Eli Lilly's insulin efsitora alfa, a novel once-weekly basal insulin, has shown promising results in multiple Phase 3 clinical trials for both type 1 and type 2 diabetes. The QWINT program, encompassing five global registration studies, aims to establish the non-inferiority of efsitora compared to daily insulin injections in managing blood sugar levels. These findings, presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024 and published in journals like The Lancet and The New England Journal of Medicine, suggest a potential shift in diabetes management by reducing the frequency of injections.
Efficacy in Type 2 Diabetes
In insulin-naïve adults with type 2 diabetes, the QWINT-1 trial compared efsitora to daily insulin glargine over 52 weeks. Results indicated that efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine, demonstrating non-inferiority. Similarly, the QWINT-3 trial, involving adults with type 2 diabetes already treated with basal insulin, found that efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec over 26 weeks, again meeting the non-inferiority endpoint. Jeff Emmick, MD, PhD, senior vice president, product development, Lilly, noted that "Once weekly insulins, like efsitora, have the potential to transform diabetes care as we know it," potentially easing the burden for patients reluctant to start insulin therapy.
In the QWINT-2 trial, efsitora reduced A1C by 1.34% compared to 1.26% for insulin degludec, resulting in A1C levels of 6.87% and 6.95%, respectively, at 52 weeks. Participants taking efsitora also achieved 45 minutes more time in range per day without additional time in hypoglycemia compared to insulin degludec.
Outcomes in Type 1 Diabetes
The QWINT-5 trial assessed efsitora against daily insulin degludec in adults with type 1 diabetes. At 26 weeks, efsitora demonstrated a non-inferior HbA1c reduction compared to insulin degludec (-0.51% vs -0.56%, respectively). However, rates of combined level 2 (<54 mg/dL) or level 3 severe hypoglycemia were higher with efsitora (14.03 vs 11.59 events per patient-year of exposure; estimated rate ratio 1.21, 95% CI 1.04 to 1.41; p=0.016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycemia incidence was also higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. These findings suggest a need for further evaluation of efsitora dose initiation and optimization in people with type 1 diabetes.
Safety and Tolerability
In type 2 diabetes trials, the safety profile of efsitora was generally similar to that of daily basal insulins. In QWINT-1, the estimated combined rates of severe or clinically significant hypoglycemic events were approximately 40% lower with efsitora compared to insulin glargine. However, the type 1 diabetes trial (QWINT-5) revealed a higher incidence of hypoglycemia with efsitora, indicating a need for careful dose adjustment and patient monitoring in this population.
Potential Impact on Diabetes Management
The introduction of a once-weekly insulin could significantly impact diabetes management by simplifying treatment regimens and potentially improving patient adherence. As Carol Wysham, M.D., clinical professor of medicine at the University of Washington School of Medicine, stated, "Efsitora has the potential to address treatment burden and improve adherence -- all while lowering A1C," offering a convenient option for individuals seeking similar outcomes to daily insulins. With detailed results from the QWINT program expected to be published in peer-reviewed journals, efsitora represents a promising advancement in diabetes care.
