Impatto della terapia con farmaci incretino-mimetici sugli outcomes ponderali precoci in una coorte di pazienti sottoposti a chirurgia bariatrica

Background. Obesity represents one of the major global public health challenges and is associated with an increased risk of cardiometabolic complications. In recent years, incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP/GLP-1) receptor agonists, have demonstrated substantial efficacy in promoting weight loss and improving metabolic outcomes. Bariatric surgery remains the most effective treatment for severe obesity; however, postoperative weight loss is characterized by marked interindividual variability. In this context, the use of incretin-based therapies in the preoperative setting may represent a strategy to optimize postoperative outcomes. Objective. To evaluate the association between preoperative incretin-based therapy and early and mid-term postoperative weight loss after bariatric surgery in patients affected by obesity. Methods. This retrospective observational study included 169 patients with obesity who underwent bariatric surgery between January and June 2025 at the Center for the Medical and Surgical Treatment of Obesity, Azienda Ospedale-Università di Padova. Patients were stratified according to exposure to preoperative incretin-based therapy (n = 40) or no anti-obesity pharmacological treatment (n = 129). Primary endpoints were the achievement of ≥ 10% and ≥ 15% Total Weight Loss (TWL%) 1 month after bariatric surgery, and ≥ 25% and ≥ 30% TWL% 6 months after bariatric surgery. TWL% was also analyzed as a continuous outcome at the same postoperative time points. Associations for categorical endpoints were assessed using chi-square tests and odds ratios (OR) with 95% confidence intervals (95% CI), while continuous TWL% was compared using the Wilcoxon rank-sum test. Results. One month after bariatric surgery, patients receiving preoperative incretin-based therapy were significantly more likely to achieve ≥ 10% TWL% (90.0% vs 72.9%; p = 0.025; OR 3.35, 95% CI 1.10-10.20) and ≥ 15% TWL% (62.5% vs 27.9%; p < 0.001; OR 4.31, 95% CI 2.00-9.30) compared with untreated patients. Consistently, TWL% as a continuous outcome was significantly higher in the treated group at 1 month (median [IQR]: 16.06 [6.37] vs 12.73 [6.65]; p < 0.001). Six months after bariatric surgery, achievement of ≥ 25% TWL% was more frequent in patients previously treated with incretin-based therapy (80.0% vs 62.8%; p = 0.043; OR 2.37, 95% CI 1.00-5.60), whereas no significant association was observed for the ≥ 30% TWL% threshold (OR 1.38, 95% CI 0.70-2.80; p = 0.378). At the same time point, continuous TWL% remained numerically higher in the treated group (29.33 [8.25] vs 27.31 [10.99]), although the difference did not reach statistical significance. Conclusions. Preoperative incretin-based therapy was associated with a higher likelihood of achieving clinically meaningful early postoperative weight loss and with greater TWL% 1 month after bariatric surgery. The attenuation of between-group differences 6 months after surgery suggests that the additive effect of preoperative pharmacotherapy may be more pronounced in the early postoperative phase, while longer-term weight loss appears to be predominantly driven by the surgical intervention itself. These findings support the potential role of incretin-based therapy as a bridge-to-surgery strategy; however, confirmation in prospective randomized studies accounting for baseline differences is required.