The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery—a Retrospective Analysis

Abstract

Purpose About 20–25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric metabolic surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with the GLP-1 receptor agonist semaglutide in non-diabetic patients with WR or IWL after BS. Materials and Methods Post-bariatric patients without type 2 diabetes (T2D) with WR or IWL (n = 44) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, and liver enzymes. Results Patients started semaglutide 64.7 ± 47.6 months (mean ± SD) after BS. At initiation of semaglutide, WR after post-bariatric weight nadir was 12.3 ± 14.4% (mean ± SD). Total weight loss during semaglutide treatment was − 6.0 ± 4.3% (mean ± SD, p < 0.001) after 3 months (3.2 months, IQR 3.0–3.5, n = 38) and − 10.3 ± 5.5% (mean ± SD, p < 0.001) after 6 months (5.8 months, IQR 5.8–6.4, n = 20). At 3 months, categorical weight loss was > 5% in 61% of patients, > 10% in 16% of patients, and > 15% in 2% of patients. Triglycerides (OR = 0.99; p < 0.05), ALT (OR = 0.87; p = 0.05), and AST (OR = 0.89; p < 0.05) at baseline were negatively associated with weight loss of at least 5% at 3 months’ follow-up (p < 0.05). Conclusion Treatment options to manage post-bariatric excess weight (regain) are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients. However, these results need to be confirmed in a prospective randomized controlled trial to close the gap between lifestyle intervention and revision surgery in patients with IWL or WR after BS. Graphical abstract

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery

“…Furthermore, statistical analysis showed no significant difference in weight-loss outcomes between patients with and without a history of BS. These findings align with prior studies that have examined the efficacy of GLP-1-RAs in managing obesity [11][12][13][14][15][16]; however, our study is distinctive as the first, to our knowledge, to employ the higher dose of semaglutide, which is currently recommended for individuals living with obesity. This outcome implies that post-BS alterations in hormonal secretions or changes in gut microbiota do not significantly influence the response to GLP-1-RAs [21].…”

“…Our study uniquely provides real-world evidence of the effectiveness of semaglutide in patients with a history of BS who have not achieved sufficient weight loss or who have experienced weight regain. Notably, our research is distinctive in its approach of comparing the efficacy of semaglutide patients with and without a history of BS, which is an element not specifically addressed in previous studies [11][12][13][14][15][16]. Moreover, this is the first study of its kind, to our knowledge, to exclusively focus on individuals with severe obesity, defined as having a BMI greater than 40 kg/m 2 and associated comorbidities (hypertension, dyslipidemia, history of CVD, or OSA with equipment).…”

“…has not yet been fully evaluated. Previous studies have investigated the use of liraglutide [11][12][13] or semaglutide [14][15][16] at lower doses after BS, but few have specifically targeted this patient population. These studies show efficacy on weight loss with sometimes superior effects compared with a new BS [11].…”

“…However, the efficacy of semaglutide in patients with a body mass index (BMI) ≥ 40 kg/m 2 who have undergone BS and still have obesity‐related comorbidities has not yet been fully evaluated. Previous studies have investigated the use of liraglutide [11–13] or semaglutide [14–16] at lower doses after BS, but few have specifically targeted this patient population. These studies show efficacy on weight loss with sometimes superior effects compared with a new BS [11].…”

Novel Anti-Obesity Pharmacotherapies

“…These latest bariatric surgery guidelines stem from the clearer understanding of the underpinnings of energy metabolism and scientific progress leading to necessary revision of the original guidelines [23]. While bariatric surgery is able to achieve 30-35% weight loss, novel AOMs can be utilized as adjunctive pharmacotherapy pre-or post-operatively to target weight gain [24]. Thus, combinatory novel AOMs coupled with surgical intervention are likely to garner more evidence in the future.…”