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.	史轶蘩, 李光伟, 朱禧星, 等. 奥利司他在中国肥胖患者中的疗效和安全性分析. 中华医学会第六次全国内分泌学术会议论文汇编, 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.	Lindgärde 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.	韩英, 江平, 王治伟, 等. 奥利司他对肥胖IGT人群糖尿病预防效果. 广东药学, 2004, 14(3): 40-41.
34.	钱端, 柯元南, 王云, 等. 赛尼可在肥胖合并高血压患者中的临床应用. 中日友好医院学报, 2002, 16(1): 28-29.
35.	王艳军, 刘聪, 刘英敏. 奥利司他辅助治疗肥胖2型糖尿病32例. 中国新药与临床杂志, 2003, 22(11): 651-653.
36.	叶世伟, 尚惺杰, 黎红光. 奥利司他联合二甲双胍治疗肥胖并发高血压24例. 医药导报, 2006, 25(9): 886-887.
37.	张可. 奥利司他干预治疗肥胖并糖耐量减低的疗效观察. 中原医刊, 2007, 34(17): 74-75.
38.	Sahebkar A, Simental-Mendía LE, Reiner Ž, 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. 史轶蘩, 李光伟, 朱禧星, 等. 奥利司他在中国肥胖患者中的疗效和安全性分析. 中华医学会第六次全国内分泌学术会议论文汇编, 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. Lindgärde 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. 韩英, 江平, 王治伟, 等. 奥利司他对肥胖IGT人群糖尿病预防效果. 广东药学, 2004, 14(3): 40-41.
34. 钱端, 柯元南, 王云, 等. 赛尼可在肥胖合并高血压患者中的临床应用. 中日友好医院学报, 2002, 16(1): 28-29.
35. 王艳军, 刘聪, 刘英敏. 奥利司他辅助治疗肥胖2型糖尿病32例. 中国新药与临床杂志, 2003, 22(11): 651-653.
36. 叶世伟, 尚惺杰, 黎红光. 奥利司他联合二甲双胍治疗肥胖并发高血压24例. 医药导报, 2006, 25(9): 886-887.
37. 张可. 奥利司他干预治疗肥胖并糖耐量减低的疗效观察. 中原医刊, 2007, 34(17): 74-75.
38. Sahebkar A, Simental-Mendía LE, Reiner Ž, 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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