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Key Clinical Updates in Obesity

Semaglutide, a GLP-1 receptor agonist, is FDA-approved for the treatment of obesity.

Wilding JPH et al. N Engl J Med. [PMID: 33567185]


  • Disorder of energy homeostasis; BMI ≥ 30.

  • Central obesity (abdomen and flank) is a greater health risk than excess weight in the lower body (buttocks and thighs).

  • Associated comorbid conditions include type 2 diabetes mellitus, hypertension, hyperlipidemia, heart disease, stroke, and obstructive sleep apnea.


Obesity is a multifactorial, chronic disease characterized by an accumulation of visceral and subcutaneous fat, which promotes adipocyte dysfunction. Obesity predisposes to a wide variety of comorbid conditions. BMI typically correlates with excess adipose tissue but does not reflect body composition. It is calculated by dividing body weight in kilograms by height in meters squared (kg/m2) (eTable 29–8). The National Institutes of Health defines a normal BMI as 18.5–24.9. Overweight is defined as BMI 25–29.9. Class I obesity is 30–34.9, class II is 35–39.9, and class III is 40 and above. Central obesity (excess adipose tissue around the waist and flank) is a greater health risk than lower body obesity (adipose tissue in the thighs and buttocks). Patients with obesity and increased abdominal circumference (greater than 102 cm or 40 inches in men and 88 cm or 35 inches in women) or high waist–hip ratios (greater than 1.0 in men and 0.85 in women) have a greater risk of weight-related comorbid conditions and early death than patients with the same BMI and lower ratios. Visceral fat within the abdominal cavity is more hazardous to health than subcutaneous fat around the abdomen. Over 40% of Americans have obesity.


Obesity is associated with significant increases in both morbidity and mortality, and many disorders occur with greater frequency in patients with obesity (eFigure 29–1). Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and many cancers. Over 200 health conditions ranging from hypertension and CAD to thromboembolic and skin disorders are more prevalent in patients with obesity. Patients with higher BMI have increased surgical and obstetric risks and higher rates of major depression and binge-eating disorder. Most patients with excess weight have experienced weight bias.

eFigure 29–1.

Role of obesity in the pathophysiology of weight-related diseases. Short arrows refer to a change in the indicated parameter, and long arrows indicate a consequence of that change. In some cases, evidence is epidemiologic; in others, it is experimental. (Modified from Bray GA. Pathophysiology of obesity. Am J Clin Nutr. 1992;55:488S.)


Both genetic and environmental factors contribute to the development of obesity. Twin studies demonstrate that genetics account for 40–90% of variation in BMI, although ...

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