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

Abstract

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.

Keywords: BMI; Heart Disease; Pharmacotherapy; Vascular.

Figure 1

Study selection flowsheet

Figure 2

Network of included studies (across outcomes). Outcomes reported in each study are included in Table 1.

Figure 3

Pooled effect of any pharmacologic therapy for obesity compared to placebo on each study outcome reported as standardized mean differences.

Figure 4

Impact of individual agents against placebo after 1 year of treatment on (A) measures of blood glucose control - fasting blood glucose and hemoglobin A1c; (B) measures of cholesterol metabolism – low density lipoproteins (LDL) and high density lipoproteins (HDL); (C) blood pressure; and (D) waist circumference.