BACKGROUND: Insulin efsitora alfa (efsitora) is a new basal insulin designed for once-weekly administration. Data on safety and efficacy have been limited to small, phase 1 or phase 2 trials.
METHODS: We conducted a 52-week, phase 3, parallel-design, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive efsitora or degludec. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; we hypothesized that efsitora would be noninferior to degludec (noninferiority margin, 0.4 percentage points). Secondary and safety end points included the change in the glycated hemoglobin level in subgroups of participants using and not using glucagon-like peptide-1 (GLP-1) receptor agonists, the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter in weeks 48 through 52, and hypoglycemic episodes.
RESULTS: A total of 928 participants underwent randomization (466 to the efsitora group and 462 to the degludec group). The mean glycated hemoglobin level decreased from 8.21% at baseline to 6.97% at week 52 with efsitora (least-squares mean change, -1.26 percentage points) and from 8.24% to 7.05% with degludec (least-squares mean change, -1.17 percentage points) (estimated treatment difference, -0.09 percentage points; 95% confidence interval [CI], -0.22 to 0.04), findings that showed noninferiority. Efsitora was noninferior to degludec with respect to the change in the glycated hemoglobin level in participants using and not using GLP-1 receptor agonists. The percentage of time that the glucose level was within the target range was 64.3% with efsitora and 61.2% with degludec (estimated treatment difference, 3.1 percentage points; 95% CI, 0.1 to 6.1). The rate of combined clinically significant or severe hypoglycemia was 0.58 events per participant-year of exposure with efsitora and 0.45 events per participant-year of exposure with degludec (estimated rate ratio, 1.30; 95% CI, 0.94 to 1.78). No severe hypoglycemia was reported with efsitora; six episodes were reported with degludec. The incidence of adverse events was similar in the two groups.
CONCLUSIONS: In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora was noninferior to once-daily degludec in reducing glycated hemoglobin levels. (Funded by Eli Lilly; QWINT-2 ClinicalTrials.gov number, NCT05362058.).
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Endocrine | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
Useful information to support the safety and non-inferiority of once-weekly insulin in a highly controlled clinical trial setting. We will need to watch for real-world data on potentially higher risks of adverse effects such as hypoglycemia in less controlled settings.
The results of the phase 3 QWINT-2 trial are of utmost importance for the future management of type 2 diabetes in individuals with difficult-to-treat diabetes. Once-weekly insulin regimens appear to be equally efficacious and safe with established currently used once-daily basal insulin regimens. I think the results of these trials will change the therapeutic landscape of type 2 diabetes within the next few years, especially since insulin efsitora proves to be cardiovascular safe.
This is a highly informative article. Although it is more convenient to use once weekly instead of once daily, non-inferiority research is not sufficient for a new product and superiority trials are mandatory.
A non-inferiority study showing insulin efsitora (once weekly injection) is non-inferior to degludec (once daily) for reducing A1c. From a hospitalist standpoint, it's good to be aware of new insulins that may be longer acting, as that will guide our initial choices when doing the med recommendation (if on efsitora, for example, there may not be a need for qHS dosing for lantus or glargine until the efsitora expires).
Very promising trial regarding weekly vs daily insulin injections in type 2 diabetes.
