Chandy Lou P. Malong, MD & John S. Delgado, MD Efficacy of Orlistat versus Placebo in the Improvement of Lipid Profile Among Overweight and Obese Patients: A Meta-analysis Chandy Lou P. Malong, MD & John S. Delgado, MD 1

Introduction increase of 4.5% in hypercholesterolemia from the previous prevalence rate of 4% (6th National Nutrition Health Survey 2003-04) inhibitor of pancreatic, gastric, and carboxylesterlipase blocks absorption of cholesterol and triacylglycerols systemic effect facilitates weight loss in obese subjects weight loss in overweight persons associated with an improvement in the serum lipid profile Pi-Sunyer FX. A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity. Clin Ther 1996;18:1006-1035 Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord 1992;6:397-415

Objectives To determine, through a meta-analysis, the efficacy of Orlistat compared with placebo in lowering lipid levels among overweight and obese patients with or without other comorbidities

Methodology MEDLINE, HERDIN, Cochrane, ScienceDirect, Manual searching RCTs: Orlistat 120mg/tab TID vs Placebo on Lipid Profile among Overweight and Obese reported as Mean Change from Baseline 58 Journals to 7 RCTs PEDro Rating Scale REVMAN 5.0: mean change in TC, LDL-C, HDL-C, and TG

Author Duration P BMI WEIGHT AGE % M TC LDL HDL TG COMORBID Litonjua, et al 2004 14 wk ^~ O: 300 P: 286 O:30.83 ±4.53 P:30.37 ±4.38 O:77.45 ±13.87 P:75.82 ±14.22 O:38.79 ±10.37 P:39.98 ±10.52 O:33.3 P:29 O:6.26 ±0.92 P:6.33 ±0.9 O:4.35 ±0.82 P:4.35 ±0.75 O:1.19 ±0.31 P:1.23 ±0.35 O:1.7 ±0.88 P:1.71 ±0.99 Metabolic Syndrome Lindgarde, et al 2000 1y*^~ O: 190 P: 186 O:33.2 ±3 P:33.2 ±3.1 O:96.1 ±13.7 P:95.9 ±13.5 O:53.7 ±9.4 P:53.3 ±9.9 O:34.7 P38.2 O:6.15 ±1.21 P:6.06 ±1.19 O:3.75 ±1.38 P:3.66 ±1.41 NR Type 2 diabetes Hypertension Kelley, et al 2002 1y^~ O: 266 P: 269 O:35.8 ±3.26 P:35.6 ±4.92 O:102 ±16.31 P101.8 ±116.4 O:57.8 ±8.15 P:58 ±8.2 O:43.6 P43.9 O:5.49 ±0.07 P:5.43 ±0.07 O:3.37 ±0.06 P:3.3 ±0.06 O:1.07 ±0.02 P:1.07 ±0.02 O:2.33 ±0.1 P:2.31 ±0.08 Diabetes, treated with insulin Finer, et al 2000 48wk**^~ O: 110 P: 108 O: 36.8 ±3.6 P:36.8 ±3.7 O: 97.9 ±12.9 P: 98.4 ±15 O: 41.5 ±10.5 P: 41.4 ±10 O:10.9 P:12 O:5.64 ±0.95 P:5.62 ±0.95 O:3.67 ±0.84 P: 3.67 ±0.85 O:1.22 ±0.28 P:1.22 ±0.29 None Muls, et al 2001 24wk*^~ O: 147 P: 143 O:32.9 ±3.5 P:33.0 ±3.7 O:88.9 ±13.6 P:89.8 ±14.4 O:49.6 ±10 P:47.5 ±11 O:18.4 P:20.3 O:7.33 ±0.74 P:7.28 ±0.77 O:5.09 ±0.61 P:5.03 ±0.68 O:1.45 ±0.35 P:1.49 ±0.37 O:1.71 ±0.68 P:1.65 ±0.62 Hollander, et al 1998 1y***^~ O:162 P:159 O:34.5 ±3.2 P:34 ±3.4 O:99.6 ±14.5 P:99.7 ±15.4 O:55.4 ±8.8 P:54.7 ±9.7 O:48.8 P:53.5 Hill, et al 1999 1y****^~ O: 87 P: 102 O:32.8 ±0.2 P: 32.8 ±0.2 O: 89.7 ± 0.9 P: 90.8 ± 0.9 O: 45.9 ± 0.7 P: 46.4 ± 0.7

Total Cholesterol

Low Density Lipoprotein

High Density Lipoprotein

Triglyceride

Discussion Cholesterol is absorbed by becoming incorporated into mixed micelles Inhibition of fat digestion prevents micelle formation, and therefore, cholesterol absorption Majority of the indication for Orlistat use is for weight reduction. Most studies show improvement in other cardiovascular risk factors different from body weight, including lipid profile No statistically significant change in HDL-C level Factors that may have an effect on HDL: duration of the Orlistat treatment change in initial HDL-C was observed only during the active weight loss Smoking

Conclusion Impact to Clinical Practice Orlistat produces statistically significant improvement in TC, LDL-C, TG levels in overweight and obese patients This study has established the lipid-lowering effect of Orlistat with the known benefits of weight reduction. Orlistat can be indicated for the treatment of hypercholesterolemia, hyper-LDLipidemia, and hypertriglyceridemia in addition to obesity management Impact to Research Effect of Orlistat in improving Lipid Profile independent of weight loss Whether Orlistat can be used as an adjunct to standard lipid-lowering agents particularly among high risk patients

Chandy Lou P. Malong, MD & John S. Delgado, MD Efficacy of Orlistat versus Placebo in the Improvement of Lipid Profile Among Overweight and Obese Patients: A Meta-analysis Chandy Lou P. Malong, MD & John S. Delgado, MD 12

Physiotherapy Evidence Database (PEDro) scale Subjects were randomly allocated to groups (in a crossover study, subjects were randomly allocated an order in which treatments were received) Allocation was concealed The groups were similar at baseline regarding the most important prognostic indicators There was blinding of all subjects There was blinding of all therapists who administered the therapy There was blinding of all assessors who measured at least one key outcome Measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated to groups All subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analyzed by “intention to treat” The results of between-group statistical comparisons are reported for at least one key outcome The study provides both point measures and measures of variability for at least one key outcome **Eligibility criteria were specified

Physiotherapy Evidence Database (PEDro) scale Criteria 1 2 3 4 5 6 7 8 9 10 Eligibility Score Finer, et al6 √ Hill, et al7 Hollander, et al8 Kelley, et al9 Lindgarde, et al10 Litonjua, et al11 Muls, et al12