Pathophysiology and Management of Obesity

People who are overweight or obese account for more than two thirds of the U.S. population and are overrepresented in primary care practices. Some professional organizations now classify obesity, defined as a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or higher, as a disease. A new Review Article explains.

Clinical Pearls

Q: Do lifestyle interventions for weight management need to include in-person counseling to be effective?

A: Lifestyle interventions designed to modify eating behaviors and physical activity are the first option for weight management, given their low cost and the minimal risk of complications. Extensive research led to current recommendations that patients receive high-intensity behavioral counseling, with 14 or more visits in 6 months. A comprehensive program, delivered by a trained interventionist, results in a mean weight loss of 5 to 8%, and approximately 60 to 65% of patients lose 5% or more of initial weight. Telephone-delivered lifestyle interventions result in approximately the same weight loss as in-person counseling, thus encouraging the development of weight-management call centers. Web-based interventions that include personalized interventionist feedback can be prescribed but typically result in only one half to two thirds of the weight loss achieved with in-person counseling. Web-based interventions, however, potentially have greater reach and convenience and lower costs than in-person counseling.

Q: Are the weight loss medications that are FDA-approved for long-term use widely prescribed?

A: The five medications approved for long-term weight management include three single drugs (orlistat, lorcaserin, and liraglutide) and two combination drugs (phentermine–topiramate and naltrexone–bupropion). For a number of reasons, physicians do not use weight-loss medications to the extent that one might expect, given the scale of the obesity problem. First, patients are often disappointed by moderate weight loss. Dissatisfaction with the results, coupled with requirements to pay a substantial portion of costs, may lead to short-term rather than long-term use. Also, some practitioners appear to have lingering concerns about medication safety and may be awaiting the outcome of FDA-mandated cardiovascular disease trials. Finally, weight regain is common after termination of drug treatment, and is discouraging to patients and practitioners. Long-term use of weight-loss medications, as approved by the FDA, may be necessary for long-term weight management, just as medications for hypertension, dyslipidemia, and type 2 diabetes must be administered for the long term.

Table 2. (10.1056/NEJMra1514009/T2) Medications Approved by the Food and Drug Administration for Long-Term Weight Management.

Morning Report Questions

Q: What are the three main types of bariatric surgery used in the United States?

A: In the United States, three main types of bariatric surgery are currently performed; a fourth procedure, biliopancreatic diversion, is performed in no more than 2% of cases. Laparoscopic adjustable gastric banding, the least invasive and safest procedure, involves placing an inflatable silicone band around the gastric fundus to create a small (approximately 30-ml) pouch. This restrictive procedure is reversible and does not cause anatomical gut changes. Roux-en-Y gastric bypass restricts food intake by creating in the upper gastric fundus a small (<50-ml) pouch anastomosed to a Roux limb of jejunum. Food bypasses 95% of the stomach, duodenum, and most of the jejunum. The recently introduced vertical-sleeve gastrectomy involves removal of approximately 70% of the stomach, with subsequent acceleration of gastric emptying. Patients regain an average of 5 to 10% from their lowest weight at 10 years of follow-up, with a higher frequency of full weight regain reported with gastric banding than with the other two operations. Concerns about efficacy and high reoperation rates have led to a decrease in the use of gastric banding in the United States, which accounted for only 6% of procedures in 2013, as compared with vertical-sleeve gastrectomy and Roux-en-Y gastric bypass, which accounted for 49% and 43% of procedures, respectively.

Q: What clinically meaningful improvements are associated with moderate weight loss?

A: Moderate weight loss, defined as a 5 to 10% reduction in baseline weight, is associated with clinically meaningful improvements in obesity-related metabolic risk factors and coexisting disorders. A 5% weight loss improves pancreatic β-cell function and the sensitivity of liver and skeletal muscle to insulin; a larger relative weight loss leads to graded improvements in key adipose-tissue disturbances. Mean losses of 16 to 32% of baseline weight produced by bariatric surgery in patients with severe obesity may lead to disease remission, including remission of type 2 diabetes in patients who undergo bariatric surgery, particularly Roux-en-Y gastric bypass. Significant reductions in all-cause mortality have also been shown in observational studies of surgically treated patients.

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