Eli Lilly announced positive topline results from its phase 3 clinical trial program evaluating efsitora alfa, a once-weekly basal insulin for adults with type 2 diabetes. The therapy met both primary and key secondary endpoints in two separate treat-to-target studies, demonstrating non-inferior A1C reduction compared to commonly used daily basal insulins.
Clinical Trial Results
QWINT-2 Study in Insulin-Naïve Patients
The QWINT-2 trial was a parallel-design, open-label, randomized, controlled phase 3 study that included 928 insulin-naïve adults with type 2 diabetes. Participants were randomly assigned to receive either efsitora once weekly or insulin degludec once daily for 52 weeks.
Efsitora achieved its primary endpoint of non-inferior A1C reduction compared to insulin degludec at week 52. The therapy reduced A1C by 1.34% compared to 1.26% for insulin degludec. Additionally, patients treated with efsitora spent 45 minutes more time in range and 37 minutes more in tight range without additional time in hypoglycemia.
The study also assessed efficacy in patients using and not using GLP-1 receptor agonists. Efsitora met its key secondary endpoint of non-inferior A1C change compared to insulin degludec among patients in both groups.
QWINT-4 Study in Insulin-Experienced Patients
QWINT-4 evaluated efsitora in adults with type 2 diabetes who had already been treated with basal insulin and at least two injections per day of prandial insulin. This parallel-design, open-label, randomized, controlled phase 3 study compared efsitora once weekly to insulin glargine once daily for 26 weeks.
Both treatment groups achieved identical A1C reductions of 1.07% from baseline to week 26, with efsitora meeting its primary endpoint of non-inferior A1C reduction compared to insulin glargine.
Safety Profile
Efsitora demonstrated a favorable safety profile in both trials. The estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure were 0.58 in the overall program. Specifically, in QWINT-2, the rate was 0.58 events per patient-year with efsitora compared to 0.45 events with insulin degludec. In QWINT-4, the rate was 6.6 events per patient-year with efsitora versus 5.9 events with insulin glargine.
Clinical Significance
"The results of QWINT-2 and QWINT-4 are a significant milestone for the diabetes community and demonstrate that efsitora as a weekly insulin provides blood sugar control equivalent to daily basal insulins," said Jeff Emmick, MD, PhD, senior vice president of product development at Eli Lilly. "With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces treatment burden of traditional daily injections and potentially improves adherence for people with diabetes."
Addressing Treatment Challenges
Research indicates that 20% to 25% of patients with type 2 diabetes require insulin therapy. However, many patients do not achieve adequate metabolic control following insulin initiation due to factors including therapeutic inertia, fear of hypoglycemia, poor communication, and the burden of multiple daily injections. Once-weekly insulin injections may allow patients to have better control over their diabetes through simplified therapy.
According to research published in Diabetologia, "For the first time there is an opportunity to make an important breakthrough in basal insulin therapy, particularly in people with type 2 diabetes, and to improve not only the quality of life of people with diabetes, but also the practice of diabetologists."
Future Presentations and Timeline
Detailed results from the QWINT-2 study will be presented at the 2024 European Association for the Study of Diabetes (EASD) Annual Meeting. Topline results from additional trials in the QWINT program, including QWINT-1, QWINT-3, and QWINT-5, are expected later in 2024.
