Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review

Abstract

Weight management after metabolic and bariatric surgery remains a persistent clinical challenge, particularly when patients experience insufficient weight loss or progressive weight regain following the postoperative nadir. In recent years, pharmacological therapies targeting gut-derived hormones have reshaped the therapeutic approach, offering nonsurgical strategies that directly influence appetite regulation, satiety, and energy balance. Single agonists acting on the glucagon-like peptide one receptor have demonstrated meaningful reductions in body weight among postoperative patients, while dual agonists that target both the glucagon-like peptide one receptor and the glucose-dependent insulinotropic polypeptide receptor have shown even greater weight reduction in early studies, suggesting enhanced therapeutic potential. These benefits, however, must be interpreted within the unique anatomical, nutritional, and behavioral context of individuals who have undergone metabolic and bariatric procedures, as they are inherently at higher risk for micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns. Successful treatment requires a balanced integration of pharmacotherapy, individualized nutritional guidance, psychological support, and a patient-centered model of long-term care. Although emerging evidence is promising, dedicated clinical trials are still needed to directly compare the efficacy, safety, and sustainability of single versus dual agonist therapies in postoperative populations. Furthermore, culturally sensitive dietary strategies and shared decision-making processes are essential to enhance adherence, optimize long-term outcomes, and ensure equitable access to treatment. Ultimately, these therapies represent a significant advance in addressing postoperative weight challenges, but their full potential will rely on comprehensive, multidisciplinary frameworks that support both biological and behavioral aspects of chronic weight management.

Keywords: bariatric surgery; glucagon-like peptide 1; glucose-dependent insulinotropic polypeptide; pharmacotherapy; weight gain; weight loss.

Figure 1

Illustrative Conceptual Model of Weight-regain Patterns After MBS. The figure summarizes common long-term weight trajectories after MBS and the multifactorial contributors to insufficient weight loss (IWL) and weight regain (WR). The top panel depicts two suboptimal outcome patterns: IWL, defined as failure to achieve ≥50% excess weight loss within 1–2 years, and WR, characterized by progressive weight increase after reaching nadir weight. These patterns reflect the interaction of physiological, behavioral, psychological, and nutritional factors. The graph presents illustrative long-term trajectories of weight change after surgery, showing that while most patients achieve substantial and durable reductions, a subset experience IWL, represented by a flattened weight-loss curve, or WR, characterized by progressive regain after nadir. Reported prevalence varies by procedure and duration of follow-up, with WR affecting up to 40% of patients at 5 years after sleeve gastrectomy and even higher rates documented following laparoscopic adjustable gastric banding in long-term cohorts [7,17,18,19,24,39]. This figure is intended to provide conceptual context for post-MBS weight recidivism and does not depict the pharmacologic mechanisms of incretin-based therapies, which are addressed separately in the text and tables.