Bariatric Surgery as a Rescue Strategy After Semaglutide or Tirzepatide

To evaluate 2-year weight loss after bariatric surgery among adults with intolerable adverse effects or inadequate weight loss with semaglutide or tirzepatide.

Semaglutide and tirzepatide are effective obesity medications, but intolerance and inadequate weight loss are common, creating uncertainty about next-step therapy.

This retrospective cohort included adults with BMI ≥35 kg/m² undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at Cleveland Clinic hospitals from 2018 to 2024. Electronic health record and dispensing data classified preoperative semaglutide or tirzepatide exposure and response. The primary outcome was estimated 2-year total body weight loss (TBWL), stratified by procedure and type 2 diabetes (T2DM) status.

Among 4929 patients, 4661 had no prior exposure (comparator group), 61 discontinued semaglutide or tirzepatide because of intolerable adverse effects, and 207 had inadequate weight-loss response. Before surgery, estimated 2-year medication-associated weight change was a 1.4% gain in the intolerance group and 1.5% TBWL in the inadequate-response group. After surgery, 2-year TBWL in the intolerance group was 27.9% and 22.7% after RYGB and 20.1% and 21.6% after SG among patients without and with T2DM, respectively. Corresponding estimates in the inadequate-response group were 35.8%, 27.4%, 14.3%, and 14.2%. For comparison, corresponding 2-year TBWL estimates in the comparator group were 33.3%, 28.7%, 23.6%, and 19.9%. In adjusted analysis of the inadequate-response group, RYGB was associated with greater 2-year TBWL than SG (32.7% vs. 17.8%; difference, 14.9 percentage points [95% CI, 13.1%-16.7%]).

Bariatric surgery was associated with clinically meaningful 2-year weight loss after semaglutide or tirzepatide intolerance or inadequate response, with RYGB potentially offering greater benefit after inadequate response.