In a first-of-its-kind fixed dose study, once weekly insulin efsitora alfa leads to A1C reduction similar to daily insulin

In these long-term treat-to-target trials, efsitora showed non-inferior A1C reduction compared to the most frequently used daily basal insulins globally.

"Once weekly insulins, like efsitora, have the potential to transform diabetes care as we know it," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Many patients are reluctant to start insulin because of the burden it places on them. With a simple fixed-dose regimen, once-weekly efsitora could make it easier for people with diabetes to start and manage insulin therapy, while reducing the impact it has on their day-to-day lives."

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 doses 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 estimand, (the efficacy estimand represents the treatment effect had all participants adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia), efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine, resulting in an A1C of 6.92% and 6.96%, respectively. For the treatment-regimen estimand (tThe efficacy estimand represents the treatment effect had all participants adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia), efsitora reduced A1C by 1.19% compared to 1.16% for insulin glargine, resulting in an A1C of 7.05% and 7.08%, respectively.

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 estimand, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec resulting in an A1C of 6.93% and 7.03%, respectively. For the treatment-regimen estimand, efsitora reduced A1C by 0.81% compared to 0.72% for insulin degludec resulting in an A1C of 6.99% and 7.08%, respectively.

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 estimand, participants taking efsitora spent 62.8% of time in range compared to 61.3% for insulin degludec for weeks 22-26. For the treatment-regimen estimand, participants taking efsitora spent 61.4% of time in range compared to 61% for insulin degludec. 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 22-26.

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.>

Detailed results for QWINT-1 and QWINT-3 will be shared at an upcoming congress and published in a peer-reviewed journal. Additionally, detailed results for QWINT-2 and QWINT-5 will be presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024.