This article is the first in a 4-part series on the Endocrine Society’s clinical practice guideline on the pharmacological management of obesity. This section presents an overview of the topic and the rationale for use of pharmacotherapy for chronic weight management.
The task force stated that obesity is a disease and suggested that modest weight loss (ie, 5% to 10% of body weight) achieved through lifestyle changes and medications can significantly lower the risk for obesity-related conditions and improve physical functioning. Healthy eating, with a focus on portion control, daily physical activity, and behavior modification are recommended for all adults with a body mass index (BMI) ≥25 kg/m2.
Key Recommendation on Pharmacotherapy for Chronic Weight Management
Use of adjunctive pharmacotherapy can produce even greater weight loss and metabolic improvements over nutrition and physical activity alone. Thus, the task force recommends use of pharmacotherapy for chronic weight management as an adjunct to nutrition and physical activity in adults with a BMI ≥27 kg/m2, with an obesity-related comorbidity (eg, hypertension, dyslipidemia, type 2 diabetes, or obstructive sleep apnea) or a BMI >30 kg/m2, and who meet the criteria for use listed on a given agent’s package insert.
These BMI cut points, the task force acknowledged, are necessary to provide implementable recommendations, but are arbitrary with only low-quality evidence supporting the association between these cut points and the incidence of death and cardiovascular disease.
Rationale for Use of Pharmacotherapy for Chronic Weight Management
Adaptive biological responses that promote weight gain in response to weight loss makes sustained weight reduction challenging for most people with obesity. Weight loss is typically associated with a decrease in resting energy expenditure that is out of proportion with changes in lean body mass.
Obesity also is associated with hormone dysregulation. For example, nearly all people with obesity have high levels of leptin, which is responsible for feelings of satiety, and inability to respond to exogenous leptin. Following weight loss, increased feelings of hunger and decreased satiety are linked to an increase in the 24-hour profile of circulating levels of the “hunger hormone” ghrelin, and decreases in the appetite suppressant hormones leptin, peptide YY, cholecystokinin, and insulin. These hormone changes have been shown to persist at least 1 year after weight loss, and may persist indefinitely.
The guidelines note that medications approved for chronic weight management may improve adherence to behavior modifications by 1) lowering appetite (all approved agents except orlistat); or 2) blocking fat and calorie absorption (orlisat only). By amplifying adherence to behavior changes and allowing people to lose weight, these agents may improve physical functioning and allow for greater physical activity.
These medications have each been found to be effective when used as adjunctive treatment along with better nutrition, physical activity, and behavioral modifications, but have not been studied on their own. The mechanism of action of these medications is described in Part 3 of this series. Part 2 of this series will provide an overview of the clinical approach to patients with overweight or obesity.
June 6, 2015
Read other sections of the clinical practice guideline summary:
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.