An Adjusted Indirect Comparison of Once-Weekly Insulin Efsitora Alfa vs. Insulin Icodec for Adults With Type 2 Diabetes Mellitus Previously Treated With Basal-Bolus Insulin
Author(s)
Marvin Heyne, MSc1, Josefine Redig, MSc1, Harpreet Bajaj, MD2, Wenxiu Dong, MSc3, Pratiksha Dutta, MSc1, Alex Pashley, MChem4, Christopher J. Michaels, PhD4, Rachel Tao, MPH4, Michael B. Davidson, DO1.
1Eli Lilly and Company, Indianapolis, IN, USA, 2Endocrine and Metabolic Research, LMC Diabetes and Endocrinology, Brampton, ON, Canada, 3Techdata Service Company, King of Prussia, PA, USA, 4Costello Medical, Cambridge, United Kingdom.
1Eli Lilly and Company, Indianapolis, IN, USA, 2Endocrine and Metabolic Research, LMC Diabetes and Endocrinology, Brampton, ON, Canada, 3Techdata Service Company, King of Prussia, PA, USA, 4Costello Medical, Cambridge, United Kingdom.
OBJECTIVES: QWINT-4, a Phase 3 randomised controlled trial (RCT), investigated the efficacy and safety of treating type 2 diabetes mellitus (T2DM) with once-weekly insulin efsitora alfa (efsitora) in adults previously treated with basal-bolus insulin. In the absence of head-to-head evidence, indirect treatment comparisons of efsitora against weekly insulin icodec (icodec) adjusted for baseline HbA1c (%) were conducted.
METHODS: A systematic literature review conducted in May 2024 identified data from a Phase 3 RCT (icodec: ONWARDS 4) for comparison with efsitora (QWINT-4, data on file). The exclusion criteria for ONWARDS 4 were applied to the analysis population for QWINT-4; study design, treatment effect modifiers and outcome definitions were assessed for consistency. While ONWARDS 4 used bolus insulin aspart, QWINT-4 used insulin lispro; these were used at similar mean doses and considered clinically comparable. Analyses were conducted using treatment regimen estimands for efficacy, safety and composite endpoints at Week 26, including those related to glycated haemoglobin (HbA1c), glucose control target achievement, body weight, discontinuations, adverse events, and hypoglycaemia. Matching-adjusted indirect comparisons adjusted for baseline HbA1c (%) were conducted. No adjustment could be applied for the differences in daily and weekly basal, as well as bolus insulin titration schemes between QWINT-4 and ONWARDS 4.
RESULTS: Efsitora was comparable to icodec for key efficacy outcomes, including change from baseline (CfB) in HbA1c (%) (mean difference [95%CI]: -0.04 [-0.25, 0.16]); all safety endpoints, including proportion of patients (PoP) with Level 2/3 hypoglycaemia (odds ratio [OR] [95%CI]: 1.10 [0.70, 1.73]) and CfB in body weight (kg) (mean difference [95%CI]: -0.32 [-1.45, 0.82]). PoP with HbA1c<7 without Level 2/3 hypoglycaemia in prior 12 weeks (OR [95%CI]: 0.94 [0.57, 1.57]) was similarly comparable.
CONCLUSIONS: Efsitora showed comparable results to icodec for key efficacy and safety endpoints in adults with T2DM previously treated with basal-bolus insulin.
METHODS: A systematic literature review conducted in May 2024 identified data from a Phase 3 RCT (icodec: ONWARDS 4) for comparison with efsitora (QWINT-4, data on file). The exclusion criteria for ONWARDS 4 were applied to the analysis population for QWINT-4; study design, treatment effect modifiers and outcome definitions were assessed for consistency. While ONWARDS 4 used bolus insulin aspart, QWINT-4 used insulin lispro; these were used at similar mean doses and considered clinically comparable. Analyses were conducted using treatment regimen estimands for efficacy, safety and composite endpoints at Week 26, including those related to glycated haemoglobin (HbA1c), glucose control target achievement, body weight, discontinuations, adverse events, and hypoglycaemia. Matching-adjusted indirect comparisons adjusted for baseline HbA1c (%) were conducted. No adjustment could be applied for the differences in daily and weekly basal, as well as bolus insulin titration schemes between QWINT-4 and ONWARDS 4.
RESULTS: Efsitora was comparable to icodec for key efficacy outcomes, including change from baseline (CfB) in HbA1c (%) (mean difference [95%CI]: -0.04 [-0.25, 0.16]); all safety endpoints, including proportion of patients (PoP) with Level 2/3 hypoglycaemia (odds ratio [OR] [95%CI]: 1.10 [0.70, 1.73]) and CfB in body weight (kg) (mean difference [95%CI]: -0.32 [-1.45, 0.82]). PoP with HbA1c<7 without Level 2/3 hypoglycaemia in prior 12 weeks (OR [95%CI]: 0.94 [0.57, 1.57]) was similarly comparable.
CONCLUSIONS: Efsitora showed comparable results to icodec for key efficacy and safety endpoints in adults with T2DM previously treated with basal-bolus insulin.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO9
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)