Clinical Outcomes of Tirzepatide After Metabolic Bariatric Surgery: A Systematic Review.

Background and Objectives: Suboptimal weight outcomes, including recurrent weight gain (RWG) and insufficient weight loss (IWL), remain important clinical challenges after metabolic bariatric surgery (MBS). Although tirzepatide has demonstrated substantial weight loss in nonsurgical populations, its role after MBS remains uncertain. This systematic review evaluated the clinical outcomes of tirzepatide initiated after MBS in adults. Methods: We conducted a systematic review following PRISMA 2020 guidance. PubMed (MEDLINE), Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception through June 2026. Eligible studies included adults with prior MBS who received tirzepatide and reported weight, metabolic, or safety outcomes. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results: Five observational studies met the inclusion criteria. Across studies, tirzepatide was associated with clinically meaningful weight loss after MBS. Mean percent total body weight loss (%TBWL) ranged from 12.0% to 18.1% at the last available follow-up (6-12 months), and a high proportion of patients achieved ≥5%, ≥10%, and ≥15% TBWL where reported. Absolute reductions in body weight and body mass index were observed in studies reporting these outcomes. One study reported reductions in both fat mass and fat-free mass following tirzepatide treatment. Limited data suggested modest changes in glycemic and lipid parameters. Available safety data suggested that tirzepatide appeared to be generally well tolerated, although safety data were limited and follow-up was short. Mild gastrointestinal adverse events were the most reported, and no serious treatment-related adverse events were reported. Risk of bias was rated as low in two studies and moderate in three, and the certainty of evidence for comparative weight-loss outcomes was rated as very low. Conclusions: Current observational evidence suggests that tirzepatide may provide clinically meaningful additional weight loss after MBS; however, the available evidence remains limited and heterogeneous. Larger prospective comparative studies with longer follow-up are needed to confirm its efficacy, durability, safety, and comparative effectiveness in this population.