Cardiovascular safety of long-term anti-obesity drugs in subjects with overweight or obesity: a systematic review and meta-analysis

Purpose Anti-obesity therapy can reduce body weight; however, it is not clear whether it can reduce major adverse cardiovascular events (MACEs). We conducted a systematic review and meta-analysis to assess the effect of long-term anti-obesity drugs on MACEs in individuals with overweight or obesity. Methods The MEDLINE, Embase, and Cochrane Library databases and clinical trial registries (https://clinicaltrials.gov) were searched up to 3 May 2021 for randomized controlled trials (RCT) that compared anti-obesity drugs with controls and reported cardiovascular events in subjects with overweight or obesity. Heterogeneity was described by the I-2 value. The Mantel-Haenszel randomized effects model was adopted to calculate risk ratios (RR) and weighted mean differences (WMD). Sensitivity analysis was used to assess the stability of the effects. Publication bias was assessed by Begg's funnel plot and Egger's test. The Cochrane Collaboration risk-of-bias tool was used to evaluate the bias of each included RCT. Results Twelve articles were included; 21,391 and 17,618 subjects were in the anti-obesity drug and placebo groups, respectively. There was no difference in MACEs between the anti-obesity drug and placebo groups (RR 0.99; 95% CI: 0.88-1.12). Compared with placebo, anti-obesity interventions reduced body weight (WMD: -3.96 kg; 95% CI: -4.89, -3.03) and improved lipid and blood glucose profiles. The intervention also did not increase the incidence of depression or anxiety or the risk of suicidal ideation. Conclusion Long-term anti-obesity drugs did not show a benefit in lowering MACEs in overweight or obese subjects, although the drugs resulted in a decrease in body weight and improved cardiometabolic parameters.