Eli Lilly and Company announced detailed results from three pivotal Phase 3 clinical trials demonstrating that its investigational once-weekly insulin efsitora alfa achieved non-inferior A1C reduction compared to daily basal insulin therapies in adults with type 2 diabetes. The results were presented at the American Diabetes Association 85th Scientific Sessions 2025, with QWINT-1 findings published in The New England Journal of Medicine and QWINT-3 and QWINT-4 results published in The Lancet.
Clinical Trial Results Demonstrate Efficacy Across Patient Populations
The QWINT clinical program enrolled more than 3,000 people with type 2 diabetes across four global registration studies, evaluating efsitora in different patient populations. In QWINT-1, which studied insulin-naïve patients, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine at week 52. The trial utilized a novel fixed-dose escalation approach with only four single-dose titration options: 100 units, 150 units, 250 units, and 400 units administered every four weeks as needed.
QWINT-3 evaluated efsitora in 986 participants currently treated with basal insulin, showing A1C reduction of 0.86% with efsitora compared to 0.75% for insulin degludec at week 26. QWINT-4 studied 730 participants previously treated with both basal and mealtime insulin, demonstrating equivalent A1C reduction of 1.07% for both efsitora and insulin glargine at week 26.
Simplified Dosing Regimen Addresses Treatment Barriers
The fixed-dose regimen employed in QWINT-1 represents a significant departure from traditional insulin management approaches. Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas and lead trial investigator for QWINT-1, emphasized the potential clinical impact: "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."
Participants in QWINT-1 received a starting dose of 100 units of insulin, with escalation to fixed dosages every four weeks until achieving target fasting blood glucose of 80-130 mg/dL. Those with fasting blood glucose greater than 130 mg/dL after 16 weeks were transferred to flexible dosing protocols.
Safety Profile Comparable to Daily Insulin Therapies
Across all three trials, efsitora demonstrated a safety profile similar to commonly used daily basal insulin therapies. Notably, QWINT-1 showed efsitora resulted in approximately 40% fewer hypoglycemic events compared to insulin glargine, with estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of 0.50 with efsitora versus 0.88 with insulin glargine at 52 weeks.
In QWINT-3, hypoglycemic event rates were 0.84 with efsitora versus 0.74 with insulin degludec at 78 weeks. QWINT-4 showed rates of 6.6 with efsitora versus 5.9 with insulin glargine at 26 weeks, reflecting the higher baseline risk in patients using both basal and mealtime insulin.
Molecular Design Enables Weekly Administration
Insulin efsitora alfa is engineered as a fusion protein combining a novel single-chain variant of insulin with a human IgG2 Fc domain. This molecular design enables once-weekly subcutaneous administration while maintaining a low peak-to-trough ratio, potentially providing more stable glucose levels with reduced glucose variability throughout the week.
Jeff Emmick, M.D., Ph.D., senior vice president of product development at Lilly, highlighted the clinical significance: "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."
Regulatory Submission Timeline
Lilly plans to submit efsitora for the treatment of adults with type 2 diabetes to global regulatory agencies by the end of 2025. The comprehensive Phase 3 program, which began in 2022, provides the foundation for these regulatory submissions across multiple patient populations requiring insulin therapy.
The QWINT trials were conducted across multiple countries including the United States, Argentina, Mexico, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain, Taiwan, Germany, India, and Italy, supporting the global development strategy for this once-weekly insulin formulation.
