BACKGROUND: Once-weekly insulin efsitora alfa (efsitora) is in development for the treatment of people with diabetes. The aim of the current study was to assess the efficacy and safety of once-weekly efsitora compared with daily insulin degludec (degludec) in adults with type 2 diabetes using basal insulin.
METHODS: This randomised, 78-week, phase 3, parallel-design, open-label, treat-to-target, non-inferiority study (QWINT-3) was conducted at 127 sites across nine countries. Adults (aged ≥18 years) with type 2 diabetes currently treated with basal insulin, up to three non-insulin glucose-lowering medications without prandial insulin, and glycated haemoglobin A(HbA) 6·5-10·0% (48-86 mmol/mol) were eligible. Participants were randomly assigned (2:1) to receive efsitora (n=655) or degludec (n=331). The primary endpoint was the change in least-squares mean HbAconcentration from baseline to week 26, assessed in all randomly allocated participants who took at least one dose of study drug (excluding those who discontinued due to inadvertent enrolment), with a non-inferiority margin of 0·4% for efsitora versus degludec. The completed trial is registered at ClinicalTrials.gov (NCT05275400). 1c1c1c
FINDINGS: Between March 8, 2022, and May 15, 2024, 1229 participants were enrolled and 986 (80%) were randomly allocated: 655 to the efsitora group and 331 to the degludec group, all of whom received at least one dose of study treatment. 871 (88%) of those randomly allocated completed 78 weeks of treatment. The population comprised 431 (44%) female and 555 (56%) male patients, median age was 62·0 years (IQR 54·0-68·0), baseline BMI was 29·65 kg/m(IQR 26·32-34·12), and HbAconcentration was 7·7% (7·1-8·4). The least-squares mean change from baseline to week 26 in HbAconcentration was -0·81 percentage points (SE 0·03; -8·85 mmol/mol [0·33]) in the efsitora group and -0·72 percentage points (0·04; -7·88 mmol/mol [0·46]) in the degludec group (estimated treatment difference -0·09 percentage points [95% CI -0·19 to 0·01]), indicating non-inferiority of efsitora to degludec. Combined level 2 hypoglycaemia (glucose concentration <54 mg/dL [<3·0 mmol/L]) or level 3 (severe) hypoglycaemia events from baseline to week 78 occurred at a similar rate for efsitora (0·84 events per patient-year of exposure; 754 events in 268 [41%] participants) and degludec (0·74 per patient-year of exposure; 346 events in 123 [37%] participants; estimated rate ratio 1·14 [95% CI 0·83-1·56]; p=0·43). Serious adverse events occurred in 103 (16%; 7 [1%] related to treatment) efsitora-treated and 37 (11%; 1 [<1%] related to treatment) degludec-treated participants; the most frequent (at ∼1%) were primarily cardiovascular-related in both groups. Nine deaths (seven in the efsitora group and two in the degludec group) occurred during the trial, but none were related to study treatment. 2 1c1c
INTERPRETATION: 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.
FUNDING: Eli Lilly and Company.
