Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo. Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events. Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ −3.07 Kg, 95% CI, −3.76 to −2.37), phentermine plus topiramate (N = 2985; ∆ −9.77 Kg; 95% CI, −11.73 to −7.81), lorcaserin (N = 16,856; ∆ −3.08 Kg; 95% CI, –3.49 to –2.66), naltrexone plus bupropion (N = 3239; ∆ −4.39 Kg; 95% CI, −5.05 to −3.72) and liraglutide (N = 4978; ∆ −5.25 Kg; 95% CI, −6.17 to −4.32), compared to placebo (all p < 0.00001).