Efficacy of Orlistat versus Placebo in the Improvement of Lipid Profile Among Overweight and Obese...
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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
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Transcript of Efficacy of Orlistat versus Placebo in the Improvement of Lipid Profile Among Overweight and Obese...
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
Page 2
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
Page 3
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
Page 4
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
Page 5
Author Duration P BMI WEIGHT AGE % M TC LDL HDL TG COMORBIDLitonjua, et al 2004
14 wk ^~ O: 300P: 286
O:30.83 ±4.53P:30.37 ±4.38
O:77.45 ±13.87P:75.82 ±14.22
O:38.79 ±10.37P:39.98 ±10.52
O:33.3P:29
O:6.26 ±0.92P:6.33 ±0.9
O:4.35 ±0.82P:4.35 ±0.75
O:1.19 ±0.31P:1.23 ±0.35
O:1.7 ±0.88P:1.71 ±0.99
Metabolic Syndrome
Lindgarde, et al 2000
1y*^~ O: 190P: 186
O:33.2 ±3P:33.2 ±3.1
O:96.1 ±13.7P:95.9 ±13.5
O:53.7 ±9.4P:53.3 ±9.9
O:34.7P38.2
O:6.15 ±1.21P:6.06 ±1.19
O:3.75 ±1.38P:3.66 ±1.41
NR NR Type 2 diabetesHypertension
Kelley, et al 2002
1y^~ O: 266P: 269
O:35.8 ±3.26P:35.6 ±4.92
O:102 ±16.31P101.8 ±116.4
O:57.8 ±8.15P:58 ±8.2
O:43.6P43.9
O:5.49 ±0.07P:5.43 ±0.07
O:3.37 ±0.06P:3.3 ±0.06
O:1.07 ±0.02P:1.07 ±0.02
O:2.33 ±0.1P:2.31 ±0.08
Diabetes, treated with insulin
Finer, et al 2000
48wk**^~
O: 110P: 108
O: 36.8 ±3.6P:36.8 ±3.7
O: 97.9 ±12.9P: 98.4 ±15
O: 41.5 ±10.5P: 41.4 ±10
O:10.9P:12
O:5.64 ±0.95P:5.62 ±0.95
O:3.67 ±0.84P: 3.67 ±0.85
O:1.22 ±0.28P:1.22 ±0.29
NR None
Muls, et al 2001
24wk*^~ O: 147P: 143
O:32.9 ±3.5P:33.0 ±3.7
O:88.9 ±13.6P:89.8 ±14.4
O:49.6 ±10P:47.5 ±11
O:18.4P:20.3
O:7.33 ±0.74P:7.28 ±0.77
O:5.09 ±0.61P:5.03 ±0.68
O:1.45 ±0.35P:1.49 ±0.37
O:1.71 ±0.68P:1.65 ±0.62
None
Hollander, et al 1998
1y***^~ O:162P:159
O:34.5 ±3.2P:34 ±3.4
O:99.6 ±14.5P:99.7 ±15.4
O:55.4 ±8.8P:54.7 ±9.7
O:48.8P:53.5
NR NR NR NR Type 2 diabetes
Hill, et al 1999
1y****^~
O: 87P: 102
O:32.8 ±0.2P: 32.8 ±0.2
O: 89.7 0.9P: 90.8 0.9
O: 45.9 0.7P: 46.4 0.7
NR NR NR NR NR None
Page 6
Total Cholesterol
Study or Subgroup
Finer et al, 1999Hill et al, 1999Hollander, 1998Kelley et al, 2002Lingarde,2000Litonjua et al, 2004Muls et al, 2001
Total (95% CI)
Heterogeneity: Tau² = 0.02; Chi² = 791.39, df = 6 (P < 0.00001); I² = 99%Test for overall effect: Z = 5.63 (P < 0.00001)
Mean
-0.05-0.47-0.08
-0.3-0.24-0.48-0.42
SD
0.760.070.050.070.830.880.75
Total
11487
162266190300128
1247
Mean
0.3-0.350.390.08
-0.09-0.160.14
SD
0.680.080.060.070.820.920.85
Total
114102159276186286127
1250
Weight
11.8%16.9%17.0%17.0%12.6%13.4%11.4%
100.0%
IV, Random, 95% CI
-0.35 [-0.54, -0.16]-0.12 [-0.14, -0.10]-0.47 [-0.48, -0.46]-0.38 [-0.39, -0.37]-0.15 [-0.32, 0.02]
-0.32 [-0.47, -0.17]-0.56 [-0.76, -0.36]
-0.33 [-0.45, -0.22]
Experimental Control Mean Difference Mean DifferenceIV, Random, 95% CI
-1 -0.5 0 0.5 1Favours experimental Favours control
Page 7
Low Density Lipoprotein
Study or Subgroup
Finer et al, 1999Hill et al, 1999Hollander, 1998Kelley et al, 2002Lingarde,2000Litonjua et al, 2004Muls et al, 2001
Total (95% CI)
Heterogeneity: Tau² = 0.01; Chi² = 526.33, df = 6 (P < 0.00001); I² = 99%Test for overall effect: Z = 6.21 (P < 0.00001)
Mean
-0.11-0.29-0.13-0.38-0.25-0.51-0.53
SD
0.630.070.050.051.120.880.65
Total
11487
162266190300128
1247
Mean
0.21-0.210.22
-0.08-0.07-0.2
-0.09
SD
0.530.070.060.050.980.910.8
Total
114102159276186286127
1250
Weight
12.0%18.6%18.8%18.8%
8.9%12.4%10.5%
100.0%
IV, Random, 95% CI
-0.32 [-0.47, -0.17]-0.08 [-0.10, -0.06]-0.35 [-0.36, -0.34]-0.30 [-0.31, -0.29]-0.18 [-0.39, 0.03]
-0.31 [-0.46, -0.16]-0.44 [-0.62, -0.26]
-0.28 [-0.36, -0.19]
Experimental Control Mean Difference Mean DifferenceIV, Random, 95% CI
-2 -1 0 1 2Favours experimental Favours control
Page 8
High Density Lipoprotein
Study or Subgroup
Finer et al, 1999Hill et al, 1999Hollander, 1998Kelley et al, 2002Lingarde,2000Muls et al, 2001
Total (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 7.52, df = 4 (P = 0.11); I² = 47%Test for overall effect: Z = 4.42 (P < 0.00001)
Mean
0.15-0.03
00.02
00.07
SD
0.230.07
00.010.220.22
Total
11487
162266190128
947
Mean
0.160.01
00.050.020.17
SD
0.210.07
00.01
0.20.24
Total
114102159276186127
964
Weight
6.4%27.2%
49.4%10.5%
6.5%
100.0%
IV, Random, 95% CI
-0.01 [-0.07, 0.05]-0.04 [-0.06, -0.02]
Not estimable-0.03 [-0.03, -0.03]-0.02 [-0.06, 0.02]
-0.10 [-0.16, -0.04]
-0.03 [-0.05, -0.02]
Experimental Control Mean Difference Mean DifferenceIV, Random, 95% CI
-2 -1 0 1 2Favours experimental Favours control
Page 9
Triglyceride
Study or Subgroup
Hill et al, 1999Hollander, 1998Kelley et al, 2002Lingarde,2000Muls et al, 2001
Total (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 81.49, df = 4 (P < 0.00001); I² = 95%Test for overall effect: Z = 3.92 (P < 0.0001)
Mean
-0.27-0.010.18
-0.040.08
SD
0.060.070.161.160.72
Total
87162266190128
833
Mean
-0.150.210.31
-0.150.14
SD
0.070.080.130.930.55
Total
102159276186127
850
Weight
27.7%27.8%27.2%
6.9%10.5%
100.0%
IV, Random, 95% CI
-0.12 [-0.14, -0.10]-0.22 [-0.24, -0.20]-0.13 [-0.15, -0.11]
0.11 [-0.10, 0.32]-0.06 [-0.22, 0.10]
-0.13 [-0.19, -0.06]
Experimental Control Mean Difference Mean DifferenceIV, Random, 95% CI
-2 -1 0 1 2Favours experimental Favours control
Page 10
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
Page 11
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
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
Page 13
1. Subjects were randomly allocated to groups (in a crossover study, subjects were randomly allocated an order in which treatments were received)
2. Allocation was concealed3. The groups were similar at baseline regarding the most important prognostic indicators4. There was blinding of all subjects5. There was blinding of all therapists who administered the therapy6. There was blinding of all assessors who measured at least one key outcome7. Measures of at least one key outcome were obtained from more than 85% of the subjects
initially allocated to groups8. 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”
9. The results of between-group statistical comparisons are reported for at least one key outcome
10. 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
Page 14
Physiotherapy Evidence Database (PEDro) scale
Criteria 1 2 3 4 5 6 7 8 9 10 Eligibility Score
Finer, et al6 1 0 1 1 1 1 1 1 1 1 √ 9
Hill, et al7 1 0 0 1 1 0 0 1 1 1 √ 6
Hollander, et al8 1 0 1 1 1 0 1 1 1 1 √ 8
Kelley, et al9 1 0 1 1 0 0 1 1 1 1 √ 7
Lindgarde, et al10 1 0 1 1 1 0 1 1 1 1 √ 8
Litonjua, et al11 1 0 1 1 1 0 0 1 1 1 √ 7
Muls, et al12 1 0 1 1 1 0 1 1 1 1 √ 8
