Treatment for Obesity

Educational Objectives

The goal of this program is to improve the management of diabetes. After hearing and assimilating this program, the clinician will better be able to:

1. Offer the appropriate treatment (eg, lifestyle modification, medications, surgery) to patients who are obese.

Summary

Lifestyle intervention

Lifestyle intervention alone is inadequate in producing and maintaining weight loss, because eating processed foods seems to somehow disrupt the signaling pathways, even early in life. Children today may already have inflammation in the hypothalamus, which creates a vicious cycle that causes them to continue to crave unhealthy food.

Obesity is a disease

The American Medical Association has recently defined obesity as a disease. Research in rodents has shown that a high fat diet causes inflammation peripherally and in the hypothalamus (the energy regulation center). This inflammation disrupts the signaling pathways from the gut to the brain, preventing the brain from detecting how much fat is stored and resulting in overeating. Sugar is suspected of being the main culprit causing the hypothalamic inflammation.

Medications for weight loss

Weight loss with current medications:

• Topiramate/phentermine (Qsymia), 8% to 9%

• Lorcaserin (Belviq), ≈5%

• Liraglutide (Victoza; a diabetes drug), 6% to 7%

• Bupropion/naltrexone (Contrave), 6% to 7% (not yet approved by FDA)

Studies in which a higher dose of liraglutide (3 mg) is used for obesity than is used for diabetes (1.2 or 1.8 mg) show greater weight loss.

Recommendations for overweight and obese patients

All patients with a body mass index (BMI) ≥25 kg/m2 should be given a diet and exercise program. Some patients who do not yet have hypothalamic inflammation may benefit from an adjustment in diet and increased physical activity.

For most patients, when weight is lost with diet and exercise, less leptin is produced. Less leptin going to the brain signals hunger, making it difficult to maintain weight loss.

Spiegelman et al (2012) discovered that muscle produces the hormone irisin during exercise. Irisin acts on white fat, converting it to brown fat. This explains why exercise is important for weight maintenance. Exercise probably increases brown fat, allowing more energy to be burned.

Exercise and metformin

Recent data show that metformin blunts the beneficial effects of exercise. Metformin increases adenosine monophosphate-activated protein (AMP) kinase, but it decreases adenosine-5′-triphosphate (ATP), which damages mitochondria. This reduces oxygen consumption during exercise.

Studies by Ruderman et al show that AMP kinase levels are higher after dieting and after bariatric surgery. They also are higher in lean vs obese people. Metformin increases AMP kinase levels, which is beneficial. However, metformin reduces the ability of the body to exercise efficiently.

Primary care providers should probably not recommend exercise to patients taking metformin, especially if the patient has not been exercising.

Candidates for weight loss medications

According to guidelines from the National Heart, Lung, and Blood Institute, patients are candidates for prescription weight loss medications if they have a BMI ≥30 or a BMI ≥27 with a serious condition (eg, diabetes, sleep apnea) and they have already tried diet and exercise alone for 6 months.

In addition to the weight loss medications listed above, some older medications are still available (eg, phentermine, orlistat). Even newer drugs, one of which works on fatty acid oxidation, are in development.

Now that obesity is defined as a disease, third-party payers, most notably Medicare and Medicaid, may start reimbursing for office visits related to treatment of obesity and for weight loss medications.

New devices for obesity

New devices for obesity are also under investigation:

Endoluminal barrier: This is a sleeve that is endoscopically placed into the duodenum. It remains in place for 1 year. It simulates bariatric surgery, changing the gut hormone milieu to some extent, but does not result in as great a weight loss or resolution of type 2 diabetes.

Aspire device: This is a gastrostomy (G) tube that is placed endoscopically in the stomach. The tube connects the stomach to a port on the outside of the abdomen below the rib cage. Contents of the stomach can be extruded by the patient through the port 20 minutes after eating a meal.

Ports are becoming more common for a variety of purposes, including potentially delivering insulin. The technology is improving, resulting in less dislodgment of ports. They must be kept clean to avoid infection.

Bariatric surgery

Bariatric surgery is indicated for patients with a BMI ≥40 or ≥35 with ≥1 serious conditions.

Patients with a BMI ≥30 and a serious health condition may be candidates for laparoscopic adjustable gastric band (Lap-Band), which is less invasive than the Roux-en-Y gastric bypass procedure. The Lap-Band is less effective for weight loss (18% to 20% at best, vs 32% with Roux-en-Y gastric bypass and 25% with gastric sleeve.) and cardiometabolic parameters and is associated with higher reoperation and complication rates.

The Roux-en-Y gastric bypass is the gold standard. More aggressive and invasive procedures include biliopancreatic diversion. Sleeve gastrectomy, which involves removing most of the greater curvature of the stomach and leaving a gastric sleeve, is supplanting Lap-Band.

Treatment gap

There is a treatment gap for patients with a BMI of 30 to 40. Medications are available, but they result in only 5% to 10% weight loss. Better treatment strategies are needed for these patients. In the future, this may involve a combination of medications and new devices to achieve greater weight loss.

Readings

Basu S et al: The relationship of sugar to population-level diabetes prevalence: an econometric analysis of repeated cross-sectional data. PLoS One. 2013;8:e57873; Bostrom P et al: A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463-8; Hinkle W et al: Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans. PLoS One. 2013;8:e59114; Lee D et al: Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity. Am J Physiol Endocrinol Metab. 2013;304:E1245-50; Lustig RH: Fructose: it’s “alcohol without the buzz.” Adv Nutr. 2013;4:226-35; Malin SK et al: Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012;35:131-6; Malin SK et al: Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). 2013;21:93-100.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following was disclosed: Dr. Apovian and the members of the planning committee reported nothing to disclose.

A=Advisory panel B=Speakers bureau C=Consultant G=Grant or other research support 

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

DI041601

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.