Efsitora: Once-Weekly Insulin Proves Comparable to Daily Forms in T2D

In a significant advancement for diabetes management, the investigational insulin analog efsitora alfa has demonstrated noninferior efficacy compared to daily basal insulins in patients with type 2 diabetes (T2D). The findings, presented on June 22, 2025, during the American Diabetes Association's 85th Scientific Sessions in Chicago, stem from three key trials within the QWINT global phase 3 clinical trial program.

The QWINT-1 trial, which focused on insulin-naive individuals, involved 795 participants randomized to receive either once-weekly efsitora via a single-use auto-injector or daily insulin glargine. After 52 weeks, efsitora reduced hemoglobin A1c (A1c) from a baseline of 8.20% to 7.05%, while glargine reduced A1c from 8.28% to 7.08%, thus confirming the noninferiority of efsitora. Lead investigator Dr. Julio Rosenstock, Senior Scientific Advisor for Velocity Clinical Research and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, highlighted the potential of efsitora to simplify insulin therapy initiation and escalation due to its fixed-dose regimen.

In terms of safety, the rate of significant hypoglycemia (defined as blood glucose levels <54 mg/dL) was notably lower in the efsitora group compared to glargine (0.50 vs. 0.88 events per participant-year), further supporting the investigational drug's profile as a viable alternative to daily insulin options.

The QWINT-3 and QWINT-4 trials investigated efsitora against daily insulin degludec and glargine, respectively, in individuals already on insulin therapy. QWINT-3, involving 986 adults, showed a decrease in A1c of 0.81 percentage points for efsitora versus 0.72 for degludec after 78 weeks. Similarly, QWINT-4, which included 730 participants on both basal and prandial insulin, found comparable A1c levels between efsitora and glargine after 26 weeks. However, both QWINT-3 and QWINT-4 noted a higher incidence of mild hypoglycemia with efsitora compared to their daily counterparts.

Despite these promising results, the research is not without limitations. The open-label design of QWINT-1 and the absence of continuous glucose monitoring (CGM) could lead to a potential underestimation of hypoglycemic events, particularly among patients with hypoglycemia unawareness, as noted by Dr. Edith WK Chow and Dr. Elaine Chow of The Chinese University of Hong Kong in their accompanying editorial.

The broader implications of these findings suggest a potential shift in the treatment paradigm for T2D, offering patients a less burdensome insulin administration schedule. However, the adoption of efsitora will depend on factors such as cost, patient preference, and insurance coverage. The emergence of newer noninsulin therapies, notably GLP-1 receptor agonists, may also influence its uptake among patients seeking effective glycemic control with fewer side effects.

As the medical community awaits formal government approval for efsitora, the results from these trials contribute to an evolving landscape in diabetes treatment, illustrating a critical need for patient-centric solutions that enhance adherence and improve health outcomes. With ongoing research, the future of insulin therapy appears promising, potentially offering enhanced options for those living with type 2 diabetes.