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Lilly Announces Positive Phase 3 Results for Once-Weekly Insulin Efsitora Alfa at ADA 2025, Plans Global NDA Submission by Year-End

Jun 23, 2025 09:06 CST Updated 09:06
Eli Lilly

Global Pharmaceutical R&D and Production Company


  • Fixed-dose QWINT-1 study, as well as QWINT-3 and QWINT-4 study results, all indicate that efsitora can simplify insulin therapy through a once-weekly formulation.


  • Eli Lilly Plans to Submit Efsitora for Regulatory Approval in Major Markets Worldwide by the End of This Year for the Treatment of Adult Patients with Type 2 Diabetes


On June 22, 2025, Eli Lilly announced detailed results from the QWINT-1, QWINT-3, and QWINT-4 Phase 3 clinical trials. These studies evaluated the efficacy and safety of once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes (T2DM): those initiating insulin therapy for the first time, those previously using daily basal insulin, and those previously on a combination of basal and mealtime insulin. All studies met their primary endpoint, demonstrating that once-weekly efsitora was non-inferior to once-daily basal insulin in reducing glycated hemoglobin (A1C) levels. Full results of these studies were presented at the 85th Scientific Sessions of the American Diabetes Association (ADA). Notably, findings from the pioneering fixed-dose study QWINT-1 were simultaneously published in The New England Journal of Medicine, while results from QWINT-3 and QWINT-4 were concurrently published in The Lancet.


Statement:

1. Insulin efsitora alfa (efsitora) is an investigational drug and has not been approved in China.

2. Eli Lilly does not recommend the use of any unapproved drugs/indications.


In the QWINT-1 study, the efficacy estimand showed that at Week 52, the efsitora group had a 1.31% reduction in A1C, while the insulin glargine group had a 1.27% reduction.1,2In the study, efsitora was titrated every 4 weeks using four fixed doses based on blood glucose control.3In the QWINT-3 study, the efficacy estimand showed that at week 26, A1C decreased by 0.86% in the efpeglenatide group and by 0.75% in the degludec insulin group.4In the QWINT-4 study, the efficacy estimand showed that at week 26, A1C decreased by 1.07% in both the efsitora group and the insulin glargine group.5In the QWINT-3 and QWINT-4 studies, efsitora was administered using a flexible insulin dosing adjustment method based on glycemic control.


Dr. Julio Rosenstock, Principal Investigator of QWINT-1, Scientific Advisor at Velocity Clinical Research in Dallas City Medicine, and Professor of Clinical Medicine at the University of Texas Southwestern Medical CenterIndicates:

QWINT-1 adopts an innovative once-weekly fixed-dose efsitora treatment regimen, consisting of four fixed doses, which is expected to simplify the insulin therapy process and eliminate concerns for type 2 diabetes patients initiating insulin therapy. This convenient weekly regimen may help patients start and manage insulin therapy more smoothly, thereby achieving the goal of blood glucose improvement. All QWINT studies have shown that the blood glucose control effect of efsitora is comparable to the most commonly used daily basal insulin.


Primary Endpoint of QWINT-1


QWINT-3 Primary Endpoint and Key Secondary Endpoint


QWINT-4 Primary Endpoint and Key Secondary Endpoint


Dr. Jeff Emmick, Senior Vice President of Product Development at Eli Lilly and CompanyIndicates:

For a long time, Eli Lilly and Company has been deeply engaged in the field of insulin therapy and continuously leading innovation. Efsitora, administered once a week, has the potential to bring significant breakthroughs to patients with type 2 diabetes in need of insulin treatment—reducing more than 300 injections per year. The results of this study indicate that simplifying the treatment process with efsitora, a weekly formulation, will help alleviate the overall burden brought by insulin therapy. We will collaborate with global regulatory agencies to make this innovative therapy accessible to patients worldwide.


In the three clinical studies mentioned above, the safety of efsitora was similar to that of the two most commonly used daily basal insulins in current T2DM treatment. In the QWINT-1 study, the proportion of hypoglycemic events in the efsitora group was 40% lower than that in the insulin glargine group; at week 52, the estimated combined incidence rates of severe or clinically significant hypoglycemic events were 0.50 (patients/year) in the efsitora group and 0.88 (patients/year) in the insulin glargine group. In the QWINT-3 study, the incidence rate of these events at week 78 was 0.84 (patients/year) in the efsitora group and 0.74 (patients/year) in the insulin degludec group. In the QWINT-4 study, at week 26, the estimated combined incidence rates of severe or clinically significant hypoglycemic events were 6.6 (patients/year) in the efsitora group and 5.9 (patients/year) in the insulin glargine group.


Eli Lilly plans to submit an application for efsitora to treat adult patients with T2DM to global regulatory authorities by the end of this year.


About the QWINT Series of Clinical Trials

The QWINT Phase 3 global clinical development program was launched in 2022, which includes four global registration studies and has recruited over 3,000 patients with T2DM globally.


QWINT-1 (NCT05662332) is a 52-week, parallel-design, open-label, treat-to-target, randomized controlled trial aimed at comparing the efficacy and safety of once-weekly fixed-dose basal insulin efsitora with insulin glargine in adult T2DM patients naive to insulin therapy. The trial enrolled 795 participants, randomly assigned to either once-weekly efsitora or once-daily insulin glargine treatment groups, from the United States, Argentina, and Mexico. All participants receiving efsitora started with an initial dose of 100 units of insulin, which was then gradually increased every 4 weeks as needed to fixed doses of 150 units, 250 units, or 400 units to achieve a fasting blood glucose target of 4.4-7.2 mmol/L. From week 16 onward, participants with fasting blood glucose levels exceeding 7.2 mmol/L were transitioned to flexible dose adjustments. The primary objective of the trial is to demonstrate the non-inferiority of efsitora compared to insulin glargine in reducing A1C levels at week 52.


QWINT-3 (NCT05275400) is a 78-week, parallel-design, open-label, treat-to-target, randomized controlled trial aimed at comparing the efficacy and safety of once-weekly basal insulin efsitora with degludec insulin in adult T2DM patients currently receiving basal insulin therapy, followed by a five-week safety follow-up after the treatment period. The trial enrolled 986 participants, randomly assigned to either once-weekly efsitora or once-daily degludec insulin treatment groups, from the United States, Argentina, Hungary, Japan, South Korea, Poland, Puerto Rico, Slovakia, Spain, and Taiwan, China. The primary objective of the study is to demonstrate the non-inferiority of efsitora compared to degludec insulin in reducing A1C levels at 26 weeks.


QWINT-4 (NCT05462756) is a 26-week, parallel-design, open-label, treat-to-target, randomized controlled trial aimed at comparing the efficacy and safety of once-weekly basal insulin efsitora with insulin glargine in adult patients with T2DM who were previously treated with basal insulin and received at least two daily mealtime insulin injections. The trial enrolled 730 participants, randomly assigned to receive either once-weekly efsitora or once-daily insulin glargine, both in combination with insulin lispro. Participants were recruited from the United States, Argentina, Germany, India, Italy, Mexico, Puerto Rico, and Spain. The primary objective of the study is to demonstrate the non-inferiority of efsitora compared to insulin glargine in reducing A1C levels at 26 weeks.


About Efsitora Alfa Insulin

Efsitora alfa (Efsitora), a once-weekly basal insulin, is a fusion protein that combines a novel single-chain insulin variant with the human lgG2-Fc domain. It is designed for once-weekly subcutaneous injection, offering a lower peak-to-trough ratio and more stable glycemic control (reduced glycemic variability) over the course of a week.


References


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  1. The efficacy estimand represents all participants who continue to use the study drug and do not initiate persistent severe hyperglycemia rescue therapy.

  2. The A1C baselines for participants in the Efsitora and insulin glargine treatment groups were 8.20% and 8.28%, respectively.

  3. Participants receiving efsitora started with an initial dose of 100 units of insulin, followed by titration to fixed doses of 150 units, 250 units, and 400 units every 4 weeks as needed, until the target fasting blood glucose level of 4.4-7.2 mmol/L was achieved. Participants with fasting blood glucose levels exceeding 7.2 mmol/L at or after 16 weeks will be switched to flexible dose adjustments.

  4. The A1C baseline for participants in the Efsitora and degludec insulin treatment groups was 7.80%.

  5. The A1C baseline for participants in the Efsitora and insulin glargine treatment groups was 8.18%.

  6. The treatment strategy estimand represents the average effectiveness estimate for participants, regardless of whether they adhere to the study medication or receive rescue treatment for persistent severe hyperglycemia.

  7. Blood glucose < 3.0 mmol/L.

  8. Nocturnal hypoglycemia refers to any adverse event occurring between midnight and 6 a.m.


Lilly

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Lilly

About Eli Lilly and Company

Eli Lilly and Company is a pharmaceutical company dedicated to improving human health through scientific innovation and benefiting patients worldwide. As a leader in the healthcare industry, Eli Lilly and Company has nearly 150 years of history. Today, our medicines have helped tens of millions of people around the world. Harnessing the power of biotechnology, chemistry, and genomic medicine, our scientists are actively advancing new medical breakthroughs to address severe global health challenges. Redefining therapies for diabetes and obesity, reducing the long-term impact of obesity on the body; supporting initiatives for the prevention and treatment of Alzheimer's disease; providing solutions for a range of immune-mediated diseases that threaten human health; and transforming difficult-to-treat cancers into manageable conditions. Every step Eli Lilly and Company takes toward a healthier world is driven by our belief in "making life better for millions of patients." This includes innovative clinical trials aimed at addressing multiple global challenges, while ensuring the accessibility and affordability of medicines. For more information about Eli Lilly and Company, please visit: www.lilly.com.cn.


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