Summary: In 730 adults with type 2 diabetes already treated with basal and prandial insulin (QWINT-4), once-weekly insulin efsitora alfa was non-inferior to once-daily insulin glargine U100 for the primary endpoint of HbA1c change at week 26 (-1.01 vs -1.00 percentage points; non-inferiority margin 0.4%). Rates of clinically significant or severe hypoglycaemia were similar between groups, with no demonstrated superiority on glycaemic control.
PICO Summary
| Element | Detail |
|---|---|
| Population | 730 adults with type 2 diabetes (HbA1c 7.0-10.0%) treated with basal and prandial insulin; phase 3, open-label, treat-to-target, multicentre (78 sites across Argentina, Germany, India, Italy, Mexico, Spain, and the USA including Puerto Rico). |
| Intervention | Once-weekly insulin efsitora alfa with prandial insulin lispro (n=365). |
| Comparison | Once-daily insulin glargine U100 with prandial insulin lispro (n=365). |
| Outcome | Primary endpoint (HbA1c change, baseline to week 26): -1.01 percentage points (efsitora) vs -1.00 (glargine), meeting the prespecified non-inferiority margin of 0.4%; week-26 HbA1c 7.17% vs 7.18%. Overall level 2 or 3 hypoglycaemia: 6.6 vs 5.9 events per patient-year (ERR 1.11, 95% CI 0.85-1.44; p=0.44). Nocturnal level 2 or 3 hypoglycaemia: 0.67 vs 1.00 events per patient-year (ERR 0.67, 95% CI 0.44-1.01; p=0.058). Serious adverse events: 25 (7%) vs 23 (6%). Superiority was not demonstrated and no absolute risk reduction or NNT applies to this equivalence design. |
QWINT-4: Weekly Efsitora vs Daily Glargine
RCT · type 2 diabetes · 26 weeks
Once-weekly efsitora was non-inferior to daily glargine for HbA1c reduction, with similar hypoglycaemia. The benefit is fewer basal injections, not better control.
Expert Commentary
QWINT-4 was designed as a non-inferiority comparison, and that is exactly what it delivered: once-weekly efsitora matched daily glargine on HbA1c reduction without a superiority claim, and the two regimens behaved similarly on hypoglycaemia and serious adverse events. The verdict is therefore measured rather than transformative; the appeal of efsitora lies in reducing basal injections from seven to one per week, not in better glucose control. The principal limitation is the open-label design, which is unavoidable given the divergent dosing schedules but leaves patient-reported and behavioural outcomes vulnerable to expectation bias, and HbA1c-related endpoints were assessed over only 26 weeks. The trial was funded by the manufacturer, several authors are company employees, and the equivalence framing means the result should be read as parity, not advantage. Can I use this with my patients? Potentially yes, for a selected adult with type 2 diabetes on a stable basal-prandial regimen who is well controlled but burdened by daily basal injections and motivated to simplify dosing, provided prandial insulin and titration support remain in place. It is not a tool for chasing tighter targets, and longer-term safety and durability data would strengthen confidence. Independent, longer comparative trials and real-world adherence data are now warranted before once-weekly basal insulin is positioned as a default option.
References
Blevins T, Dahl D, Perez Manghi FC, Murthy S, Ortiz Carrasquillo R, Li X, et al. Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial. Lancet. 2025;405(10497):2290-2301. doi:10.1016/S0140-6736(25)01069-4