Insulin Efsitora Demonstrates Similar Efficacy and Safety Profiles to Insulin Icodec in Insulin‐Experienced Individuals With Type 2 Diabetes Mellitus: Matching‐Adjusted Indirect Comparisons of QWINT ‐3 Versus ONWARDS 2, and QWINT ‐4 Versus ONWARDS 4

Aims To conduct indirect treatment comparisons (ITCs) of insulin efsitora alfa (efsitora) versus insulin icodec (icodec) in insulin‐experienced individuals with Type 2 Diabetes Mellitus. Methods Efficacy, safety and patient reported outcomes were compared via matching‐adjusted ITCs using results from randomised controlled trials: QWINT‐3 versus ONWARDS 2 (basal‐insulin experienced individuals) and QWINT‐4 versus ONWARDS 4 (basal‐bolus insulin‐experienced individuals). Results In basal insulin‐experienced participants, efsitora was comparable to icodec for change from baseline (CfB) in HbA1c (%) (efficacy estimand mean difference [MD] [95% CI]: 0.137 [−0.058, 0.333]), proportion of participants (PoP) discontinuing treatment due to adverse event (risk difference: −0.0002 [−0.0223, 0.0220]) and CfB in Diabetes Treatment Satisfaction Questionnaire‐Change (DTSQc) (MD: 1.01 [−0.243, 2.27]). Efsitora exhibited significantly reduced weight gain (MD: −1.52 kg [−2.60, −0.447]) and had lower event rates of Level 2 or 3 hypoglycaemia (rate ratio: 0.436 [0.241, 0.786]) versus icodec, despite no significant difference in PoP with Level 2 or 3 hypoglycaemia (odds ratio [OR]: 0.581 [0.294, 1.14]). In basal‐bolus insulin‐experienced participants, efsitora was comparable to icodec: CfB in HbA1c (%) (MD: −0.0447 [−0.252, 0.163]); CfB in body weight (kg) (MD: −0.316 [−1.45, 0.817]); PoP with Level 2 or 3 hypoglycaemia (OR: 1.10 [0.698, 1.73]); event rate of Level 2 or 3 hypoglycaemia (rate ratio [95% CI]: 1.03 [0.759, 1.39]). Conclusions These indirect comparisons suggest that efsitora had lower event rates of hypoglycaemia and less weight gain compared to icodec in basal insulin‐experienced participants. Efsitora was comparable to icodec for all other endpoints.