Efficacy and safety of Orlistat for obese patients with cardiovascular risk: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

GAO Le ¹ , LIU Jingbo ¹ , YANG Jun ¹ , YANG Jichun ¹ , ZHANG Yan ¹ , CHEN Jing ² , ZHENG Liying ² , LU Jing ³ , HAN Sheng ² ,  SUN Feng ¹

1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, P.R.China;
2. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, P.R.China;
3. Department of Clinical Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding?author：

SUN Feng, Email: sunfeng@bjmu.edu.cn

Keywords：

Orlistat; Obese patient; Cardiovascular risk factor; Hypertension; Diabetes; Prediabetes; Hyperlipemia; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201707107

Video：

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ObjectivesTo systematically review the efficacy and safety of Orlistat for obese patients with cardiovascular risk including hyperlipidemia, hypertension, diabetes and prediabetes.MethodsSinomed, CNKI, WanFang Data, PubMed, EMbase, The Cochrane Library and ClinicalTrails.gov databases were electronically searched to collect randomized controlled trials (RCTs) of Orlistat for obese patients with cardiovascular risk such as hyperlipemia, diabetes, prediabetes and hypertension from inception to Jan 7^th, 2017. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using Stata 14.0 software.ResultsA total of 28 RCTs were included. The results of meta-analysis showed that, compared with placebo, Orlistat could significantly reduce the weight (MD=–2.85, 95%CI –3.47 to –2.24, P=0.000), waist (MD=–2.45, 95%CI –3.07 to –1.83, P=0.000) and BMI (MD=–1.29, 95%CI –2.08 to –0.49, P=0.002) of patients. Orlistat could also control the blood pressure, blood glucose and other cardiovascular risk factors well. Compared with the blank control, Orlistat could improve the waist and parts of cardiovascular risk factors (P<0.05). The incidence of adverse events of Orlistat was slightly higher than that of placebo, but most could be self-healing.ConclusionsCurrent evidence shows that compared with placebo and blank control, Orlistat is effective for improving both weight loss and some cardiovascular risk factors. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

Citation： GAO Le, LIU Jingbo, YANG Jun, YANG Jichun, ZHANG Yan, CHEN Jing, ZHENG Liying, LU Jing, HAN Sheng, SUN Feng. Efficacy and safety of Orlistat for obese patients with cardiovascular risk: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2018, 18(5): 476-488. doi: 10.7507/1672-2531.201707107 Copy

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2.	Poirier P, Després JP. Exercise in weight management of obesity. Cardiol Clin, 2001, 19(3): 459-470.
3.	Leung WY, Thomas GN, Chan JC, et al. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther, 2003, 25(1): 58-80.
4.	Guerciolini R. Mode of action of orlistat. Int J Obes Relat Metab Disord, 1997, 21(Suppl 3): S12-S23.
5.	史軼蘩, 李光偉, 朱禧星, 等. 奧利司他在中國肥胖患者中的療效和安全性分析. 中華醫學會第六次全國內分泌學術會議論文匯編, 2001.
6.	Sjostrom L, Rissanen A, Andersen T, et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Ter Arkh, 2000, 72(8): 50-54.
7.	Phelan S, Wadden TA. Combining behavioral and pharmacological treatments for obesity. Obes Res, 2002, 10(6): 560-574.
8.	Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA, 1999, 281(3): 235-242.
9.	Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0(updated March 2011). Available at: www.cochrane-handbook.org.
10.	Bakris G, Calhoun D, Egan B, et al. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens, 2002, 20(11): 2257-2267.
11.	Bergholm R, Tiikkainen M, Vehkavaara S, et al. Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes. Diabetes Care, 2003, 26(6): 1667-1672.
12.	Berne C, Orlistat Swedish Type 2 diabetes Study Group. A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin. Diabet Med, 2005, 22(5): 612-618.
13.	Bloch KV, Salles GF, Muxfeldt ES, et al. Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial. J Hypertens, 2003, 21(11): 2159-2165.
14.	Borges RL, Ribeiro-Filho FF, Carvalho KM, et al. Impact of weight loss on adipocytokines, C-reactive protein and insulin sensitivity in hypertensive women with central obesity. Arq Bras Cardiol, 2007, 89(6): 409-414.
15.	Cocco G, Pandolfi S, Rousson V. Sufficient weight reduction decreases cardiovascular complications in diabetic patients with the metabolic syndrome. Heart Drug, 2005, 5(2): 68-74.
16.	de Castro JJ, Dias T, Chambel P, et al. A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia. Rev Port Cardiol, 2009, 28(12): 1361-1374.
17.	Derosa G, Cicero AF, D’Angelo A, et al. Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. J Clin Pharm Ther, 2012, 37(2): 187-195.
18.	Didangelos TP, Thanopoulou AK, Bousboulas SH, et al. The orlistat and cardiovascular risk profile in patients with metabolic syndrome and type 2 diabetes (orlicardia) study. Curr Med Res Opin, 2004, 20(9): 1393-1401.
19.	Dixon AN, Valsamakis G, Hanif MW, et al. Effect of the orlistat on serum endotoxin lipopolysaccharide and adipocytokines in South Asian individuals with impaired glucose tolerance. Int J Clin Pract, 2008, 62(7): 1124-1129.
20.	Guy-Grand B, Drouin P, Eschwège E, et al. Effects of orlistat on obesity-related diseases-a six-month randomized trial. Diabetes Obes Metab, 2004, 6(5): 375-383.
21.	Hanefeld M, Sachse G. The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes Metab, 2002, 4(6): 415-423.
22.	Kelley DE, Bray GA, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care, 2002, 25(6): 1033-1041.
23.	Kelley DE, Kuller LH, McKolanis TM, et al. Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. Diabetes Care, 2004, 27(1): 33-40.
24.	Kopelman P, Groot Gde H, Rissanen A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring), 2010, 18(1): 108-115.
25.	Lindg?rde F. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. J Intern Med, 2000, 248(3): 245-254.
26.	Martin J, Paquette C, Marceau S, et al. Impact of orlistat-induced weight loss on diastolic function and heart rate variability in severely obese subjects with diabetes. J Obes, 2011, 2011: 394658.
27.	Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care, 2002, 25(7): 1123-1128.
28.	Muls E, Kolanowski J, Scheen A, et al. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes Relat Metab Disord, 2001, 25(11): 1713-1721.
29.	Nakou ES, Filippatos TD, Georgoula M, et al. The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia. Curr Med Res Opin, 2008, 24(7): 1919-1929.
30.	Shi YF, Pan CY, Hill J, et al. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes. Diabet Med, 2005, 22(12): 1737-1743.
31.	Suyog J, Milind P, Karuna R. Comparison of efficacy and safety of rimonabant with orlistat in obese and overweight patients. Intern J Pharm Bio Scienc, 2011, 2: 179-187.
32.	Swinburn BA, Carey D, Hills AP, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab, 2005, 7(3): 254-262.
33.	韓英, 江平, 王治偉, 等. 奧利司他對肥胖IGT人群糖尿病預防效果. 廣東藥學, 2004, 14(3): 40-41.
34.	錢端, 柯元南, 王云, 等. 賽尼可在肥胖合并高血壓患者中的臨床應用. 中日友好醫院學報, 2002, 16(1): 28-29.
35.	王艷軍, 劉聰, 劉英敏. 奧利司他輔助治療肥胖2型糖尿病32例. 中國新藥與臨床雜志, 2003, 22(11): 651-653.
36.	葉世偉, 尚惺杰, 黎紅光. 奧利司他聯合二甲雙胍治療肥胖并發高血壓24例. 醫藥導報, 2006, 25(9): 886-887.
37.	張可. 奧利司他干預治療肥胖并糖耐量減低的療效觀察. 中原醫刊, 2007, 34(17): 74-75.
38.	Sahebkar A, Simental-Mendía LE, Reiner ?, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacol Res, 2017, 122: 53-65.
39.	Aldekhail NM, Logue J, McLoone P, et al. Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Obes Rev, 2015, 16(12): 1071-1080.
40.	Narayanaswami V, Dwoskin LP. Obesity: Current and potential pharmacotherapeutics and targets. Pharmacol Ther, 2017, 170: 116-147.
41.	Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA, 2016, 315(22): 2424-2434.
42.	Cunningham JW, Wiviott SD. Modern obesity pharmacotherapy: weighing cardiovascular risk and benefit. Clin Cardiol, 2014, 37(11): 693-699.
43.	Vorsanger MH, Subramanyam P, Weintraub HS, et al. Cardiovascular effects of the new weight loss agents. J Am Coll Cardiol, 2016, 68(8): 849-859.

1. WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser, 2000, 894: 1-253.
2. Poirier P, Després JP. Exercise in weight management of obesity. Cardiol Clin, 2001, 19(3): 459-470.
3. Leung WY, Thomas GN, Chan JC, et al. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther, 2003, 25(1): 58-80.
4. Guerciolini R. Mode of action of orlistat. Int J Obes Relat Metab Disord, 1997, 21(Suppl 3): S12-S23.
5. 史軼蘩, 李光偉, 朱禧星, 等. 奧利司他在中國肥胖患者中的療效和安全性分析. 中華醫學會第六次全國內分泌學術會議論文匯編, 2001.
6. Sjostrom L, Rissanen A, Andersen T, et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Ter Arkh, 2000, 72(8): 50-54.
7. Phelan S, Wadden TA. Combining behavioral and pharmacological treatments for obesity. Obes Res, 2002, 10(6): 560-574.
8. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA, 1999, 281(3): 235-242.
9. Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0(updated March 2011). Available at: www.cochrane-handbook.org.
10. Bakris G, Calhoun D, Egan B, et al. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens, 2002, 20(11): 2257-2267.
11. Bergholm R, Tiikkainen M, Vehkavaara S, et al. Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes. Diabetes Care, 2003, 26(6): 1667-1672.
12. Berne C, Orlistat Swedish Type 2 diabetes Study Group. A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin. Diabet Med, 2005, 22(5): 612-618.
13. Bloch KV, Salles GF, Muxfeldt ES, et al. Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial. J Hypertens, 2003, 21(11): 2159-2165.
14. Borges RL, Ribeiro-Filho FF, Carvalho KM, et al. Impact of weight loss on adipocytokines, C-reactive protein and insulin sensitivity in hypertensive women with central obesity. Arq Bras Cardiol, 2007, 89(6): 409-414.
15. Cocco G, Pandolfi S, Rousson V. Sufficient weight reduction decreases cardiovascular complications in diabetic patients with the metabolic syndrome. Heart Drug, 2005, 5(2): 68-74.
16. de Castro JJ, Dias T, Chambel P, et al. A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia. Rev Port Cardiol, 2009, 28(12): 1361-1374.
17. Derosa G, Cicero AF, D’Angelo A, et al. Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. J Clin Pharm Ther, 2012, 37(2): 187-195.
18. Didangelos TP, Thanopoulou AK, Bousboulas SH, et al. The orlistat and cardiovascular risk profile in patients with metabolic syndrome and type 2 diabetes (orlicardia) study. Curr Med Res Opin, 2004, 20(9): 1393-1401.
19. Dixon AN, Valsamakis G, Hanif MW, et al. Effect of the orlistat on serum endotoxin lipopolysaccharide and adipocytokines in South Asian individuals with impaired glucose tolerance. Int J Clin Pract, 2008, 62(7): 1124-1129.
20. Guy-Grand B, Drouin P, Eschwège E, et al. Effects of orlistat on obesity-related diseases-a six-month randomized trial. Diabetes Obes Metab, 2004, 6(5): 375-383.
21. Hanefeld M, Sachse G. The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes Metab, 2002, 4(6): 415-423.
22. Kelley DE, Bray GA, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care, 2002, 25(6): 1033-1041.
23. Kelley DE, Kuller LH, McKolanis TM, et al. Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. Diabetes Care, 2004, 27(1): 33-40.
24. Kopelman P, Groot Gde H, Rissanen A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring), 2010, 18(1): 108-115.
25. Lindg?rde F. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. J Intern Med, 2000, 248(3): 245-254.
26. Martin J, Paquette C, Marceau S, et al. Impact of orlistat-induced weight loss on diastolic function and heart rate variability in severely obese subjects with diabetes. J Obes, 2011, 2011: 394658.
27. Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care, 2002, 25(7): 1123-1128.
28. Muls E, Kolanowski J, Scheen A, et al. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes Relat Metab Disord, 2001, 25(11): 1713-1721.
29. Nakou ES, Filippatos TD, Georgoula M, et al. The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia. Curr Med Res Opin, 2008, 24(7): 1919-1929.
30. Shi YF, Pan CY, Hill J, et al. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes. Diabet Med, 2005, 22(12): 1737-1743.
31. Suyog J, Milind P, Karuna R. Comparison of efficacy and safety of rimonabant with orlistat in obese and overweight patients. Intern J Pharm Bio Scienc, 2011, 2: 179-187.
32. Swinburn BA, Carey D, Hills AP, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab, 2005, 7(3): 254-262.
33. 韓英, 江平, 王治偉, 等. 奧利司他對肥胖IGT人群糖尿病預防效果. 廣東藥學, 2004, 14(3): 40-41.
34. 錢端, 柯元南, 王云, 等. 賽尼可在肥胖合并高血壓患者中的臨床應用. 中日友好醫院學報, 2002, 16(1): 28-29.
35. 王艷軍, 劉聰, 劉英敏. 奧利司他輔助治療肥胖2型糖尿病32例. 中國新藥與臨床雜志, 2003, 22(11): 651-653.
36. 葉世偉, 尚惺杰, 黎紅光. 奧利司他聯合二甲雙胍治療肥胖并發高血壓24例. 醫藥導報, 2006, 25(9): 886-887.
37. 張可. 奧利司他干預治療肥胖并糖耐量減低的療效觀察. 中原醫刊, 2007, 34(17): 74-75.
38. Sahebkar A, Simental-Mendía LE, Reiner ?, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacol Res, 2017, 122: 53-65.
39. Aldekhail NM, Logue J, McLoone P, et al. Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Obes Rev, 2015, 16(12): 1071-1080.
40. Narayanaswami V, Dwoskin LP. Obesity: Current and potential pharmacotherapeutics and targets. Pharmacol Ther, 2017, 170: 116-147.
41. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA, 2016, 315(22): 2424-2434.
42. Cunningham JW, Wiviott SD. Modern obesity pharmacotherapy: weighing cardiovascular risk and benefit. Clin Cardiol, 2014, 37(11): 693-699.
43. Vorsanger MH, Subramanyam P, Weintraub HS, et al. Cardiovascular effects of the new weight loss agents. J Am Coll Cardiol, 2016, 68(8): 849-859.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of Orlistat for obese patients with cardiovascular risk: a meta-analysis

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