Khera R, Pandey A, Chandar AK, et al. Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A Systematic Review and Network Meta-analysis. Gastroenterology. 2018 Apr;154(5):1309-1319.e7. doi: 10.1053/j.gastro.2017.12.024. Epub 2018 Jan 3.
Area Score
Internal Medicine
Public Health
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)

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.

Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

This well done meta analysis of 5 weight loss drugs showed that they lead to modest but significant weight loss and waist circumference but minimal improvement in metabolic vascular risk factors. One would hope that these drugs would be directly evaluated for cardiovascular outcomes soon.

General Internal Medicine-Primary Care(US) rater

Weight lowering agents, what's the bang for your buck? This well designed analysis demonstrates that the metabolic effects of various weight loss agents differ, to a large extent in concordance with their chemistry and biology. Additionally, the overall effect of all is modest weight reduction and little improvement of cardiometabolic risk factors. In context, these agents are intended for relatively short term use, as a component of an overall weight reduction and risk factor modification program. Overall, we know that weight reduction agents have had disappointing results. This analysis sheds some light on the differences in changes in cardiometabolic parameters, depending on the agent chosen, which might impact the selection of an agent, depending on the individual patient's profile.

Public Health rater

I think finding articles which compare surgical methods vs Drugs in the treatment of obesity can be useful for practitioners.

Public Health rater

This systematic review and meta-analysis summarized the effects of weight-loss medication on cardiometabolic risk profiles. As a cardiologist, the information provided by this article is very useful and important esp for giving advice to my patients and colleagues!