Obesity and Weight Loss
Conventional Obesity Management
A National Institutes of Health panel established recommendations for the treatment of obesity based on BMI, waist circumference, and overall disease risk (Expert Treatment Panel 1998). The Panel recommends low-calorie or very-low calorie diets as the cornerstone of any weight-loss strategy, such as to create a deficit of 500-1000 calories/day and a weight loss of 1-2 lb/week. Lifestyle modification and weight loss are the recommended methods for lowering blood pressure and blood lipids (LDL, total cholesterol, and triglycerides) in overweight/obese individuals, and for lowering blood glucose in overweight type 2 diabetes patients. The panel further recommends 30-45 minutes of moderate physical activity, 3-5 days per week, to promote weight loss and decrease abdominal fat.
Weight loss drugs may be incorporated into the weight loss plan for obese individuals (BMI ≥30) with no other risk factors or obesity-related diseases (eg, hypertension, heart disease, diabetes), or for overweight individuals with a BMI of ≥27 and obesity-related risk factors or diseases. Weight loss surgery is reserved for class III obese individuals (BMI ≥40), or class II individuals (BMI ≥35) at high risk of obesity-associated mortality and when non-invasive methods have failed (Expert Treatment Panel 1998; Mayo Clinic 2012).
The drugs in this section are FDA-approved for the treatment of obesity.
Orlistat. While pharmaceutical approaches to obesity have traditionally addressed appetite suppression, orlistat (Alli®, Xenical®) works by decreasing fat absorption from the gut. It binds and inactivates pancreatic lipase, the enzyme responsible for breaking down dietary triglycerides into fatty acids so they can be absorbed through the intestinal wall (Xiao 2012).
Sixteen trials have observed orlistat’s effects in over 10 000 subjects, and have shown an average annual weight loss of 6.4 pounds when used over 12 months. It has been shown to reduce the incidence of diabetes, lower total & LDL cholesterol and blood pressure, and improve blood sugar control in patients with diabetes, while only slightly lowering HDL (good) cholesterol concentrations (Rucker 2007). The most common side effects of orlistat include diarrhea, flatulence, bloating, abdominal pain, and indigestion (Ioannides-Demos 2011). Although rare, serious liver damage has been reported from orlistat usage (Garber 2012). Life Extension suggests taking fat-soluble nutrients such as vitamin D, vitamin E, vitamin K, lutein, zeaxanthin, and fish oil at the time of the day furthest from the last orlistat dose, since it may impair their absorption.
Lorcaserin. Lorcaserin is a selective serotonin receptor agonist, specifically the 5-HT2C receptor, enhancing the satiating effects of serotonin in the central nervous system. Lorcaserin acts more selectively on serotonin receptors than the fenfluramine anti-obesity drugs that were introduced in the 1970s and withdrawn in 1997 due to increased risk of cardiac valvular disease. Lorcaserin acts on the 5-HT2C receptor, showing roughly 100-fold greater selectivity for the 5-HT2C receptor than the 5-HT2B receptor, and demonstrated no increase in the rate of valvular disease after 2 years of treatment (Ioannides-Demos 2011).
In 2 Phase III trials, lorcaserin treatment of 6380 non-diabetic patients aged 18-66 years with a BMI of 27–45 for 1 year resulted in a 5.8% weight loss, compared to 2.5% with placebo (Ioannides-Demos 2011). Lorcaserin was approved by the FDA in June 2012 under the brand name Belviq®, making it the first anti-obesity drug to be approved since orlistat in 1999 (Healy 2012). The most frequent side effects for lorcaserin are headache, dizziness, and nausea. Also, there may be some potential for abuse due to the drug’s hallucinogenic properties; the Drug Enforcement Administration (DEA) has thus proposed regulating lorcaserin as a schedule IV substance (Houck 2012).
Phentermine/topiramate. Topiramate is an approved anti-epileptic drug with appetite-suppressant activity; phentermine is an amphetamine that has been available in the United States as a short-term prescription weight-loss treatment. The combination has been investigated as an anti-obesity therapy; in a 28-week randomized trial, phentermine plus topiramate (92 mg/15 mg and 46 mg/7.5 mg doses) demonstrated a 9.2% weight loss compared to a 6.4% weight loss with topiramate alone, 6.1% for phentermine alone, and 1.7% for placebo (Ioannides-Demos 2011).
Phentermine/topiramate was approved by the FDA under the brand name Qsymia® in July 2012 (Gann 2012). The combination is also in clinical development for sleep apnea syndrome and type 2 diabetes (Cameron 2012). Potential side effects include depression and cognitive complaints, potential cardiovascular risk, and an increase in heart rate (Hiatt 2012).
Bariatric surgical procedures modify the size or course of the gastrointestinal tract to attenuate the appetite. Five bariatric procedures have been developed, although the 2 most common (Roux-en-Y gastric bypass and Laproscopic gastric band) represented about 49% and 42% of procedures in the United States in 2008, respectively. Gastric bypass reduces the stomach to a small pouch and bypasses part of the small intestine. The laproscopic gastric band fits around the upper part of the stomach, also creating a smaller stomach pouch that limits food consumption. A newer procedure, sleeve gastrectomy, is increasing in popularity; it only removes part of the stomach, but leaves its connection to the intestines intact (Dixon 2012).
Bariatric procedures reduce hunger and caloric intake, and have resulted in average weight losses of 20-35%, depending on surgical technique. They have also been shown to affect food preferences by a yet unknown mechanism; gastric banding usually limits consumption of breads and pasta, and gastric bypass reduces intake of sweet and fatty foods and possibly increases vegetable consumption. Several studies of bariatric surgery in diabetic patients have demonstrated a reduction in high blood sugar levels and insulin resistance, and reduced the need for blood sugar-lowering medications. Most of these procedures are permanent, require lifelong follow-up, and are not without surgical risk. Because they dramatically alter gastrointestinal anatomy and physiology, they can also lead to malabsorption and deficiency of certain nutrients (particularly vitamin B12, iron, folate, calcium, vitamin D, zinc, and copper) (Dixon 2012).