Metabolic consequences of semaglutide discontinuation in type 2 diabetes: a retrospective cohort study

Objective Semaglutide is recognised for its superior effects on glycaemic control and weight management. However, the clinical outcomes following semaglutide discontinuation are not well established. This study aimed to evaluate the clinical and metabolic consequences of such switch. Design This was a retrospective cohort study utilising a non-interventional, single-arm, before-and-after design. Methods This study included 120 patients with type 2 diabetes who discontinued semaglutide and transitioned to alternative regimens. Key metabolic parameters, such as body weight, glycated haemoglobin, fasting and postprandial glucose and lipid profiles, were extracted from medical records at baseline and at 6 months post-switch. Results Across the entire cohort, no significant changes were observed in any metabolic parameter between baseline and the follow-up, suggesting short-term metabolic stability. However, subgroup analyses revealed notable trends: patients switched to dulaglutide and liraglutide tended to exhibit deteriorating glycaemic control and body weight gain. In contrast, the basal insulin group showed relatively stable body weight. Conclusion The trends of weight regain and worsening glycaemic control following transition to less potent glucagon-like peptide-1 receptor agonists are consistent with semaglutide’s superior metabolic efficacy. Nonetheless, the study’s limited statistical power and short duration may obscure subtle but clinically meaningful changes. These findings suggest that long-term alternative regimens may not fully sustain the metabolic benefits achieved with semaglutide.