Summary: In 986 adults with type 2 diabetes already treated with basal insulin (QWINT-3, phase 3, open-label, treat-to-target), once-weekly insulin efsitora alfa was non-inferior to once-daily insulin degludec for HbA1c reduction at week 26 (-0.81 vs -0.72 percentage points; estimated treatment difference -0.09 [95% CI -0.19 to 0.01]; non-inferiority margin 0.4%). Combined level 2 or 3 hypoglycaemia rates were similar between groups. The trial demonstrates equivalence, not superiority.
PICO Summary
| Element | Detail |
|---|---|
| Population | 986 randomised adults (median age 62 years, 44% female, baseline HbA1c 7.7%, BMI 29.7 kg/m2) with type 2 diabetes on basal insulin plus up to three non-insulin agents, no prandial insulin; phase 3 RCT across 127 sites in nine countries. |
| Intervention | Once-weekly insulin efsitora alfa, treat-to-target dosing (n=655). |
| Comparison | Once-daily insulin degludec, treat-to-target dosing (n=331); 2:1 randomisation, open-label, 78 weeks. |
| Outcome | Primary: HbA1c change at week 26 -0.81 (SE 0.03) vs -0.72 (SE 0.04) percentage points; estimated treatment difference -0.09 percentage points (95% CI -0.19 to 0.01), within the prespecified 0.4% non-inferiority margin. Level 2/3 hypoglycaemia: 0.84 vs 0.74 events per patient-year (rate ratio 1.14 [95% CI 0.83-1.56]; p=0.43). Serious adverse events 16% vs 11%; nine deaths (seven efsitora, two degludec), none treatment-related. No formal superiority or ARR/NNT applicable (equivalence design). |
Once-weekly efsitora vs degludec (QWINT-3)
RCT · type 2 diabetes · non-inferiority · 26 weeks
Once-weekly efsitora alfa was non-inferior to once-daily degludec for HbA1c lowering, with comparable hypoglycaemia. The benefit is weekly dosing, not better glycaemic control.
Expert Commentary
This trial supports a measured verdict: once-weekly efsitora alfa is non-inferior, not superior, to daily degludec for glycaemic control in basal-insulin-treated type 2 diabetes. The treatment difference of -0.09 percentage points sat comfortably within the 0.4% non-inferiority margin, and hypoglycaemia rates were statistically indistinguishable, so the headline benefit is reduced injection frequency rather than improved efficacy or safety. The principal limitation is the open-label design, which is difficult to avoid given divergent dosing schedules but leaves outcomes that depend on titration behaviour and reporting vulnerable to bias, and a treat-to-target protocol can mask real-world differences. Sponsorship by the manufacturer (Eli Lilly) warrants the usual caution, though the modest, plausibly sized effect and transparent reporting of more serious adverse events (16% vs 11%) and a numerically higher hypoglycaemia rate ratio temper concern about selective framing. Can I use this with my patients? Not yet in routine practice, since efsitora is investigational, but the data suggest it may suit stable basal-insulin users who value weekly dosing once the agent is approved. Confirmatory long-term and cardiovascular safety data, alongside head-to-head comparisons in insulin-naive and prandial-insulin populations, would help clarify where weekly basal insulin belongs.
References
Philis-Tsimikas A, Bergenstal RM, Bailey TS, Jinnouchi H, Thrasher JR, Ilag L, et al. Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial. Lancet. 2025;405(10497):2279-2289. doi:10.1016/S0140-6736(25)01044-X