Efsitora alfa: A New Hope for People with Type 1 Diabetes?
A major international study published in September 2024 in The Lancet could redefine how type 1 diabetes is managed. The QWINT-5 trial, a 52-week, phase 3 randomized trial, investigated efsitora alfa, a once-weekly long-acting insulin analog, as a potential alternative to the current gold standard of daily basal insulin injections.
The study enrolled 692 adults with type 1 diabetes, who were randomized to receive either once-weekly efsitora alfa (n=343) or once-daily degludec (n=349) in combination with mealtime (bolus) insulin. This design reflects real-world insulin therapy, where both basal and bolus components are essential for glucose control.
The appeal of weekly basal insulin is clear: reducing injection burden could improve treatment adherence, lessen emotional fatigue, and make diabetes management more sustainable for many patients. But safety and effectiveness must be rigorously proven-especially when altering fundamental aspects of insulin therapy.
What’s New in QWINT-5?
QWINT-5 is the first phase 3 trial to assess weekly insulin therapy in people with type 1 diabetes-a population that requires highly precise insulin dosing. Unlike in type 2 diabetes, where insulin resistance is dominant, individuals with type 1 diabetes lack endogenous insulin production entirely, making dosing and glucose balance much more sensitive.
The primary endpoint was the change in HbA1c at 26 weeks, a standard marker of long-term glucose control. The results were promising:
- HbA1c change:
–0.51% (efsitora alfa) vs. –0.56% (degludec) - Estimated treatment difference (ETD): 0.05%
- 95% Confidence Interval: –0.08 to +0.18
This confirmed non-inferiority of efsitora alfa compared to degludec in glucose control. Notably, these improvements were maintained through week 52, confirming durability of effect.
Hypoglycemia Risk and Safety
While efficacy was comparable, safety profiles diverged, particularly regarding hypoglycemia, which remains the most feared complication of insulin therapy.
- Combined level 2/3 hypoglycemia was more frequent with efsitora alfa.
- Severe hypoglycemia (level 3) occurred in 10% of patients on efsitora vs. 3% on degludec.
- These events were most concentrated in the first 12 weeks, pointing to the importance of conservative dose titration when initiating therapy.
No deaths or unexpected serious adverse events were reported. Injection-site reactions were infrequent and similar between groups.
Overall, while efsitora alfa was well tolerated, the increased rate of hypoglycemia—particularly early on—warrants close monitoring. Researchers emphasized that starting dose precision and patient education are crucial during the transition.
Study Design Highlights
- Participants: 692 adults with T1D
- Sites: 82 clinical centers across 15 countries
- Trial Duration: 52 weeks
- Trial Registry: ClinicalTrials.gov NCT05463744
- Sponsor: Eli Lilly
- Conflict of Interest: Several authors are Eli Lilly employees
This global study aimed to reflect real-world clinical practice, including patients from diverse regions and healthcare settings.
Practical Implications for Patients
For people with type 1 diabetes, managing the disease involves a lifetime of insulin injections, monitoring, and decisions. The concept of once-weekly basal insulin offers a potentially transformative option-though it’s not a full replacement of daily therapy.
It’s important to clarify:
Basal insulin injections drop from 7 to 1 per week
! But bolus insulin before meals remains necessary
Still, simplifying basal therapy can:
- Reduce injection fatigue
- Improve mental health and treatment satisfaction
- Support patients who struggle with adherence
- Benefit young adults transitioning to self-care
- Help patients in remote areas with limited access to healthcare
In patient-reported outcomes from QWINT-5, many expressed greater convenience and lower daily burden. Yet those with a history of severe hypoglycemia or brittle diabetes should approach weekly therapy cautiously.
Scientific Significance & Next Steps
QWINT-5 provides robust clinical evidence that efsitora alfa is a viable once-weekly option for type 1 diabetes—but not without caveats. While non-inferiority was demonstrated, and tolerability was generally good, the elevated risk of hypoglycemia requires attention.
As of May 2025, efsitora alfa is not yet approved by regulatory bodies. Applications have been submitted to both the FDA and EMA, and review processes are ongoing. If approved, it will likely include specific guidance for dose titration, early monitoring, and patient selection.
Public interest has also grown, with coverage in major outlets. For example,
Reuters
reported on the QWINT-5 findings shortly after publication, noting that a successful rollout could reshape insulin delivery for a global population.
Key Takeaways for Clinicians & Patients
- Efsitora alfa provides comparable glucose control to daily degludec.
- Hypoglycemia is more frequent, especially in early treatment—use caution when initiating.
- Treatment burden is reduced, with potential to improve quality of life.
- Regulatory approvals are pending; not yet available for clinical use.
- Personalization is essential: not all patients will be suitable candidates.
If approved, efsitora alfa will add a new dimension to diabetes care, particularly for those seeking more flexibility and less day-to-day complexity-without compromising glycemic targets.
