Efsitora Alfa (Lilly’s Once-Weekly Insulin) Shows A1C Reduction and Safety Profile Comparable to Daily Insulin in Phase 3 Trials

The QWINT-1, QWINT-3, and QWINT-4 trials bolster confidence in efsitora’s potential to streamline insulin management with once-weekly dosing.

Lilly plans to submit efsitora for regulatory review for adult type 2 diabetes treatment by year-end.

INDIANAPOLIS, June 22, 2025 /PRNewswire/ – Eli Lilly and Company (LLY) today unveiled detailed findings from its Phase 3 QWINT-1, QWINT-3, and QWINT-4 clinical trials. The studies assessed the safety and efficacy of once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes who were either new to insulin, previously used daily basal insulin, or used both daily basal and mealtime insulin. Across all trials, the once-weekly efsitora met its primary endpoint of non-inferior A1C reduction compared to daily basal insulin. The full results were presented at the 85th Scientific Sessions of the American Diabetes Association (ADA) 2025. Simultaneously, the QWINT-1 findings were published in *The New England Journal of Medicine*, while QWINT-3 and QWINT-4 results appeared in *The Lancet*.

In QWINT-1, efsitora lowered A1C by 1.31% compared to 1.27% for insulin glargine at week 52, according to the efficacy estimand.^1,2 Notably, efsitora in this trial utilized a first-of-its-kind fixed-dose regimen, with adjustments made every four weeks based on glucose control.³ QWINT-3 saw efsitora reduce A1C by 0.86% versus 0.75% for insulin degludec at week 26, while in QWINT-4, the reduction was 1.07% for efsitora and 1.07% for insulin glargine at week 26, both according to the efficacy estimand.^4,5 In QWINT-3 and QWINT-4, efsitora was administered using standard insulin dosing adjusted based on individual patient glucose levels.

“The novel fixed-dose approach used in QWINT-1, with its simplified titration options, could revolutionize insulin therapy, making it easier for patients to initiate insulin treatment,” commented Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator for QWINT-1. “A simpler, once-weekly regimen with efsitora could empower individuals with type 2 diabetes to start and maintain insulin therapy to better control blood sugar levels. The consistent results across all QWINT trials demonstrate that once-weekly efsitora effectively controls glucose, comparable to the most popular once-daily basal insulins.”

“Building on Lilly’s legacy of innovation in insulin therapy, once-weekly efsitora may offer a significant shift for individuals with type 2 diabetes requiring insulin, potentially eliminating over 300 injections per year,” stated Jeff Emmick, M.D., Ph.D., senior vice president of product development at Lilly. “These findings reinforce the potential of once-weekly efsitora to reduce the overall burden of insulin therapy through a simplified treatment approach. We are eager to work with regulatory agencies to bring this innovation to patients globally.”

Across the three trials, efsitora showcased a safety profile comparable to standard daily basal insulin therapies for type 2 diabetes. QWINT-1 noted approximately 40% fewer hypoglycemic events with efsitora compared to insulin glargine. The estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure were 0.50 for efsitora and 0.88 for insulin glargine at 52 weeks. In QWINT-3, these rates were 0.84 with efsitora versus 0.74 with insulin degludec at 78 weeks. QWINT-4 showed estimated combined rates of 6.6 for efsitora versus 5.9 for insulin glargine at 26 weeks.

Lilly’s plan to submit efsitora for regulatory approval for adult type 2 diabetes treatment is set for the end of this year.

About the QWINT clinical trial program
The QWINT Phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes commenced in 2022 and involved over 3,000 participants with type 2 diabetes across four global registration studies.

QWINT-1 (NCT05662332) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin using a fixed dose escalation to daily insulin glargine for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 795 participants across the U.S., Argentina and Mexico to receive efsitora once weekly or insulin glargine once daily, administered subcutaneously. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every four weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to daily use of insulin glargine.

QWINT-3 (NCT05275400) was a multicenter, randomized, parallel-design, open-label trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks after a three-week lead-in followed by a five-week safety follow up period, in adults with type 2 diabetes who are currently treated with basal insulin. The trial randomized 986 participants across the U.S., Argentina, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain and Taiwan to receive efsitora once weekly or insulin degludec once daily, administered subcutaneously. The primary objective of the study was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec.

QWINT-4 (NCT05462756) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized 730 participants across the U.S., Argentina, Germany, India, Italy, Mexico, Puerto Rico and Spain to receive efsitora once weekly or insulin glargine once daily, both of which were administered subcutaneously along with insulin lispro. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine.

About insulin efsitora alfa
Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is designed for once-weekly subcutaneous administration, with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week.

About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry, and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.

1. The efficacy estimand represents the treatment effect on all participants who adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia.
2. From a baseline of 8.20% for efsitora and 8.28% for insulin glargine.
3. Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every four weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing.
4. From a baseline of 7.80% for both efsitora and insulin degludec.
5. From a baseline of 8.18% for both efsitora and insulin glargine.
6. The treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation or introduction of rescue therapy for persistent severe hyperglycemia.
7. Blood glucose
8. Nocturnal hypoglycemia was defined as any event that occurred at night between midnight and 6 a.m.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about insulin efsitora alfa as a potential treatment for people with type 2 diabetes and the timeline for future readouts, presentations, and other milestones relating to insulin efsitora alfa and its clinical trials and reflects Lilly’s current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date, that insulin efsitora alfa will prove to be a safe and effective treatment for type 2 diabetes, that insulin efsitora alfa will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly’s expectations, see Lilly’s Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

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