Background & Aims

We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults.

Methods

We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration−approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results

In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m²), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, –4.4 to –3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, –3.5 to –3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors.

Conclusions

In a systematic review and network meta-analysis, we found Food and Drug Administration−approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications. PROSPERO: CRD42016039486.

中文翻译：

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减肥药物对心脏代谢风险的影响：系统评价和网络Meta分析

背景与目标

我们进行了系统的综述和网络荟萃分析，以评估由美国食品药物管理局批准的长期使用的减肥药物对肥胖成年人的心脏代谢风险的总体影响和比较作用。

方法

我们在2017年2月28日之前进行了系统的文献综述，以确定食品和药物管理局批准的减肥药（即奥利司他，洛斯卡林，纳曲酮-安非他酮，芬特明-托吡酯和利拉鲁肽）的效果的随机临床试验与安慰剂或其他活性剂相比，肥胖成人1年或更长时间。感兴趣的结果包括血糖（空腹血糖[FBG]和血红蛋白A1c），胆固醇概况（低密度脂蛋白和高密度脂蛋白），血压（BP；收缩压/舒张压）和腰围（WC）的变化。我们进行了成对和网络荟萃分析，结果以加权和标准化均值差异的形式报告。证据的质量使用GRADE（建议评估，发展和评估等级）进行评级。

结果

在对28项随机对照试验（29,018名参与者；体重指数中位数为36.1 kg / m ^2）的荟萃分析中），我们将减肥药物与FBG（加权平均差异4.0 mg / dL； 95％置信区间介于–4.4至–3.6 mg / dL）和WC（加权平均差异减少3.3 cm；以及95％的置信区间，–3.5至–3.1 cm），相对于安慰剂，收缩压/舒张压BP或胆固醇谱无临床意义的变化（标准均值<0.2）；药物之间的作用不同。使用芬特明-托吡酯与WC的大量减少和FBG，血红蛋白A1c和BP的适度下降有关，并且对胆固醇的影响最小。利拉鲁肽的使用与FBG，血红蛋白A1c和WC的大量减少有关，并且对BP和胆固醇的影响最小。纳曲酮安非他酮的使用与高密度脂蛋白胆固醇的适度增加有关，但对FBG和WC的影响很小。使用奥利司他与降低低密度脂蛋白和高密度脂蛋白胆固醇有关。没有药物能改善所有心脏代谢危险因素。

结论

在系统的审查和网络荟萃分析中，我们发现食品和药物管理局批准的减肥药物对心脏代谢风险的影响仅有中等程度的积极影响。需要进一步的研究来评估这些药物的长期心脏代谢益处。PROSPERO：CRD42016039486。