INTRODUCTION: Insufficient weight loss (IWL) or weight regain (WR) after metabolic bariatric surgery remains a challenge in obesity management. Therefore, this study aimed to retrospectively evaluate the impact of adjunctive tirzepatide therapy over 6 months following sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). METHODS: Post-bariatric patients without type 2 diabetes with IWL or WR (n = 21) were analyzed. Key outcomes included changes in weight, BMI, waist circumference, body composition, basal metabolism, metabolic markers, and inflammatory markers. Subgroup analyses assessed differences based on sex, surgery type, and classification as IWL or WR. Linear regression was performed to identify predictors of weight loss outcomes. RESULTS: At 6 months, mean total weight loss was 12.0 % ± 3.4 % (p <
0.001), with significant reductions in BMI, waist circumference, body fat percentage, and HbA1c. Basal metabolism declined proportionally with weight loss. Weight loss ≥ 5 % occurred in 100.0 % of patients, ≥ 10 % in 76.5 %, and ≥ 15 % in 23.5 %. Basal metabolism differences between RYGB and SG patients converged by 6 months. Male and female patients showed comparable weight loss and metabolic adaptation. IWL patients experienced less fat-free mass loss at 3 months compared to WR (p <
0.05). Baseline BMI nadir, prior weight regain, body composition, and chronic inflammation were significant predictors of weight loss outcomes. DISCUSSION: Tirzepatide treatment significantly enhances weight loss and metabolic health in post-bariatric patients, regardless of surgery type or sex. Differences in fat-free mass loss highlight the need for tailored interventions in IWL and WR groups. Baseline factors, including inflammation and body composition, may help predict treatment success.