An Indirect Comparison of Basal Insulin Plus Once-Weekly Semaglutide and Fully Optimised Basal–Bolus Insulin in Type 2 Diabetes

Introduction: To date, there have been few head-to-head comparisons between semaglutide once-weekly (OW) and short-acting meal-time insulin in participants with type 2 diabetes (T2D) treated with basal insulin and requiring treatment intensification. This indirect comparison evaluated the effects of these regimens on glycated haemoglobin (HbA_1c), body weight, hypoglycaemia, and other clinically relevant outcomes. Methods: A post-hoc, unanchored, individual participant data meta-analysis was conducted on the basis of data from single treatment arms in the SUSTAIN 5 and DUAL 7 trials. Semaglutide 0.5 mg OW and 1.0 mg OW plus basal insulin were compared with an optimised (treat-to-target) basal–bolus regimen of insulin glargine and insulin aspart over 26 weeks, using regression adjustment to account for baseline differences between the trials. Results: Over 26 weeks, semaglutide 1.0 mg OW plus basal insulin reduced mean HbA_1c by significantly more than the basal–bolus regimen (treatment difference: − 0.36%; p = 0.003), while semaglutide 0.5 mg OW plus basal insulin was comparable with basal–bolus insulin (treatment difference: 0.08%, p = 0.53). Both doses of semaglutide were associated with significant weight loss relative to insulin intensification (treatment differences: 6.8–9.4 kg; p < 0.001). At both doses, semaglutide intensification required less basal insulin per day than bolus intensification, and more participants on semaglutide met HbA_1c targets of < 7.0% and ≤ 6.5% without hypoglycaemia or weight gain (odds ratio [OR] for < 7.0%, 21.9; OR for ≤ 6.5%, 16.2; both p < 0.001). Conclusions: In T2D uncontrolled by basal insulin, intensification with semaglutide 1.0 mg OW was associated with better glycaemic control, weight loss, and reduced hypoglycaemia versus a basal–bolus regimen, while limiting the treatment burden associated with frequent injections. Clinicians could consider treatment intensification with semaglutide when T2D is uncontrolled by basal insulin, especially when weight management is a priority. Effective glycaemic control coupled with weight management can alleviate the burden of diabetes-associated complications.