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.