Journal: BMC medicine 2025;23(1):398
PMID: 40691794
Obesity is a major global health concern, and anti-obesity medications (AOMs) are commonly prescribed to help people lose weight. However, less is known about what happens to body weight after these medications are stopped. This systematic review and meta-analysis examined how body weight changes after discontinuing AOMs. Researchers analysed randomised controlled trials in which participants had taken AOM for at least four weeks and were followed for at least four weeks after stopping treatment.
Results showed that at four weeks after discontinuation, some weight loss was still maintained compared to people who had not received medication. However, this effect was small and not statistically significant overall. By eight weeks after stopping treatment, significant weight regain was observed, and this regain continued up to 20 weeks. The pattern and degree of weight regain varied depending on the type of medication and study design.
It was concluded that the benefits of AOM may diminish after discontinuation, and weight regain is likely without continued treatment or additional lifestyle support. Healthcare professionals should consider long-term weight management strategies, behavioural support, and patient education when prescribing AOMs, especially if treatment discontinuation is anticipated.
None
AOMs produce clinically meaningful weight loss during active treatment, but partial weight regain may occur after discontinuation.
Weight regain following cessation of therapy reflects weight cycling and may be influenced by metabolic adaptation, including reductions in resting energy expenditure after weight loss.
Regular physical activity may help shift energy balance toward expenditure rather than storage, potentially attenuating post-treatment weight regain.
Introduction
This study aimed to evaluate the long-term effects of anti-obesity medications (AOMs) on body weight trajectories following treatment discontinuation, with a focus on patterns of weight change over time.
Methods
This was a systematic review and meta-analysis of eleven randomised controlled trials evaluating anti-obesity medications. Eight trials used placebo comparators and three used active drug controls, comprising 1,573 participants in intervention groups and 893 in control groups. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
Compared with controls, AOM discontinuation was associated with greater weight regain overall, with the magnitude varying by follow-up time.
At week 4, AOMs were still associated with a non-significant 0.32kg weight loss (95% CI −3.60 to 2.97; P = 0.85; I² = 83%), whereas significant weight regain was observed at week 8 (WMD = 1.50kg; 95% CI 1.32–1.68; P < 0.0001; I² = 0%), week 12 (1.76kg; 95% CI 1.29–2.24; P < 0.0001; I² = 72%), week 20 (2.50kg; 95% CI 2.27–2.73; P < 0.0001; I² = 0%), week 26 (2.30kg; 95% CI 0.53–4.07; P = 0.01; I² = 0%), and week 52 (2.47kg; 95% CI 0.24–4.70; P = 0.03; I² = 92%).
increased through weeks 12–20, then stabilised. Body weight at 52 weeks remained lower than baseline.
Significant weight regain was observed in both placebo-controlled (WMD = 1.72kg; 95% CI 1.20–2.23; P < 0.001; I² = 83%) and active-controlled studies (WMD = 2.37kg; 95% CI 0.30–4.44; P = 0.02; I² = 0%), with no between-subgroup difference (P = 0.55).
GLP-1–based agents showed significant weight regain versus controls (WMD = 1.78kg; 95% CI 0.76–2.80; P = 0.006; I² = 85%), whereas non–GLP-1 strategies did not (P = 0.18).
Conclusion
Significant weight regain occurred 8 weeks after discontinuation of AOMs and was sustained through 20 weeks. Weight regain patterns varied across drug classes and study designs.
Long-term or sustained weight management strategies should be considered when prescribing AOMs, as weight regain after discontinuation is common. The results from this study suggest that support is particularly important in the first 6 months following discontinuation of AOMs, when weight regain tends to taper off.
Ongoing lifestyle interventions, particularly structured exercise, should accompany pharmacotherapy to help minimise weight regain.
Individualised nutritional follow-ups and monitoring may support early identification and management of post-treatment weight changes.
Longer-term follow-up studies are needed to better characterise weight trajectories and determinants of weight change after AOM discontinuation.
Future analyses should incorporate additional efficacy outcomes beyond weight and body mass index, such as body composition and metabolic markers.
Larger numbers of trials with more standardised intervention protocols would help reduce heterogeneity and strengthen evidence.
Further investigation is required to clarify the impact of adverse events and treatment discontinuation on post-treatment weight regain.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
© 2025. The Author(s).
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