Insulin Efsitora Alfa Demonstrates A1C Reduction in Various Clinical Trials

In the phase 3 QWINT-1, QWINT-3, and QWINT-4 clinical trials, once-weekly efsitora alfa (efsitora; Eli Lilly and Company) met the primary end point of noninferior hemoglobin A_1C (HbA_1C) reduction compared with daily basal insulin in each trial. The study authors, who presented the results at the American Diabetes Association (ADA) 85th Scientific Sessions 2025, which were also published in the New England Journal of Medicine, noted that the studies assessed the safety and efficacy of efsitora in adults with type 2 diabetes (T2D) who used insulin for the first time, previously used daily basal insulin, and previously used daily basal insulin and mealtime insulin.¹

Image credit: neirfy | stock.adobe.com

"The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, which consisted of only four single-dose titration options, has the potential to facilitate and simplify insulin therapy, reducing the hesitation often associated with starting insulin to treat type 2 diabetes," Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine at the University of Texas Southwestern Medical Center, and lead trial investigator for QWINT-1, said in the news release.¹

Insulin Efsitora Alfa

As a once-weekly basal insulin, efsitora is a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain that is designed for a once-weekly subcutaneous administration.¹

The therapy could provide treatment for individuals with T2D who used basal insulin, a type of long-acting insulin that keeps the glucose levels stable during periods of fasting.²

"Building on Lilly's legacy of innovation in insulin therapy, once-weekly efsitora may offer a significant advancement for people with type 2 diabetes who need insulin by eliminating over 300 injections per year," Jeff Emmick, MD, PhD, senior vice president of product development at Lilly, said in a news release.¹

QWINT Clinical Trial Program

The phase 3 global clinical trial began in 2022 and has included over 3000 individuals with T2D across all of the studies.¹

The QWINT-1 trial (NCT05662332) was a 52-week, open-label, randomized study that compared once-weekly efsitora to once-daily insulin glargine in 795 insulin-naïve adults with T2D. Individuals on efsitora followed a fixed-dose escalation to a fasting blood glucose target of 80 to 130 mg/dL, with flexible dosing after 16 weeks if needed. The primary objective was to demonstrate efsitora’s non-inferiority to insulin glargine in reducing HbA_1C at week 52.¹

The QWINT-3 trial (NCT05275400) was a 78-week, multicenter, open-label, randomized study comparing once-weekly efsitora to once-daily insulin degludec in 986 adults with T2D currently on basal insulin, followed by a 5-week safety follow-up. The primary objective was to demonstrate efsitora’s non-inferiority to insulin degludec in reducing HbA_1C at week 26.¹

The QWINT-4 trial (NCT05462756) was a 26-week, open-label, randomized controlled study comparing once-weekly efsitora with once-daily insulin glargine—both alongside insulin lispro—in 730 individuals with T2D previously on basal insulin and multiple mealtime insulin injections. The primary objective was to demonstrate efsitora’s noninferiority to insulin glargine in reducing HbA_1C at week 26.¹

QWINT Clinical Trial Results

Results from QWINT-1 revealed that efsitora reduced HbA_1C by 1.31% compared to 1.2% for insulin glargine at week 52 for the efficacy estimand. In QWINT-3, HbA_1C was reduced by 0.86% with efsitora compared to 0.75% for insulin degludec at week 26 for the efficacy estimand. Lastly, in QWINT-4, efsitora and insulin glargine reduced HbA_1C by 1.07% at week 26 for the efficacy estimand.¹

The overall safety profile was similar to commonly used daily basal insulin therapies across all 3 studies, with hypoglycemic events that were compared to insulin glargine.¹

"A simpler, once-weekly regimen with efsitora may help people with type 2 diabetes initiate and manage insulin therapy with the goal of improving blood sugar levels. Across all QWINT trials, the results showed that once-weekly efsitora controlled glucose as effectively as the most popular once-daily basal insulins,” Rosenstock concluded in the news release.¹

REFERENCES

1. Lilly's once-weekly insulin efsitora alfa demonstrated A1C reduction and a safety profile consistent with daily insulin in multiple Phase 3 trials. Eli Lilly and Company. News release. June 22, 2025. Accessed July 17, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-once-weekly-insulin-efsitora-alfa-demonstrated-a1c

2. Type 2 Diabetes. Mayo Clinic. News release. February 27, 2025. Accessed July 17, 2025. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193

3. Basal Insulin Types, Benefits, Dosage Information, and Side Effects. Healthline. News release. Updated February 13, 2023. Accessed July 17, 2025. https://www.healthline.com/health/type-2-diabetes/basal-insulin-types-benefits-dosage-side-effects