Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A Systematic Review and Network Meta-analysis

Published:January 03, 2018DOI:

      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.


      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).


      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.


      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.


      Abbreviations used in this paper:

      BMI (body mass index), BP (blood pressure), CI (confidence interval), FBG (fasting blood glucose), FDA (Food and Drug Administration), HDL (high-density lipoprotein), IQR (interquartile range), LDL (low-density lipoprotein), RCT (randomized controlled trial), SMD (standardized mean difference), WC (waist circumference), WMD (weighted mean difference)
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