Orlistat (Xenical) and Sibutramine (Meridia) Small Benefit at High Price: Eleven orlistat weight loss studies (four of which reported a second year ) and five sibutramine studies (three weight loss and two second year) were included in a meta-analysis. Dropouts averaged 33% during the weight loss phase for orlistat and 43% for sibutramine. All received lifestyle modification. Compared to placebo, orlistat-treated patients lost 6 pound or 2.9% more weight than placebo and those on sibutramine lost 9 pound or 4.6%. The numbers achieving 10% or greater weight loss were 12% higher with orlistat and 15% higher with sibutramine. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine caused small increases in blood pressure and pulse rate. Both were modestly effective, but with high dropout rates. Long-term health effects are unknown. Long-term pharmacotherapy for obesity and overweight. Padwal R, Li S, Lau D. Toronto, Ontario. Cochrane Database Syst Rev. 2004;3:CD004. Ed: The costs of these medicines are $1700 and $3000 per year. Since patients regain most of the weight shortly after stopping the medications, these medicines compare poorly with surgery. 

Orlistat (Xenical) Helped Lose a Little Weight: In a 6-month DB PC study of 1,004 obese patients, orlistat 120 mg three times daily plus a mildly reduced-calorie diet produced a significantly greater weight loss than placebo and diet in type 2 diabetes (-4.2% vs. -1.4%), hypertension (-6.2% vs. -1.9%) and hypercholesterolaemia (-5.5% vs. -2.3%) groups (p < 0.0001 for all). Effects of orlistat on obesity-related diseases - a six-month randomized trial. Guy-Grand B, Drouin P, Eschwege E, Gin H, Joubert JM, Valensi P. Paris, France. Diabetes Obes Metab. 2004 Sep;6(5):375-83. Ed: These are modest 4-8 pound weight losses.

Orlistat (Xenical) Very Expensive Way to Lose 6 Pounds: Orlistat is a reversible lipase inhibitor binding to pancreatic and gastric lipases, preventing the breakdown of some triglycerides and lowering fat absorption by 30%. A huge 3,305-patient DB PC 4-year study of obesity (BMI>30) found that those assigned to orlistat 120 mg t.i.d. for 4 years lost 6 more pounds and one out of every 31 avoided developing diabetes (6.2% on orlistat vs. 9.0% on placebo).  The study was funded by the manufacturer. All had a lifestyle modification program. Torgerson, Diabetes Care. 2003;27:33-40, 155-161. Ed: At $130/month for orlistat, $6240 per patient was spend on pills.  This equates to $1000 per pound kept of for four year and $192,000 for each case of diabetes prevented.  Hoffman-La Roche didn't bother to find out what happens when patients stop taking Xenical.  It is a safe bet that they quickly regain the 6 pounds.  If this is true, it means $2,500 per pound to keep the weight off for 10 years!  An English study calculated that $92,000 of treatment of orlistat was necessary to gain one Quality Adjusted Year of Life. Such an outcome is quite unfavorable compared to many other medical treatments of disease. Somewhere between $10,000 and $50,000 is considered acceptable. Obes Rev. 2000 Oct;1(2):121-6.

Orlistat Helped by Statin: In a meta-analysis of 23 DB PC studies of orlistat, orlistat was found of value for losing weight. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. A systematic review of the clinical effectiveness of orlistat used for the management of obesity. O'Meara S, Riemsma R, Shirran L, Mather L, ter Riet G. Obes Rev. 2004 Feb;5(1):51-68. Orlistat is a inhibitor of the thioesterase domain of fatty acid synthase.

Orlistat Weight Loss 9 Pounds in European Study: A 2-year European DB PC study found a mean decrease in body weight of 10.2% (10.3 kg) in the orlistat group compared to 6.1% (6.1 kg) in the placebo group at 1 year. Orlistat for the long-term treatment of obesity. Harp JB. Obes Rev. 2004 Feb;5(1):51-68

Orlistat Weight Loss 8 Pounds in Large European Study: In an 18-month, 696 patient DB PC study, weight loss with orlistat 120 mg t.i.d. was 6.5 kg vs. 3.0 kg. with placebo. Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity. Krempf M, Louvet JP, Allanic H, Miloradovich T, Joubert JM, Attali JR. Obes Rev. 2004 Feb;5(1):43-50

Orlistat Weight Loss 4% in Large Study: In a 1-year 628-patient European DB PC study, those on orlistat lost 8% of their body weight vs. 4% with placebo. Blood pressure also dropped 2 mmHg diastolic more with orlistat. Effect of orlistat-induced weight loss on blood pressure and heart rate in obese patients with hypertension. Sharma AM, Golay A. J Hypertens. 2002 Sep;20(9):1873-8

Orlistat Weight Loss 5.5 Pounds for Diabetics: In a 1-year DB PC study of diabetics, weight loss with orlistat was 3.8 kg vs. 1.3 kg. with placebo. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial. Kelley DE, Bray GA, Pi-Sunyer FX, Klein S, Hill J, Miles J, Hollander P. Diabetes Care. 2002 Jun;25(6):1033-41

Orlistat Weight Loss 3 Pounds in Sweden: In a 1-year 376-patient DB PC study, weight loss was 5.9% with orlistat vs. 4.6% with placebo. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. Lindgarde F. J Intern Med. 2000 Sep;248(3):245-54. Ed: Another reason I don't like orlistat, besides its high cost and very limited effectiveness, is that it partially blocks the absorption of healthy fats as well as unhealthy ones.  A diet including a frequent intake of nuts has been repeatedly associated with longer life as well as weight loss. Orlistat would block this benefit. 

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com

Email: [email protected]