Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications

Globally, obesity has emerged as a significant public health concern, imposing detrimental impacts on human health. The purpose of our study was to explore the long-term effects of anti-obesity medications (AOMs) on body weight and to draw the trajectory of weight change after discontinuation of AOMs. PubMed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies, and Clinicaltrials.gov were searched from the inception to March 2024. Randomized controlled trials of AOMs conducted in population for at least 4 weeks and followed for 4 or more weeks after discontinuation were included. Weight change during treatment and after drug discontinuation was also reported. Random-effect model and meta-regression analysis were accordingly used. At week 4 after discontinuation, compared with the control group, AOM treatment still had weight loss effect (WMD = - 0.32 kg, 95% CI - 3.60-2.97, P = 0.85, I2 = 83%). At 8 weeks after drug discontinuation, AOMs were associated with significant weight regain compared with the control group (WMD = 1.50 kg, 95% CI 1.32-1.68, P < 0.0001, I2 = 0.0%). The weight regain trend remained at 12 and 20 weeks (WMD = 1.76 kg, 95% CI 1.29-2.24, P < 0.0001, I2 = 72.0%; WMD = 2.50 kg, 95% CI 2.27-2.73, P < 0.0001, I2 = 0.0%). Among the different subgroups of AOMs, significant weight regain after 12 weeks of drug discontinuation was observed only in studies with glucagon-like peptide 1 receptor agonist (GLP-1 RA) related drugs. In addition, studies in which weight loss was greater during treatment than in the control group and studies in which lifestyle interventions were continued observed significant weight gain after drug discontinuation. Significant weight regain occurred 8 weeks after discontinuation of AOMs and was sustained through 20 weeks. Different weight regain was observed in subjects with different characteristics. Studies with longer follow-up duration are required to further investigate the potential factors associated with weight change after discontinuation of treatment.