Eli Lilly and Company (NYSE:LLY) today announced positive topline results from the QWINT-1 and QWINT-3 phase 3 clinical trials evaluating once weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes using basal insulin for the first time (insulin naïve) and in those who have switched from daily basal insulin injections, respectively. In these long-term treat-to-target trials, efsitora showed non-inferior A1C reduction compared to the most frequently used daily basal insulins globally.

QWINT-1 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin glargine for 52 weeks. The trial randomized adults with type 2 diabetes who are insulin naïve to receive either efsitora once weekly in a single-use autoinjector or insulin glargine once daily. Efsitora was titrated across four fixed doses1 at four-week intervals, as needed for blood glucose control. The study's goal was to provide data supporting real-life applications of fixed dose regimens, which have the potential to make it easier for people living with diabetes to start and manage insulin therapy.

The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin glargine at week 52. For the efficacy estimand2,3, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine, resulting in an A1C of 6.92% and 6.96%, respectively4. For the treatment-regimen estimand5,6, efsitora reduced A1C by 1.19% compared to 1.16% for insulin glargine, resulting in an A1C of 7.05% and 7.08%, respectively4.

QWINT-3 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin degludec for 78 weeks in adults with type 2 diabetes currently treated with basal insulin. Participants were randomized 2:1 to receive either efsitora once weekly or insulin degludec once daily.

The QWINT-3 trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin degludec at week 26. For the efficacy estimand7, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec resulting in an A1C of 6.93% and 7.03%, respectively8. For the treatment-regimen estimand9, efsitora reduced A1C by 0.81% compared to 0.72% for insulin degludec resulting in an A1C of 6.99% and 7.08%, respectively10.

Additionally, participants taking efsitora or insulin degludec spent approximately two hours more time in range (glucose 70-180 mg/dL) per day for weeks 22-26 compared to baseline. For the efficacy estimand11, participants taking efsitora spent 62.8% of time in range compared to 61.3% for insulin degludec for weeks 22-2612. For the treatment-regimen estimand13, participants taking efsitora spent 61.4% of time in range compared to 61% for insulin degludec14. Further, for the efficacy estimand, participants taking efsitora spent 38.3% of time in tight range (glucose 70-140 mg/dL) compared to 36.8% for insulin degludec for weeks 22-2615.

In both QWINT-1 and QWINT-3, the overall safety and tolerability profile of efsitora was similar to that of daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure from weeks 0-52 were 0.50 with efsitora vs. 0.88 with insulin glargine – approximately 40% lower with efsitora than insulin glargine. In QWINT-3, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure from weeks 0-78 were 0.84 with efsitora vs. 0.74 with insulin degludec.