Journal Article

Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial

Pérez Manghi, Federico C, Li, Xiaoqi, Blevins, Thomas, Carr, Molly C, Murthy, Sreenivasa, Dahl, Dominik, Ortiz Carrasquillo, Ramon, Chang, Annette M, Katz, Michelle

2025

Overview

Insulin efsitora alfa (efsitora), a once-weekly basal insulin, has the potential to reduce the treatment burden of people with type 2 diabetes who require insulin. We aimed to assess the efficacy and safety of once-weekly efsitora compared with insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin. This phase 3, randomised, 26-week, parallel-design, open-label, treat-to-target, non-inferiority study was done at 78 outpatient clinics and hospitals in Argentina, Germany, India, Italy, Mexico, Spain, and the USA (including Puerto Rico). Participants with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0–10·0%) treated with basal and prandial insulin and up to three non-insulin glucose-lowering agents were randomly assigned (1:1) to efsitora or glargine U100, both with prandial insulin lispro. Randomisation was stratified by country, baseline HbA1c (<8% vs ≥8%; <63·9 mmol/mol vs ≥63·9 mmol/mol), and routine use of personal continuous glucose monitoring or flash glucose monitoring at randomisation (yes vs no). The primary endpoint was HbA1c change from baseline to week 26 (non-inferiority margin 0·4%). The completed trial is registered at ClinicalTrials.gov (NCT05462756). Between Aug 11, 2022, and Feb 27, 2024, 1037 study participants were screened and 730 were randomly assigned to efsitora (n=365) or glargine U100 (n=365). 369 (51%) of 730 participants were female and 361 (49%) were male, the mean participant age was 58·9 years (SD 10·5), and the mean participant BMI was 31·85 kg/m2 (SD 5·47). Using the treatment regimen estimand, the least-squares mean baseline HbA1c was 8·18% (SE 0·04; 65·9 mmol/mol [SE 0·47]) in the efsitora group and 8·18% (0·04; 65·9 mmol/mol [0·47]) in the glargine U100 group. At week 26, the least-squares mean HbA1c was 7·17% (SD 0·05; 54·8 mmol/mol [0·51]) in the efsitora group and 7·18 (0·05; 55·0 mmol/mol [0·51]) in the glargine U100 group. The change from baseline to week 26 using the treatment regimen estimand was –1·01 percentage points for the efsitora group and –1·00 percentage points for the glargine U100 group, indicating non-inferiority of efsitora versus glargine U100. Rates of overall and nocturnal level 2 (<54 mg/dL; 3·0 mmol/L) or level 3 (severe) hypoglycaemia during the treatment period were similar for efsitora versus glargine U100 (6·6 vs 5·9 events per patient-year of exposure, estimated rate ratio [ERR] 1·11, 95% CI 0·85–1·44; p=0·44; 0·67 vs 1·00 events per patient-year of exposure, ERR 0·67, 95% CI 0·44–1·01; p=0·058), respectively. Adverse event occurrence was similar between efsitora and glargine U100. Serious adverse events were reported by 25 (7%) of 365 participants in the efsitora group and 23 (6%) of 365 participants in the glargine U100 group. Efsitora showed non-inferior HbA1c reductions and similar rates of combined clinically significant or severe hypoglycaemia versus glargine U100 in participants with type 2 diabetes treated with basal and prandial insulin. These findings show that efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes. Eli Lilly and Company.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Adults / Adverse events / Aged / Agonists / Blood Glucose / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - drug therapy / Drug Administration Schedule / Female / GLP-1 receptor agonists / Glucose / Glucose monitoring / Glycated Hemoglobin - analysis / Hemoglobin / Humans / Hypoglycemia / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - adverse effects / Insulin / Insulin Glargine - administration & dosage / Insulin Glargine - adverse effects / Insulin Lispro - administration & dosage / Insulin Lispro - adverse effects / Internal Medicine / International organizations / Least squares / Male / Middle Aged / Monitoring / Patients / Pharmacokinetics / Randomization / Telemedicine / Treatment Outcome