Key Takeaways
- Once-weekly efsitora matches daily insulin efficacy: Phase III QWINT trials confirmed that efsitora achieved non-inferior A1C reductions compared to once-daily basal insulin in type 2 diabetes patients.
- Simplified dosing may ease insulin initiation: The fixed-dose escalation strategy used in QWINT-1 could help overcome barriers to starting insulin therapy by reducing injection frequency and complexity.
- Comparable safety with fewer hypoglycemic events: Efsitora demonstrated a similar safety profile to insulin glargine and degludec, with lower or similar rates of hypoglycemia across all three trials.
Results from the Phase III QWINT-1, QWINT-3, and QWINT-4 trials show that Eli Lilly’s investigational once-weekly insulin efsitora alfa demonstrated non-inferior A1C reduction compared to once-daily basal insulin in adults with type 2 diabetes. QWINT-1 evaluated efsitora in insulin-naïve patients, QWINT-3 evaluated those previously on basal insulin, and QWINT-4 evaluated those using both basal and mealtime insulin.1
Can a Once-Weekly Insulin Match the Effectiveness of Daily Injections?
"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," QWINT-1 lead trial investigator Julio Rosenstock, senior scientific advisor, Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, in a press release. "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."
QWINT-1: Evaluating Efsitora in Insulin-Naïve Patients
The parallel-design, open-label, treat-to-target, randomized, controlled QWINT-1 trial compared the efficacy and safety of once-weekly efsitora using fixed-dose escalation to daily insulin glargine over 52 weeks in 795 patients.
- Patients were randomly assigned to receive either efsitora once weekly or insulin glargine once daily, administered subcutaneously (SC).
- Participants started efsitora at 100 units with fixed dose escalations every four weeks up to 400 units to reach a fasting blood glucose target of 80–130 mg/dL, switching to flexible dosing if levels remained above 130 mg/dL after 16 weeks.
- The primary endpoint of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to daily use of insulin glargine.
- Results showed that efsitora achieved a 1.31% A1C reduction at week 52, nearly identical to glargine’s 1.27%.
QWINT-3: Head-to-Head with Insulin Degludec
- The multicenter, randomized, parallel-design, open-label QWINT-3 trial compared the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks in 986 patients.
- Patients were randomly assigned to receive either SC efsitora once weekly or insulin degludec once daily.
- The primary endpoint of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec.
- Results showed A1C reductions of 0.86% for efsitora and 0.75% for degludec at week 26.
QWINT-4: Efsitora in Patients Using Basal and Mealtime Insulin
- The parallel-design, open-label, treat-to-target, randomized, controlled QWINT-4 trial compared the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in 730 adults with type 2 diabetes previously treated with basal insulin and at least two injections per day of mealtime insulin.
- Patients were randomly assigned to receive SC efsitora once weekly or insulin glargine once daily in addition to insulin lispro.
- The primary endpoint of the trial was non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine.
- Results showed a 1.07% A1C drop for both efsitora and glargine at week 26, with numerically lower hypoglycemia rates for efsitora.
- Notably, nearly 40% of efsitora-treated participants in QWINT-4 reached A1C targets without nocturnal hypoglycemia.
Comparable Safety with Fewer Injections
Across all three trials, efsitora demonstrated a safety profile comparable to two widely used daily basal insulins. In QWINT-1, efsitora was associated with approximately 40% fewer hypoglycemic events than insulin glargine, with event rates of 0.50 versus 0.88 per patient-year at 52 weeks. In QWINT-3, event rates were 0.84 for efsitora and 0.74 for degludec at 78 weeks. In QWINT-4, rates were 6.6 for efsitora compared to 5.9 for glargine at 26 weeks.1
