educational attainment and socioeconomic deprivation[23]
  • Ultra-processed dietary pattern[17]
  • Physical inactivity and prolonged sedentary time
  • Short sleep duration, obstructive sleep apnea and shift work
  • Weight-inducing medications[18]
  • Pregnancy with excessive gestational weight gain and postpartum weight retention
  • Menopause and age-related decline in lean mass
  • Smoking cessation
  • Psychiatric illness, chronic stress and adverse childhood experiences
  • Weight stigma, which is independently associated with disordered eating, avoidance of health care and worse metabolic outcomes[26]

Screening

  • Screen for excess adiposity at least annually in adults using BMI, and monitor for consistent increases in weight over time so that early intervention can prevent progression.[4]
  • Confirm an abnormal BMI with a measure of central adiposity before assigning a diagnosis, using ancestry-appropriate thresholds.[4]
  • Perform a comprehensive clinical evaluation including risk stratification and staging in all adults diagnosed with overweight or obesity.[4]
  • Offer or refer adults with BMI 30 kg/m2 or greater to intensive, multicomponent behavioural interventions. This is a grade B recommendation of the United States Preventive Services Task Force.[27]
  • Measure weight and height with privacy and with equipment appropriate to body size, and seek permission before discussing weight. Anthropometric measurement is a recognised source of stigmatisation.[26]

Screening and Diagnostic Algorithm

 
 
 
 
Adult presenting for care: measure height, weight and BMI at least annually
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI at or above ancestry-adjusted overweight threshold?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No: reassess at next visit and monitor weight trajectory
 
 
 
Yes: measure waist circumference or waist-to-height ratio to confirm excess adiposity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excess adiposity confirmed: take history, examine, and screen for secondary causes and complications
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Organ or tissue dysfunction attributable to adiposity absent: preclinical obesity
 
 
 
Organ or tissue dysfunction attributable to adiposity present: clinical obesity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Risk reduction, prevention of progression, treat coexisting risk factors
 
 
 
Treat as established chronic disease, stage severity, set complication-specific goals

Natural History, Complications and Prognosis

Natural History

  • Untreated obesity is typically progressive, with weight gain continuing through middle age before plateauing or falling in late life.
  • Weight loss achieved by any modality provokes counter-regulatory hormonal and metabolic adaptations that promote regain, so that the untreated natural history after successful weight loss is one of relapse.[11][12]
  • Complication burden accumulates with duration as well as with degree of adiposity, which is why early-onset obesity carries disproportionate lifetime risk.

Complications

System Complications
Cardiovascular Hypertension, dyslipidemia, coronary artery disease, myocardial infarction, atrial fibrillation, heart failure with preserved ejection fraction, stroke, venous thromboembolism[28]
Metabolic Type 2 diabetes mellitus, insulin resistance, metabolic syndrome, gout
Hepatobiliary Metabolic dysfunction-associated steatotic liver disease, steatohepatitis, cirrhosis, cholelithiasis
Respiratory Obstructive sleep apnea, obesity hypoventilation syndrome (Pickwickian syndrome), asthma
Renal Chronic kidney disease, albuminuria, obesity-related glomerulopathy, nephrolithiasis
Musculoskeletal Osteoarthritis of the knee and hip, chronic low back pain, impaired mobility
Reproductive Polycystic ovary syndrome, subfertility, adverse pregnancy outcomes, hypogonadism in men
Oncological Cancers of the oesophagus, gastric cardia, colon and rectum, liver, gallbladder, pancreas, breast in postmenopausal women, corpus uteri, ovary, kidney, thyroid, and multiple myeloma and meningioma[29]
Gastrointestinal Gastroesophageal reflux disease, hiatal hernia
Psychosocial Depression, anxiety, impaired quality of life, internalised weight bias, discrimination in health care and employment[26]

Prognosis

  • All-cause mortality is lowest at a BMI of approximately 20.0 to 25.0 kg/m2 and rises progressively above that range, in an individual-participant analysis of 239 prospective studies.[30]
  • In a collaborative analysis of 57 prospective studies involving 900,000 adults, median survival was reduced by two to four years at BMI 30 to 35 kg/m2 and by eight to ten years at BMI 40 to 45 kg/m2 compared with the reference range.[31]
  • Prognosis is determined more accurately by functional and complication-based staging than by BMI alone.[6]
  • Prognosis is modifiable. Sustained weight reduction of 5% or more improves several cardiometabolic parameters, and reduction of 10% or more is required to modify many obesity-related complications.[32]

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

History and Symptoms

  • Weight trajectory including age of onset, maximum and minimum adult weight, and periods of rapid change
  • Structured medication review for weight-inducing agents[18]
  • Dietary pattern, meal timing, eating behaviour and symptoms suggesting binge eating
  • Physical activity, occupational activity and functional limitation
  • Sleep duration, snoring, witnessed apnoea and daytime somnolence
  • Symptoms of secondary causes including cold intolerance, proximal weakness, easy bruising, menstrual irregularity, visual disturbance and headache
  • Reproductive history, gestational weight gain and gestational diabetes
  • Previous weight management interventions, response and reasons for discontinuation
  • Psychosocial history including mood, stress, food security and experience of weight stigma

Physical Examination

  • Height, weight, BMI and waist circumference measured with appropriate technique and privacy
  • Blood pressure measured with a correctly sized cuff, since an undersized cuff overestimates pressure
  • Acanthosis nigricans and skin tags suggesting insulin resistance
  • Features of Cushing's syndrome such as violaceous striae, facial plethora, dorsocervical fat pad and proximal myopathy
  • Features of hypothyroidism including bradycardia and delayed relaxation of reflexes
  • Hirsutism, acne and androgenic alopecia suggesting polycystic ovary syndrome
  • Dysmorphic features, polydactyly, retinal changes, hypogonadism or developmental delay suggesting syndromic obesity
  • Assessment of mobility, gait speed and grip strength where sarcopenic obesity is suspected[9]
  • Signs of complications including elevated jugular venous pressure, hepatomegaly, peripheral oedema and joint findings

Laboratory Findings

  • Fasting plasma glucose and glycated hemoglobin
  • Fasting lipid profile
  • Liver function tests with non-invasive fibrosis scoring where indicated
  • Thyroid stimulating hormone
  • Renal function with urine albumin-to-creatinine ratio
  • Uric acid where clinically indicated
  • Targeted testing for Cushing's syndrome, polycystic ovary syndrome or hypopituitarism only when clinical features suggest them
  • Genetic testing for monogenic or syndromic obesity in early-onset severe obesity with hyperphagia or syndromic features[14]
  • Preoperative and postoperative micronutrient panel in patients undergoing metabolic and bariatric surgery

Electrocardiogram

Imaging and Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Initial Management

  • Frame treatment around health outcomes and complications rather than weight alone, and set goals collaboratively.[8]
  • Aim for sustained reduction of 5% or more of baseline body weight for some clinically meaningful benefit, and 10% or more to modify many obesity-related complications.[32]
  • Deliver intensive, multicomponent behavioural intervention comprising dietary change, physical activity and behavioural therapy, either directly or by referral.[27]
  • Intensive lifestyle intervention reduced the incidence of type 2 diabetes mellitus by comparison with placebo and with metformin in adults at high risk.[2]
  • In established type 2 diabetes mellitus, intensive lifestyle intervention produced durable weight loss and improved fitness but did not reduce cardiovascular events over a median of 9.6 years, which is an important expectation-setting point when counselling patients.[33]
  • Primary care-led total diet replacement achieved remission of type 2 diabetes mellitus in a substantial proportion of participants, with remission strongly related to the magnitude of weight loss.[34]
  • Macronutrient composition matters less than adherence. A healthy low-fat and a healthy low-carbohydrate diet produced no significant difference in 12-month weight change, and neither genotype pattern nor insulin secretion predicted which diet suited whom.[35]
  • A Mediterranean dietary pattern supplemented with extra-virgin olive oil or nuts reduced major cardiovascular events in people at high cardiovascular risk, supporting diet quality as a target independent of weight.[36]
  • Address weight bias explicitly, use person-first non-judgemental language, and ensure the clinical environment is equipped appropriately.[26]

Medical Therapy

Indications

  • Pharmacotherapy is indicated as an adjunct to lifestyle intervention in adults with BMI 30 kg/m2 or greater, or 27 kg/m2 or greater with a weight-related complication.[37]
  • Prescribe obesity medications only alongside behavioural and lifestyle intervention, after a comprehensive pre-treatment evaluation, and using a person-centred shared decision-making approach.[32]

Choice of Agent

Guidance differs in strength but not in direction, and both positions should be presented to patients.

  • A joint society guidance statement made strong recommendations for bupropion-naltrexone, semaglutide, tirzepatide and setmelanotide on moderate-certainty evidence, and conditional recommendations for the remaining approved agents and for specific complications including obstructive sleep apnea, heart failure with preserved ejection fraction, steatotic liver disease, osteoarthritis, major adverse cardiovascular events and type 2 diabetes mellitus.[38]
  • A living clinical guideline issued conditional recommendations with a line-of-therapy structure: semaglutide and tirzepatide first line on moderate-certainty evidence, phentermine-topiramate second line, liraglutide third line and naltrexone-bupropion fourth line, each on low-certainty evidence. For BMI 27 to 30 kg/m2 with a listed comorbidity, only semaglutide, tirzepatide and liraglutide were recommended.[39]
  • A systematic review and network meta-analysis provides comparative estimates across agents where head-to-head trials are unavailable.[40]
Agent Route Efficacy in the pivotal trial Principal cautions
Orlistat Oral, three times daily Mean weight loss 5.8 kg versus 3.0 kg with placebo at 4 years, with cumulative diabetes incidence 6.2% versus 9.0%, a risk reduction of 37.3%[41] Steatorrhoea, fat-soluble vitamin malabsorption
Phentermine-topiramate Oral, once daily Weight change at 56 weeks of 7.8% at 7.5/46 mg and 9.8% at 15/92 mg versus 1.2% with placebo[42] Teratogenicity requiring monthly pregnancy testing, contraindicated in cardiovascular disease, paraesthesia, dry mouth[39]
Naltrexone-bupropion Oral, twice daily Modest weight reduction relative to placebo Suicidal ideation warning, hypertension, contraindicated with opioid use[39]
Liraglutide 3.0 mg Subcutaneous, daily Mean weight loss 8.4 kg versus 2.8 kg with placebo at 56 weeks[43] Gastrointestinal intolerance, gallbladder disease, pancreatitis
Semaglutide 2.4 mg Subcutaneous, weekly Mean body weight change -14.9% versus -2.4% with placebo at 68 weeks, treatment difference -12.4 percentage points (95% CI -13.4 to -11.5)[44] Gastrointestinal intolerance, contraindicated with personal or family history of medullary thyroid carcinoma or MEN2
Semaglutide 7.2 mg Subcutaneous, weekly Greater mean weight reduction than the 2.4 mg dose in phase 3b evaluation[45] Dose-related gastrointestinal adverse effects
Oral semaglutide 25 mg Oral, daily Significant weight reduction versus placebo, providing a non-injectable option within the same class[46] As for injectable semaglutide
Tirzepatide Subcutaneous, weekly Mean weight change at 72 weeks of -15.0% at 5 mg, -19.5% at 10 mg and -20.9% at 15 mg versus -3.1% with placebo[47] As for GLP-1 receptor agonists
Orforglipron Oral, daily Mean body weight change at 72 weeks of -7.5% at 6 mg, -8.4% at 12 mg and -11.2% at 36 mg versus -2.1% with placebo[48] Gastrointestinal adverse effects, discontinuation for adverse events in 5.3% to 10.3%
Cagrilintide-semaglutide Subcutaneous, weekly Significantly greater weight reduction than placebo in adults with overweight or obesity, and in those with type 2 diabetes mellitus[49][50] Gastrointestinal adverse effects
Setmelanotide Subcutaneous, daily Substantial weight reduction in LEPR or POMC deficiency[15] Restricted to genetically confirmed melanocortin pathway defects, skin hyperpigmentation

Tirzepatide produced greater weight reduction than semaglutide in the only large head-to-head randomised comparison, with mean reductions of 20.2% versus 13.7% at 72 weeks.[51]

Multi-agonist agents including triple hormone receptor agonists remain investigational and are not approved for clinical use. See Obesity future or investigational therapies.

Complication-Directed Selection

Complication Supporting randomised evidence
Established cardiovascular disease without diabetes Semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% (HR 0.80)[52]
Type 2 diabetes with cardiovascular risk Tirzepatide compared with dulaglutide for cardiovascular outcomes[53]
Heart failure with preserved ejection fraction Semaglutide improved symptoms and physical limitation and reduced weight[54]
Heart failure with preserved ejection fraction and type 2 diabetes Mean change in KCCQ clinical summary score 13.7 versus 6.4 points and body weight -9.8% versus -3.4% with placebo at 52 weeks[55]
Heart failure with preserved ejection fraction (dual agonist) Tirzepatide reduced the risk of worsening heart failure events and improved health status[56]
Obstructive sleep apnoea Tirzepatide significantly reduced the apnoea-hypopnoea index in adults with moderate to severe disease and obesity[57]
Chronic kidney disease in type 2 diabetes Semaglutide reduced the risk of major kidney disease events[58]
Albuminuria in obesity with or without diabetes Tirzepatide reduced urine albumin-to-creatinine ratio without adverse change in eGFR[59]
Metabolic dysfunction-associated steatohepatitis Semaglutide improved liver histology in biopsy-proven disease with fibrosis stage 2 or 3[60]

Safety and Monitoring

  • Gastrointestinal adverse effects predominate with incretin-based agents, are usually mild to moderate, and cluster during dose escalation.[48]
  • Withhold or adjust GLP-1 receptor agonists before elective procedures according to multisociety perioperative guidance, because of concerns regarding delayed gastric emptying and aspiration risk.[61]
  • An association between semaglutide and nonarteritic anterior ischaemic optic neuropathy has been reported in a single-centre retrospective matched cohort, with hazard ratios of 4.28 in type 2 diabetes mellitus and 7.64 in overweight or obesity. The authors state that causality is not established and that further study is required.[62]
  • In a post hoc analysis of three randomised trials in participants without known major psychopathology, tirzepatide was not associated with increased depressive symptoms, and suicidal ideation was reported in 0.6% of participants in each group.[63]
  • If a medication becomes unavailable, switching to another approved agent is recommended, with reassessment when supply is restored.[32]

Procedural / Surgical Therapy

Indications

  • Metabolic and bariatric surgery is recommended for individuals with BMI 35 kg/m2 or greater regardless of the presence or severity of comorbidity, and should be considered for individuals with BMI 30 to 34.9 kg/m2 with metabolic disease. Thresholds are adjusted downward in Asian populations, with surgery considered above BMI 27.5 kg/m2.[64]
  • These criteria supersede the 1991 consensus thresholds that required BMI 40 kg/m2, or 35 kg/m2 with comorbidity.[64]

Procedures

  • Sleeve gastrectomy and Roux-en-Y gastric bypass are the dominant contemporary operations. One anastomosis gastric bypass and biliopancreatic diversion with duodenal switch are performed in selected cases. Adjustable gastric banding has largely been abandoned because of poor durability and high reoperation rates.
  • Endoscopic sleeve gastroplasty is an option for patients with class I or class II obesity who decline or are ineligible for surgery, and produced significantly greater weight loss than lifestyle intervention alone in a randomised trial.[65]

Outcomes

  • Bariatric surgery reduced overall mortality compared with usual care in the first large prospective controlled study.[1]
  • Median life expectancy was longer after bariatric surgery than after usual obesity care in long-term follow-up of the same cohort.[66]
  • In a one-stage meta-analysis of 174,772 participants with 7712 deaths over 1.2 million patient-years, metabolic and bariatric surgery was associated with a 49.2% reduction in the hazard of death and a median life expectancy 6.1 years longer than usual care. The gain was 9.3 years in patients with diabetes and 5.1 years in those without, with numbers needed to treat over 10 years of 8.4 and 29.8 respectively.[67]
  • Surgery was superior to intensive medical therapy for glycaemic control at five years in type 2 diabetes mellitus.[68]
  • Pooled long-term randomised data confirmed superior glycaemic outcomes with surgery compared with medical and lifestyle management.[69]
  • Weight loss after gastric bypass was largely sustained at 12 years, establishing durability well beyond that achievable with lifestyle intervention alone.[70]

Postoperative Care

  • Lifelong micronutrient supplementation and monitoring, including iron, vitamin B12, folate, calcium, vitamin D, and thiamine where vomiting occurs
  • Surveillance for internal hernia, marginal ulceration, dumping syndrome, post-bypass hypoglycaemia, nephrolithiasis and metabolic bone disease
  • Screening for alcohol use disorder and for psychological difficulty after surgery
  • Structured long-term follow-up, since weight regain and recurrence of comorbidity occur in a proportion of patients

Long-Term Management

Obesity requires indefinite management. The evidence on withdrawal is now unambiguous.

  • Withdrawal of semaglutide and lifestyle intervention after 68 weeks resulted in regain of approximately two thirds of the lost weight by week 120, with cardiometabolic improvements reverting toward baseline for most variables.[71]
  • Continued weekly semaglutide maintained weight loss whereas switching to placebo led to regain.[72]
  • In a randomised maintenance trial, weight change from baseline to week 112 was -21.9% with continued maximum tolerated dose tirzepatide, -16.6% with dose reduction to 5 mg and -9.9% with placebo. Rescue therapy for regain of at least half the lost weight was required by 8% on maximum tolerated dose, 25% on 5 mg and 67% on placebo. Dose reduction is therefore a reasonable alternative to discontinuation but is not equivalent to continuation.[73]
  • Continuing obesity medication during the weight maintenance phase carries a strong recommendation.[38]
  • Monitor weight, waist circumference, blood pressure, glycaemia, lipids, renal and hepatic parameters, nutritional adequacy, muscle mass and function, and quality of life at defined intervals.
  • Maintain resistance training and adequate protein intake during and after weight loss to limit loss of lean mass, particularly in older adults.[9]

Special Populations

  • Children and adolescents. Evaluate and treat obesity promptly rather than adopting watchful waiting, using intensive health behaviour and lifestyle treatment as the foundation, with pharmacotherapy and surgery considered in appropriate candidates.[74] Once-weekly semaglutide plus lifestyle intervention produced significantly greater reduction in BMI than placebo in adolescents with obesity.[75]
  • Older adults. Screen for sarcopenic obesity, prioritise preservation of muscle mass and physical function, and pair any weight reduction with resistance training and adequate protein.[9]
  • Pregnancy and preconception. Obesity pharmacotherapy is not recommended in pregnancy. Phentermine-topiramate requires monthly pregnancy testing because of teratogenicity, and contraceptive counselling should accompany any prescription in people who can become pregnant.[39]
  • Perioperative period. Follow multisociety guidance on withholding or adjusting GLP-1 receptor agonists before elective procedures.[61]
  • Type 2 diabetes mellitus. Select agents with demonstrated glycaemic and cardiorenal benefit, and anticipate somewhat smaller weight reduction than in people without diabetes.[76][77]
  • Patients requiring weight-inducing medications. Substitute where clinically possible, and where it is not, proceed with obesity pharmacotherapy, which retains efficacy in this group.[19]
  • Monogenic and syndromic obesity. Refer for genetic confirmation and consider melanocortin-4 receptor agonist therapy in eligible patients.[15]

Treatment Selection Algorithm

 
 
 
 
Confirmed obesity, staged, secondary causes addressed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comprehensive lifestyle and behavioural therapy for all patients, plus treatment of coexisting risk factors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 30 or greater, or BMI 27 or greater with a weight-related complication?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No: continue lifestyle therapy and monitor
 
 
 
Yes: add pharmacotherapy, selecting the agent by complication profile, contraindications, access and patient preference
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reassess response and tolerability at defined intervals
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adequate response: continue therapy indefinitely, consider dose reduction rather than discontinuation
 
 
 
Inadequate response or intolerance: switch agent, or refer for metabolic and bariatric surgery if criteria are met
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-procedure: lifelong nutritional supplementation, monitoring and management of weight recurrence

Case Studies

Case #1

Template:Nutritional pathology Template:Link FA ar:سمنة zh-min-nan:Toā-kho͘ bg:Затлъстяване ca:Obesitat cs:Obezita da:Overvægt de:Adipositas eo:Trodikiĝo eu:Loditasun gl:Obesidade ko:비만증 hi:मेदुरता hr:Pretilost id:Obesitas it:Obesità he:השמנה jv:Obesitas lt:Nutukimas ms:Obesiti nl:Obesitas no:Fedme simple:Obesity sk:Obezita sl:Debelost sr:Гојазност fi:Ylipaino sv:Övervikt ta:உடற் பருமன் th:โรคอ้วน wa:Fornourixhaedje yi:גראב

References

  1. ↑ 1.0 1.1 Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H (2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N Engl J Med. 357 (8): 741–52. doi:10.1056/NEJMoa066254. PMID 17715408.
  2. ↑ 2.0 2.1 Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA (2002). "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin". N Engl J Med. 346 (6): 393–403. doi:10.1056/NEJMoa012512. PMID 11832527.
  3. ↑ 3.0 3.1 Rubino F, Cummings DE, Eckel RH, Cohen RV, Wilding J, Brown WA (2025). "Definition and diagnostic criteria of clinical obesity". Lancet Diabetes Endocrinol. 13 (3): 221–262. doi:10.1016/S2213-8587(24)00316-4. PMID 39824205 Check |pmid= value (help). Vancouver style error: initials (help)
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Gudzune KA, Perreault L, Apovian CM, Aroda VR, Aronne LJ, Fitch A (2026). "Screening, Diagnosis, Evaluation, and Staging of Obesity in Adults: Standards of Care in Overweight and Obesity-2026". BMJ Open Diabetes Res Care. 13 (Suppl 1): e006247. doi:10.1136/bmjdrc-2026-006247. PMID 42242835 Check |pmid= value (help).
  5. ↑ Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA (2013). "2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults". Circulation. 129 (25 Suppl 2): S102–38. doi:10.1161/01.cir.0000437739.71477.ee. PMID 24222017.
  6. ↑ 6.0 6.1 Sharma AM, Kushner RF (2009). "A proposed clinical staging system for obesity". Int J Obes (Lond). doi:10.1038/ijo.2009.2. PMID 19188927.
  7. ↑ Busetto L, Dicker D, Frühbeck G, Halford J, Sbraccia P, Yumuk V (2024). "A new framework for the diagnosis, staging and management of obesity in adults". Nat Med. doi:10.1038/s41591-024-03095-3. PMID 38969880 Check |pmid= value (help). Vancouver style error: initials (help)
  8. ↑ 8.0 8.1 8.2 Nadolsky K, Garvey WT, Agarwal M, Bonnecaze A, Burguera B, Chaplin MD (2025). "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. 31 (11): 1351–1394. doi:10.1016/j.eprac.2025.07.017. PMID 40956256 Check |pmid= value (help).
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Donini LM, Busetto L, Bischoff SC, Cederholm T, Ballesteros-Pomar MD, Batsis JA (2022). "Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement". Obes Facts. 15 (3): 321–335. doi:10.1159/000521241. PMID 35196654 Check |pmid= value (help).
  10. ↑ 10.0 10.1 Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LM (2017). "Obesity Pathogenesis: An Endocrine Society Scientific Statement". Endocr Rev. 38 (4): 267–296. doi:10.1210/er.2017-00111. PMID 28898979.
  11. ↑ 11.0 11.1 Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A (2011). "Long-term persistence of hormonal adaptations to weight loss". N Engl J Med. 365 (17): 1597–604. doi:10.1056/NEJMoa1105816. PMID 22029981.
  12. ↑ 12.0 12.1 Fothergill E, Guo J, Howard L, Kerns JC, Knuth ND, Brychta R (2016). "Persistent metabolic adaptation 6 years after "The Biggest Loser" competition". Obesity (Silver Spring). 24 (8): 1612–9. doi:10.1002/oby.21538. PMID 27136388.
  13. ↑ 13.0 13.1 Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR (2015). "Genetic studies of body mass index yield new insights for obesity biology". Nature. 518 (7538): 197–206. doi:10.1038/nature14177. PMID 25673413.
  14. ↑ 14.0 14.1 14.2 Loos R, Yeo G (2022). "The genetics of obesity: from discovery to biology". Nat Rev Genet. 23 (2): 120–133. doi:10.1038/s41576-021-00414-z. PMID 34556834 Check |pmid= value (help). Vancouver style error: initials (help)
  15. ↑ 15.0 15.1 15.2 Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H (2020). "Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials". Lancet Diabetes Endocrinol. 8 (12): 960–970. doi:10.1016/S2213-8587(20)30364-8. PMID 33137293 Check |pmid= value (help).
  16. ↑ Sattar N, Linetzky B, Ruotolo G, Verma S, Sourij H, Wang H (2026). "Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis". J Am Coll Cardiol. 88 (6): 652–666. doi:10.1016/j.jacc.2026.04.044. PMID 42233927 Check |pmid= value (help).
  17. ↑ 17.0 17.1 Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY (2019). "Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake". Cell Metab. 30 (1): 67–77.e3. doi:10.1016/j.cmet.2019.05.008. PMID 31105044.
  18. ↑ 18.0 18.1 18.2 18.3 Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C (2015). "Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis". J Clin Endocrinol Metab. 100 (2): 363–70. doi:10.1210/jc.2014-3421. PMID 25590213.
  19. ↑ 19.0 19.1 Galindo RJ, Gudzune KA, Look M, Lee CJ, Benabbad I, Cao D (2026). "Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials". JAMA Netw Open. 9 (3): e263274. doi:10.1001/jamanetworkopen.2026.3274. PMID 41885866 Check |pmid= value (help).
  20. ↑ NCD Risk Factor Collaboration (NCD-RisC) (2024). "Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults". Lancet. 403 (10431): 1027–1050. doi:10.1016/S0140-6736(23)02750-2. PMID 38432237 Check |pmid= value (help). Vancouver style error: initials (help)
  21. ↑ GBD 2021 Adult BMI Collaborators (2025). "Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050". Lancet. 405 (10481): 813–838. doi:10.1016/S0140-6736(25)00355-1. PMID 40049186 Check |pmid= value (help). Vancouver style error: initials (help)
  22. ↑ GBD 2021 Child and Adolescent BMI Collaborators (2025). "Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990-2021, with forecasts to 2050". Lancet. 405 (10481): 785–812. doi:10.1016/S0140-6736(25)00397-6. PMID 40049185 Check |pmid= value (help). Vancouver style error: initials (help)
  23. ↑ 23.0 23.1 23.2 23.3 23.4 "Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief No. 508". National Center for Health Statistics. September 2024. Retrieved August 26, 2026.
  24. ↑ 24.0 24.1 "Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Age 20 and Older: United States, 1960-1962 Through August 2021-August 2023. NCHS Health E-Stat 111". National Center for Health Statistics. February 2026. Retrieved August 26, 2026.
  25. ↑ Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C (2019). "Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity". N Engl J Med. 381 (25): 2440–2450. doi:10.1056/NEJMsa1909301. PMID 31851800.
  26. ↑ 26.0 26.1 26.2 26.3 Bannuru RR (2025). "Weight stigma and bias: standards of care in overweight and obesity-2025". BMJ Open Diabetes Res Care. 13 (Suppl 1): e004962. doi:10.1136/bmjdrc-2025-004962. PMID 40379436 Check |pmid= value (help).
  27. ↑ 27.0 27.1 Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW (2018). "Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults: US Preventive Services Task Force Recommendation Statement". JAMA. 320 (11): 1163–1171. doi:10.1001/jama.2018.13022. PMID 30326502.
  28. ↑ Powell-Wiley TM, Poirier P, Burke LE, Després JP, Gordon-Larsen P, Lavie CJ (2021). "Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association". Circulation. 143 (21): e984–e1010. doi:10.1161/CIR.0000000000000973. PMID 33882682 Check |pmid= value (help).
  29. ↑ Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K (2016). "Body Fatness and Cancer--Viewpoint of the IARC Working Group". N Engl J Med. 375 (8): 794–8. doi:10.1056/NEJMsr1606602. PMID 27557308.
  30. ↑ Global BMI Mortality C (2016). "Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents". Lancet. 388 (10046): 776–86. doi:10.1016/S0140-6736(16)30175-1. PMID 27423262. Vancouver style error: missing comma (help)
  31. ↑ Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J (2009). "Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies". Lancet. 373 (9669): 1083–96. doi:10.1016/S0140-6736(09)60318-4. PMID 19299006.
  32. ↑ 32.0 32.1 32.2 32.3 Gudzune KA, Kahan S, Kushner RF, Apovian CM, Aroda VR, Bannuru RR (2026). "Pharmacologic treatment of obesity in adults: Standards of care in overweight and obesity". BMJ Open Diabetes Res Care. 13 (Suppl 1): e005729. doi:10.1136/bmjdrc-2025-005729. PMID 41529914 Check |pmid= value (help).
  33. ↑ Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M (2013). "Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes". N Engl J Med. 369 (2): 145–54. doi:10.1056/NEJMoa1212914. PMID 23796131.
  34. ↑ Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L (2018). "Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial". Lancet. 391 (10120): 541–551. doi:10.1016/S0140-6736(17)33102-1. PMID 29221645.
  35. ↑ Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J, Ioannidis J (2018). "Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial". JAMA. 319 (7): 667–679. doi:10.1001/jama.2018.0245. PMID 29466592. Vancouver style error: initials (help)
  36. ↑ Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F (2018). "Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts". N Engl J Med. 378 (25): e34. doi:10.1056/NEJMoa1800389. PMID 29897866.
  37. ↑ Grunvald E, Shah R, Hernaez R, Chandar AK, Pickett-Blakely O, Teigen LM (2022). "AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity". Gastroenterology. 163 (5): 1198–1225. doi:10.1053/j.gastro.2022.08.045. PMID 36273831 Check |pmid= value (help).
  38. ↑ 38.0 38.1 Alexander L, Purnell JQ, Burridge K, Cornier MA, Golden A, Horn DB (2026). "Joint TOS/OMA/OAC expert guidance statement on the pharmacological management of United States adults with overweight or obesity using the GRADE approach". Obes Pillars. 18: 100254. doi:10.1016/j.obpill.2026.100254. PMID 41859682 Check |pmid= value (help).
  39. ↑ 39.0 39.1 39.2 39.3 Qaseem A, Cross JT, Harrod CS, Owens DK, Balk EM, Crandall CJ (2026). "Pharmacologic Treatments With Lifestyle Modifications in Nonpregnant Adults With Overweight or Obesity in Outpatient Settings: A Living Clinical Guideline From the American College of Physicians". Ann Intern Med. 179 (8): 1177–1185. doi:10.7326/ANNALS-25-02714. PMID 42296496 Check |pmid= value (help).
  40. ↑ Nong K, Wang X, Zeng L, Yao L, Wang Z, Guyatt G (2026). "Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis". BMJ. 394: e372161. doi:10.1136/bmj-2025-372161. PMID 42419792 Check |pmid= value (help).
  41. ↑ Torgerson JS, Hauptman J, Boldrin MN, Sjöström L (2004). "XENical in the prevention of diabetes in obese subjects (XENDOS) study". Diabetes Care. 27 (1): 155–61. doi:10.2337/diacare.27.1.155. PMID 14693982.
  42. ↑ Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML (2011). "Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial". Lancet. 377 (9774): 1341–52. doi:10.1016/S0140-6736(11)60205-5. PMID 21481449.
  43. ↑ Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M (2015). "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management". N Engl J Med. 373 (1): 11–22. doi:10.1056/NEJMoa1411892. PMID 26132939.
  44. ↑ Wilding J, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I (2021). "Once-Weekly Semaglutide in Adults with Overweight or Obesity". N Engl J Med. 384 (11): 989–1002. doi:10.1056/NEJMoa2032183. PMID 33567185 Check |pmid= value (help). Vancouver style error: initials (help)
  45. ↑ Wharton S, Davies M, Garvey WT, Hankosky ER, Kushner RF, Lingvay I (2025). "Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial". Lancet Diabetes Endocrinol. 13 (11): 949–963. doi:10.1016/S2213-8587(25)00231-3. PMID 40961952 Check |pmid= value (help).
  46. ↑ Wharton S, Blüher M, Deerochanawong C, Ekelund M, Garvey WT, Hankosky ER (2025). "Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity". N Engl J Med. 393 (11): 1077–1087. doi:10.1056/NEJMoa2506623. PMID 40934115 Check |pmid= value (help).
  47. ↑ Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B (2022). "Tirzepatide Once Weekly for the Treatment of Obesity". N Engl J Med. 387 (3): 205–216. doi:10.1056/NEJMoa2206038. PMID 35658024 Check |pmid= value (help).
  48. ↑ 48.0 48.1 Wharton S, Aronne LJ, Stefanski A, Alfaris NF, Ciudin A, Yokote K (2025). "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment". N Engl J Med. 393 (18). doi:10.1056/NEJMoa2511774. PMID 40960239 Check |pmid= value (help).
  49. ↑ Garvey WT, Blüher M, Osorto Contreras CK, Davies M, Emmerson C, Hall A (2025). "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity". N Engl J Med. 393 (7): 635–647. doi:10.1056/NEJMoa2502081. PMID 40544433 Check |pmid= value (help).
  50. ↑ Davies MJ, Bajaj HS, Broholm C, Fonseca V, Lingvay I, McCrimmon RJ (2025). "Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes". N Engl J Med. 393 (7): 648–659. doi:10.1056/NEJMoa2502082. PMID 40544432 Check |pmid= value (help).
  51. ↑ Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E (2025). "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity". N Engl J Med. 393 (1): 26–36. doi:10.1056/NEJMoa2416394. PMID 40353578 Check |pmid= value (help).
  52. ↑ Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S (2023). "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes". N Engl J Med. 389 (24): 2221–2232. doi:10.1056/NEJMoa2307563. PMID 37952131 Check |pmid= value (help).
  53. ↑ Nicholls SJ, Nissen SE, Buse JB, Linnebjerg H, Wiese RJ, Ahmad NN (2025). "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes". N Engl J Med. 393 (24): 2409–2420. doi:10.1056/NEJMoa2509750. PMID 41406444 Check |pmid= value (help).
  54. ↑ Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M (2023). "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity". N Engl J Med. 389 (12): 1069–1084. doi:10.1056/NEJMoa2306963. PMID 37622681 Check |pmid= value (help).
  55. ↑ Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK (2024). "Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes". N Engl J Med. 390 (15): 1394–1407. doi:10.1056/NEJMoa2313917. PMID 38587233 Check |pmid= value (help).
  56. ↑ Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V (2025). "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity". N Engl J Med. 392 (5): 427–437. doi:10.1056/NEJMoa2410027. PMID 39555826 Check |pmid= value (help).
  57. ↑ Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A (2024). "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity". N Engl J Med. 391 (13): 1193–1205. doi:10.1056/NEJMoa2404881. PMID 38912654 Check |pmid= value (help).
  58. ↑ Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann J, Bakris G (2024). "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes". N Engl J Med. 391 (2): 109–121. doi:10.1056/NEJMoa2403347. PMID 38785209 Check |pmid= value (help). Vancouver style error: initials (help)
  59. ↑ Heerspink H, Friedman AN, Bjornstad P, van Raalte DH, Cherney D, Cao D (2025). "Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes". J Am Soc Nephrol. 36 (11): 2190–2200. doi:10.1681/ASN.0000000764. PMID 40512543 Check |pmid= value (help). Vancouver style error: initials (help)
  60. ↑ Sanyal AJ, Newsome PN, Kliers I, Østergaard LH, Long MT, Kjær MS (2025). "Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis". N Engl J Med. doi:10.1056/NEJMoa2413258. PMID 40305708 Check |pmid= value (help).
  61. ↑ 61.0 61.1 Kindel TL, Wang AY, Wadhwa A, Schulman AR, Sharaiha RZ, Kroh M (2024). "Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period". Clin Gastroenterol Hepatol. 23 (12): 2083–2085. doi:10.1016/j.cgh.2024.10.003. PMID 39480373 Check |pmid= value (help).
  62. ↑ Hathaway JT, Shah MP, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW (2024). "Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide". JAMA Ophthalmol. 142 (8): 732–739. doi:10.1001/jamaophthalmol.2024.2296. PMID 38958939 Check |pmid= value (help).
  63. ↑ Wadden TA, Oquendo MA, Kushner RF, Cao D, Karanikas CA, Kechter A (2026). "Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT". Obesity (Silver Spring). 34 (3): 565–578. doi:10.1002/oby.70122. PMID 41537305 Check |pmid= value (help).
  64. ↑ 64.0 64.1 Eisenberg D, Shikora SA, Aarts E, Aminian A, Angrisani L, Cohen RV (2023). "2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Indications for Metabolic and Bariatric Surgery". Obes Surg. 33 (1): 3–14. doi:10.1007/s11695-022-06332-1. PMID 36336720 Check |pmid= value (help).
  65. ↑ Abu Dayyeh BK, Bazerbachi F, Vargas EJ, Sharaiha RZ, Thompson CC, Thaemert BC (2022). "Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial". Lancet. doi:10.1016/S0140-6736(22)01280-6. PMID 35908555 Check |pmid= value (help).
  66. ↑ Carlsson L, Sjöholm K, Jacobson P, Andersson-Assarsson JC, Svensson PA, Taube M (2020). "Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study". N Engl J Med. 383 (16): 1535–1543. doi:10.1056/NEJMoa2002449. PMID 33053284 Check |pmid= value (help). Vancouver style error: initials (help)
  67. ↑ Syn NL, Cummings DE, Wang LZ, Lin DJ, Zhao JJ, Loh M (2021). "Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants". Lancet. 397 (10287): 1830–1841. doi:10.1016/S0140-6736(21)00591-2. PMID 33965067 Check |pmid= value (help).
  68. ↑ Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA (2017). "Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes". N Engl J Med. 376 (7): 641–651. doi:10.1056/NEJMoa1600869. PMID 28199805.
  69. ↑ Courcoulas AP, Patti ME, Hu B, Arterburn DE, Simonson DC, Gourash WF (2024). "Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes". JAMA. 331 (8): 654–664. doi:10.1001/jama.2024.0318. PMID 38411644 Check |pmid= value (help).
  70. ↑ Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN (2017). "Weight and Metabolic Outcomes 12 Years after Gastric Bypass". N Engl J Med. 377 (12): 1143–1155. doi:10.1056/NEJMoa1700459. PMID 28930514.
  71. ↑ Wilding J, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K (2022). "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension". Diabetes Obes Metab. 24 (8): 1553–1564. doi:10.1111/dom.14725. PMID 35441470 Check |pmid= value (help). Vancouver style error: initials (help)
  72. ↑ Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C (2021). "Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial". JAMA. 325 (14): 1414–1425. doi:10.1001/jama.2021.3224. PMID 33755728 Check |pmid= value (help).
  73. ↑ Horn DB, Aronne LJ, Wharton S, Bays HE, le Roux CW, Srinath R (2026). "Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial". Lancet. 407 (10545): 2305–2318. doi:10.1016/S0140-6736(26)00656-2. PMID 42119587 Check |pmid= value (help).
  74. ↑ Hampl SE, Hassink SG, Skinner AC, Armstrong SC, Barlow SE, Bolling CF (2023). "Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity". Pediatrics. 151 (2). doi:10.1542/peds.2022-060640. PMID 36622115 Check |pmid= value (help).
  75. ↑ Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK (2022). "Once-Weekly Semaglutide in Adolescents with Obesity". N Engl J Med. 387 (24): 2245–2257. doi:10.1056/NEJMoa2208601. PMID 36322838 Check |pmid= value (help).
  76. ↑ Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D (2023). "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial". Lancet. 402 (10402): 613–626. doi:10.1016/S0140-6736(23)01200-X. PMID 37385275 Check |pmid= value (help).
  77. ↑ Lingvay I, Bauer R, Baker-Knight J, Bue-Valleskey J, Deroover L, Garvey WT (2025). "Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial". Lancet Diabetes Endocrinol. 13 (11): 935–948. doi:10.1016/S2213-8587(25)00232-5. PMID 40961953 Check |pmid= value (help).

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Obesity&oldid=1745856"