Long-term pharmacotherapy for obesity and overweight
Editorial Group: Cochrane Metabolic and Endocrine Disorders Group
Published Online: 20 OCT 2003
Assessed as up-to-date: 23 DEC 2006
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Padwal RS, Rucker D, Li SK, Curioni C, Lau DCW. Long-term pharmacotherapy for obesity and overweight. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD004094. DOI: 10.1002/14651858.CD004094.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 20 OCT 2003
Obesity is a highly and increasingly prevalent chronic condition for which drugs are commonly prescribed to improve health.
To assess the long-term effects of approved anti-obesity medications in clinical trials of at least one-year duration.
MEDLINE, EMBASE, The Cochrane Library, the Current Science Meta-register of Controlled Trials and reference lists were searched. Drug manufacturers and two obesity experts were contacted.
Double-blind, randomised placebo-controlled trials of approved anti-obesity agents that 1) included patients over 18 years, 2) used an intention-to-treat analysis, and 3) had follow-up of one year or more. Both weight loss and weight maintenance trials were included. Abstracts, pseudo-randomised trials, head-to-head trials and open-label studies were excluded.
Data collection and analysis
Two reviewers independently assessed all potentially relevant reports for inclusion and methodological quality. Data were extracted using double data entry. The primary outcome measure was weight loss.
Sixteen orlistat (n = 10,631), 10 sibutramine (n = 2623) and four rimonabant trials (n = 6365) met inclusion criteria. Attrition rates averaged 30% to 40%. Compared to placebo, orlistat reduced weight by 2.9 kg (95% confidence interval (CI) 2.5 to 3.2 kg), sibutramine by 4.2 kg (95% CI 3.6 to 4.7 kg), and rimonabant by 4.7 kg (95% CI 4.1 to 5.3 kg). Patients on active drug therapy were significantly more likely to achieve 5% and 10% weight loss thresholds. Placebo-controlled weight losses were consistently lower in patients with diabetes. Orlistat reduced diabetes incidence, improved total cholesterol, LDL-cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered HDL levels. Sibutramine improved HDL and triglyceride levels but raised blood pressure and pulse rate. Rimonabant improved HDL-cholesterol, triglyceride and blood pressure levels and glycaemic control in patients with diabetes but increased the risk of mood disorders.
Orlistat, sibutramine and rimonabant have been studied in trials of one year or longer. Internal validity of studies was limited by high attrition rates. All three antiobesity agents are modestly effective in reducing weight and have differing effects on cardiovascular risk and adverse effects profiles. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required.
Plain language summary
Long-term drug pharmacotherapy for obesity and overweight
This review assessed the long-term benefits and risks of approved anti-obesity drugs in clinical trials of 1 to 4 years duration. Sixteen orlistat (10,631 patients), 10 sibutramine (2623 patients) and four rimonabant (6635 patients) studies were examined. High drop-out rates (30% to 40%) were a limitation of nearly all studies. Compared to placebo, all three drugs reduced weight by around five kg or less and orlistat reduced the number of high-risk patients who developed diabetes. No data to show that any of the three drugs lowers the risk of death or cardiovascular disease were found. The most prominent side effects were gastrointestinal for orlistat, cardiovascular for sibutramine (raised blood pressure and/or pulse rate) and psychiatric for rimonabant (mood disorders). In Europe, rimonabant is contraindicated for patients with severe depression and/or patients who are treated with antidepressive medications. Rimonabant is furthermore not recommended for patients with other untreated psychiatric conditions.
We conclude that: 1. average weight losses with current anti-obesity agents appear modest but may be of clinical benefit, and 2. better studies designed to examine mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.
從MEDLINE、EMBASE、the Cochrane Controlled Trials Register (CENTRAL)、the Current Science Metaregister of Controlled Trials和原始研究與評論文章(reviews)所列舉的參考文獻清單，去尋找相關的研究。最後一次進行檢索的日期是2002年12月，並且聯繫藥品製造商和兩個肥胖專家，以瞭解是否有未發表的試驗。搜索時並沒有語言的限制。
已核准的抗肥胖藥物進行減重和維持體重的雙盲、隨機對照試驗，同時必須合乎下列條件: (1)納入過重或肥胖的成年人。(2)包括一個安慰劑對照組或是比較兩種或更多種抗肥胖藥物。(3)使用治療意向分析法(intentiontotreat analysis)。(4)起碼追蹤一年以上。文摘和偽隨機試驗不納入選擇範圍內。
在八個抗肥胖藥物的調查中，只有羅氏鮮(orlistat)和諾美婷(sibutramine)的試驗合乎納入標準。總共選取11個羅氏鮮體重減輕的研究(其中4個研究有第二年體重維持階段的報告)和5個諾美婷的研究(3個體重減輕和2個體重維持的試驗)。在羅氏鮮體重減輕的研究流失率平均為33 %，諾美婷的研究為43%，所有患者都接受改變生活型態的介入措施。相較於安慰劑，羅氏鮮治療的患者體重減輕2.7公斤(95% CI：2.3公斤至3.1公斤)或2.9%(95% CI：2.3至3.4)，至於諾美婷治療的患者體重減輕更達到4.3公斤(95%CI：3.6至4.9)或4.6%(95%CI：3.8至5.4)。體重減輕10%以上的病人數目在羅氏鮮為12% (95% CI: 8至16)，諾美婷更達到15% (95% CI: 4至27)。減重維持的試驗結果類似。羅氏鮮會造成胃腸道的副作用，諾美婷則是血壓和脈搏些微增加。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。