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.