Weekly basal insulin efsitora effective for managing type 2 diabetes

1. In patients with type 2 diabetes mellitus (T2DM) who had not previously been on insulin therapy, once-weekly fixed-dose insulin efsitora was noninferior to daily insulin glargine in reducing glycated hemoglobin (HbA1c) levels by 52 weeks.

2. Insulin efsitora was associated with less clinically significant hypoglycemia and lower total weekly insulin dose, compared to insulin glargine.

Evidence Rating Level: 1 (Excellent)

Study Rundown: T2DM is an increasingly prevalent metabolic disorder worldwide. Adequate glycemic control is paramount in reducing the risk of T2DM-associated complications, including cardiovascular adverse events and mortality. Insulin therapy, including basal insulin, is recommended for patients in whom non-insulin treatment has been inadequate. Basal dose-adjusted insulin carries a high daily injection burden and potential delayed therapy intensification. Insulin efsitora is a novel fixed-dose basal insulin with once-weekly administration. This trial assessed insulin efsitora against daily insulin glargine among T2DM patients who had not been on prior insulin therapy. Insulin efsitora dose was adjusted every four weeks according to fasting blood glucose targets. By 52 weeks, insulin efsitora was noninferior to insulin glargine in reducing the mean HbA1c levels, without demonstrated superiority. However, clinically significant or severe hypoglycemia occurred less frequently with insulin efsitora, and the mean total weekly insulin dose was also lower. The study was limited by its intrinsic open-label design and lack of continuous glucose monitoring. Nevertheless, these results demonstrated the noninferiority of once weekly efsitora insulin compared to daily glargine in reducing HbA1c levels in patients with T2DM.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This was a treat-to-target, randomized controlled trial investigating once-weekly fixed-dose insulin efsitora in patients with T2DM without previous insulin therapy. Patients aged 18 or older with T2DM, who had not previously received insulin therapy, had a HbA1c level 7.0-10.0% and a body-mass index ≤45.0, and had been on stable non-insulin glucose-lowering therapies for at least three months, were eligible for inclusion. Key exclusion criteria included hemoglobinopathies affecting HbA1c measurements, diabetes cases other than T2DM, severe heart failure, history of recent severe hypoglycemia, ketoacidosis or hyperosmolar state requiring hospitalization, and significant weight changes in the preceding 3 months. A total of 795 patients were randomized 1:1 to receive either subcutaneous once-weekly insulin efsitora (efsitora group) or once-daily insulin glargine U100 (glargine group). The primary outcome was change from baseline in HbA1c at 52 weeks, tested for noninferiority. By week 52, the least-squares mean change of mean HbA1c from baseline was -1.19 percentage points (pp) for the efsitora group and -1.16pp for the glargine group (estimate between-group difference [EBGD] -0.03pp, 95% confidence interval [CI] -0.18 to 0.12), demonstrating noninferiority of efsitora to glargine. Superiority criterion, however, was not satisfied (p=0.68). Efsitora was associated with a lower combined risk of clinically significant or severe hypoglycemia (0.50 events per participant-year of exposure) compared to glargine (0.88 events per participant-year of exposure) (estimated rate ratio 0.57, 95% CI 0.39-0.84). The efsitora group also received an overall lower insulin dose at week 52 (289.1U/week versus 332.8U/week in the glargine group) (EBGD -43.7U/week, 95% CI -62.4 to -25.0). Overall, 59.9% of patients in the efsitora group and 65.1% in the glargine group reported an adverse event. These results showed that among insulin-naïve patients with T2DM, basal weekly fixed-dose insulin efsitora was noninferior to daily insulin glargine in reducing HbA1c levels by 52 weeks of therapy.

Image: PD

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