Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies

Abstract

Objectives: The primary objective of this review is to analyze the effects on body weight of discontinuing therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or tirzepatide in patients treated for obesity. In recent months, there has been a considerable increase in the utilization of GLP-1 RAs and GIP/GLP-1 RAs. However, the paucity of available data regarding their medium- to long-term safety remains a salient concern. Of particular significance is the observation of the weight curve following their suspension, a subject that has received scant attention to date. Methods: For this, a bibliographic search was carried out in three electronic databases: PubMed, Cochrane Library and Google Scholar. The following filters were applied: in the last 10 years, Randomized Controlled Trial, Adult: 19+ years. The review was restricted to randomized controlled trials to reduce bias and ensure the high quality of the studies examined. A total of 427 references were identified, 178 articles were read in full, and 13 articles were included in the analysis. Results and Conclusions: The analysis showed a rapid regain of weight after cessation of therapy, regardless of the duration of the treatment with GLP-1 RA or GIP/GLP-1 RA. This rebound is likely to substantially mitigate the metabolic benefits attained through weight loss. Given the efficacy of these drugs, it is essential for future research to focus on elucidating the optimal duration of these treatments or identifying techniques or schemes that involve a reduction in dosages to prevent weight regain.

Keywords: GIP/GLP-1 RA; bariatric surgery; glucacon like peptide (GLP1 RA); liraglutide; semaglutide; tirzepatide; weight regain.

Figure 1

Flow diagram illustrating the process of our review.