As obesity becomes a growing pandemic in the United States, the need for weight-loss methods is ever-growing.  In the United States, 66% of adults aged 20 years or older are defined as either overweight with a BMI of 25-29.9kg/m2 or are defined as obese with a BMI of ≥30kg/m2.1  Furthermore, in the United States, obesity has doubled over the past 30 years and has manifested in about 32% of the population becoming obese.1  An issue that is not confined within the United States, the World Health Organization estimates that over 400 million people worldwide are considered obese and about 1.6 million people are overweight.2  The conditions of being overweight and obese can lead to serious major health issues: stroke, coronary artery disease, type-2 diabetes, heart failure, hypertension, reproductive and gastrointestinal cancers, dyslipidemia, gallstones, sleap apnea, fatty liver disease and osteoarthritis.

            There have been a few FDA-approved pharmacotherapy options for long-term weight-management like Orlistat 120mg (Xenical), Sibutramine (Meridia, Reductil), and Rimonabant (Accomplia).3  In addition, there are pharmacotherapy options for short-term weight management: Benzphetamine (Bontril), Diethlyproprion (Tenuate, Tepanil), Phendrimetrazine, and Phentermine.3  However, these pharmacotherapy options for weight-management are all prescription-based and require proper recommendation from doctors.  In a sudden change in the weight-management drug market, “in February 2007, orlistat 60 mg (Alli, manufactured by GlaxoSmithKline Consumer Healthcare) was approved by the Food and Drug Administration as an OTC weight loss aid for overweight adults ≥18 years, and is currently available in the OTC market.”1            

 

Uses:
Alli contributes to weight loss along with a low-fat diet. Alli also appears to reverse fatty infiltration and improve hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH).5  Patients with NASH have as much as 50-80% of liver weight made up of fat compared to the less than 5% liver mass composing of fat in normal patients.  Patients with NASH are at an increased risk to develop fibrosis, cirrhosis, and hepatocellular carcinoma.  NASH has symptoms of obesity, diabetes mellitus type 2, and hyperlipdemia.
            Alli is indicated for overweight individuals 18 years of age or older with body mass index values of 27.0 or greater.

How it is used:
Alli is administered in a blue capsule by mouth with liquid. Users are advised to take one pills one hour after each meal (usually three times a day). Also, users are advised to ingest meals that contain no more than 30% of calories from fat. Users usually take a daily multivitamin as a supplement.

How it works:
Orlistat is a reversible lipase inhibitor. Its therapeutic activity is exerted in the lumen of the stomach and the small intestine by forming covalent bonds with the active serine residue sites of pancreatic and gastric lipases, and therefore, it reduces intestinal digestion of fat.  Orlistat prevents the lipases from hydrolyzing dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides.  In fact, Orlistat 60mg (Alli) leads to the excretion of around 25% of ingested fat in fecal matter within 24-48 hours of drug-intake; 83% of excreted Orlistat is found to be intact drug in feces.5  Therefore, the absorption of Orlistat is minimal in healthy adult and overweight adult patients.  When Orlistat 60 mg (Alli) is used in conjunction with a hypocaloric diet and moderate exercise, it has proven to be an effective pharmacotherapy option for weight management.

Side Effects

Though the drug is generally safe, there are still side-effects that need to be communicated to consumers.  Most of the side effects are gastrointestinal symptoms that usually occur within the first year of continuous intake, and decrease markedly in the second year.5 Common gastrointestinal side effects include oily spotting, flatus with discharge, decal urgency, fatty stool, oily evacuation, increased defection, fecal incontinence.  These gastrointestinal adverse effects can be attributed directly to Orlistat’s mechanism of action: decreased fat digestion which leads to increased fat excretion.  However, 50% of the adverse episodes cleared within one week and the majority lasted less than four weeks.  To a lesser extent, other symptoms affecting the respiratory system, musculoskeletal system, central nervous system, skin and appendages, reproductive system, urinary system, and psychiatric disorders have been reported.

            Another major adverse effect of taking Orlistat is the decreased levels of fat-soluble vitamins like A, D, E, K, which can be attributed to the deceased fat intake by the intestine.5  Therefore, people using orlistat should take fat-soluble vitamin supplements to return the levels of these vitamins back to normal amounts.  In addition, orlistat has no effect on the pharmacokinetics and pharmacodynamics of alcohol, digoxin, glyburide, nifedipine, oral contraceptives, phenytoin, pravastatin, or warfarin.

 

Sources:

1Drew, Belinda, Dixon A, and Dixon J. "Obesity managment: update on orlistat." Vascular Health Risk Management 3(2007): 817-821.

 

 

 

 

 

 

 

 

2Schwartz, Susan M., Bansal, V, Hale C, Rossi M, and Engle J. "Compliance, Behavior Change, and Weight Loss With Orlistat in an Over-the-Counter Setting." Obesity 16(2007): 623-329.

3Bray, George A., Ryan D.. "Drug Treatment of Overweight Patients." Gastroenterology 132(2007): 2239-2252.

4Hussein, Osamah, Grasovski M, Schlesinger S, Szvalb S, and Assy N. "Orlistat Reverse Fatty Infiltration and Improves Hepatic Fibrosis." Digestive Diseases Sciences 52(2007): 2512-2519.

5"Xenical." 16 Mar 2007. Roche Laboratories Inc.. 5 March 2009. <http://www.rocheusa.com/products/xenical/pi.pdf>.