AbstractObjectiveTo examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight problems or obesity by meta-analysis and systematic review.MethodsMedical Subject Headings (MeSH) and free-text terms related to phentermine/topiramate were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE up to April 18, 2020. The quality of randomized controlled trials was evaluated by Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models. Our systematic review protocol, registered on PROSPERO (registration number CRD42020188324).ResultsPhentermine/topiramate therapy resulted in a weight loss of 7.73 kg (95% confidence interval [CI]: 6.60, 8.85) compared to placebo. For phentermine/topiramate subjects in different weight loss subgroups, the weight loss of subjects with ≥5%, ≥10%, and ≥15% baseline weight loss were 3.18 (95% CI: 2.75, 3.67), 5.32 (95% CI: 4.53, 6.25), and 5.65 (95% CI: 3.55, 9.01), respectively. Phentermine/topiramate reduced waist circumference, blood pressure, blood sugar levels, and lipid levels. The adverse effects associated with the treatment mainly included Dysgeusia, Paresthesia, Dry mouth.ConclusionsPhentermine/topiramate reduced body weight and was well tolerated. However, it increased the risk of nervous system-related adverse events to a certain extent, but the symptoms are not serious. Long-term clinical and pharmacological studies are needed to understand the long-term efficacy and safety of phentermine/topiramate.Study Importance QuestionsPhentermine/topiramate was approved by the FDA as an anti-obesity drug. However, the European Medicines Agency refused marketing authorization for phentermine/topiramate owing to safety concerns.Phentermine/topiramate reduced body weight and was well tolerated. However, it remarkably increased the risk of nervous system-related adverse events.In this study, the efficacy and incidence of adverse events of phentermine/topiramate were further evaluated through meta-analysis to provide reference for the clinical use of phentermine/topiramate.