An Adjusted Indirect Comparison of Once-Weekly Insulin Efsitora Alfa vs. Insulin Icodec for Adults With Type 2 Diabetes Mellitus Previously Treated With Basal Insulin
Author(s)
Josefine Redig, MSc1, Marvin Heyne, MSc1, Wenxiu Dong, MSc2, Michael B. Davidson, DO1, Pratiksha Dutta, MSc1, Alex Pashley, MChem3, Christopher J. Michaels, PhD3, Rachel Tao, MPH3, Harpreet Bajaj, MD4.
1Eli Lilly and Company, Indianapolis, IN, USA, 2Techdata Service Company, King of Prussia, PA, USA, 3Costello Medical, Cambridge, United Kingdom, 4Endocrine and Metabolic Research, LMC Diabetes and Endocrinology, Brampton, ON, Canada.
1Eli Lilly and Company, Indianapolis, IN, USA, 2Techdata Service Company, King of Prussia, PA, USA, 3Costello Medical, Cambridge, United Kingdom, 4Endocrine and Metabolic Research, LMC Diabetes and Endocrinology, Brampton, ON, Canada.
OBJECTIVES: QWINT-3 was a Phase 3 randomised control trial (RCT), which evaluated the efficacy and safety of once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes mellitus (T2DM) previously treated with basal insulin, without bolus insulin. In the absence of head-to-head evidence, indirect treatment comparisons of efsitora versus weekly insulin icodec (icodec) were conducted.
METHODS: Data from a Phase 3 RCT (icodec: ONWARDS 2) were identified through a systematic literature review conducted in May 2024, for comparison with efsitora (QWINT-3, data on file). Study design, treatment effect modifiers (TEMs), and outcome definitions were evaluated for consistency. ONWARDS 2 exclusion criteria were applied to the QWINT-3 analysis population. Efficacy, safety, patient reported outcomes (PRO) and composite endpoints, including those related to glycated haemoglobin (HbA1c), glucose control target achievement, body weight, discontinuations, adverse events and hypoglycaemia, were assessed at Week 26; outcomes are reported using treatment regimen estimand unless otherwise specified. Matching-adjusted indirect comparisons adjusted for baseline HbA1c (%) were conducted. No adjustment could be applied for the differences in daily and weekly basal insulin titration schemes between QWINT-3 and ONWARDS 2.
RESULTS: Efsitora was comparable to icodec for all efficacy outcomes, including change from baseline (CfB) in HbA1c (%) (efficacy estimand mean difference [MD] [95%CI]: 0.14 [-0.06, 0.33]). Outcomes were comparable or similar for key safety endpoints including proportion of patients (PoP) with Level 2/3 hypoglycaemia (odds ratio [OR] [95%CI] 0.58 [0.29, 1.14]); CfB in body weight (kg) (MD [95%CI] -1.52 [-2.60, -0.45]), PRO (CfB in Diabetes Treatment Satisfaction Questionnaire MD [95%CI]: 1.01 [-0.24, 2.27]). Composite endpoints, including PoP with HbA1c≤6.5 without Level 2/3 hypoglycaemia in prior 12 weeks, were comparable (OR [95%CI]: 0.88 [0.45, 1.73]).
CONCLUSIONS: Efsitora showed comparable results to icodec for all efficacy, composite and key safety endpoints in individuals with T2DM previously treated with basal insulin.
METHODS: Data from a Phase 3 RCT (icodec: ONWARDS 2) were identified through a systematic literature review conducted in May 2024, for comparison with efsitora (QWINT-3, data on file). Study design, treatment effect modifiers (TEMs), and outcome definitions were evaluated for consistency. ONWARDS 2 exclusion criteria were applied to the QWINT-3 analysis population. Efficacy, safety, patient reported outcomes (PRO) and composite endpoints, including those related to glycated haemoglobin (HbA1c), glucose control target achievement, body weight, discontinuations, adverse events and hypoglycaemia, were assessed at Week 26; outcomes are reported using treatment regimen estimand unless otherwise specified. Matching-adjusted indirect comparisons adjusted for baseline HbA1c (%) were conducted. No adjustment could be applied for the differences in daily and weekly basal insulin titration schemes between QWINT-3 and ONWARDS 2.
RESULTS: Efsitora was comparable to icodec for all efficacy outcomes, including change from baseline (CfB) in HbA1c (%) (efficacy estimand mean difference [MD] [95%CI]: 0.14 [-0.06, 0.33]). Outcomes were comparable or similar for key safety endpoints including proportion of patients (PoP) with Level 2/3 hypoglycaemia (odds ratio [OR] [95%CI] 0.58 [0.29, 1.14]); CfB in body weight (kg) (MD [95%CI] -1.52 [-2.60, -0.45]), PRO (CfB in Diabetes Treatment Satisfaction Questionnaire MD [95%CI]: 1.01 [-0.24, 2.27]). Composite endpoints, including PoP with HbA1c≤6.5 without Level 2/3 hypoglycaemia in prior 12 weeks, were comparable (OR [95%CI]: 0.88 [0.45, 1.73]).
CONCLUSIONS: Efsitora showed comparable results to icodec for all efficacy, composite and key safety endpoints in individuals with T2DM previously treated with basal insulin.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO8
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)