Weekly insulin efsitora alfa demonstrates noninferiority to daily degludec in type 2 diabetes

medwireNews: Once weekly treatment with insulin efsitora alfa reduces glycated hemoglobin (HbA1c) by a similar amount to daily treatment with insulin degludec in people with type 2 diabetes who have not previously received insulin, results of the QWINT-2 trial show. “Tight glycemic control was achieved with overall low rates of hypoglycemia,” write Carol Wysham (MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, Washington, USA) and co-authors in The New England Journal of Medicine. They explain that efsitora is a new basal insulin designed to have a flat pharmacokinetic profile and long half-life, allowing for once-weekly administration. So far, safety and efficacy data have been limited to small, phase 1 or phase 2 trials. The current phase 3, treat-to-target trial, which was simultaneously presented at EASD 2024 in Madrid, Spain, included 928 adults (59% men, mean age 57 years) with type 2 diabetes (mean duration 12 years) who had not previously received insulin. They were randomly assigned to receive once weekly efsitora (100 units/week; n=466) or once-daily degludec (10 units/day; n=462), both in combination with noninsulin glucose-lowering agents, for 52 weeks. Participants in the efsitora group received a one-time starting dose of 300 units, to allow efsitora to reach efficacious concentrations. In both treatment groups, dose assessments and adjustments aimed at achieving a target of 80–120 mg/dL (4.4–6.6 mmol/L) were carried out weekly up to week 12 and at least every 4 weeks thereafter. The researchers report that mean HbA1c levels decreased from 8.21% (66 mmol/mol) at baseline to 6.97% (53 mmol/mol) at week 52 with efsitora and from 8.24% (67 mmol/mol) to 7.05% (54 mmol/mol) with degludec. The reduction in HbA1c was a nonsignificant 0.09 percentage points greater with efsitora than with degludec, which was within the 0.40 percentage point margin for noninferiority. Wysham and team note that the results were similar regardless of glucagon-like peptide-1 receptor agonist use and that, irrespective of insulin type, a mean HbA1c level below 7.0% (53 mmol/mol) was reached by week 16 and sustained until the end of the study in both groups. Between weeks 48 and 52, participants given efsitora spent 64.3% of time within the glucose target range of 70–180 mg/dL (3.9–10.0 mmol/L), while those given degludec were within target range 61.2% of time. The resulting nonsignificant estimated treatment difference of 3.1 percentage points corresponds to an equivalent of 44 additional minutes per day in which the glucose level was within the target range among participants using efsitora, the researchers say. The investigators also found that the rate of combined clinically significant or severe hypoglycemia was similar between the two treatment arms at 0.58 and 0.54 events per participant–year of exposure with efsitora and degludec, respectively. However, the were no cases of severe hypoglycemia among people given efsitora and six episodes among those using degludec. Wysham et al point out that five of these six participants were using sulfonylureas, and all had a baseline estimated glomerular filtration rate above 60 mL/min per 1.73 m2. Serious adverse events occurred in 8.8% of people in the efsitora arm and 8.2% of those in the degludec arm. There were no treatment-related deaths in either group. Wysham et al conclude: “A once-weekly insulin has the potential to simplify dose administration and diminish barriers to starting insulin therapy by means of a reduction in injection burden as compared with a once-daily insulin.” medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group N Engl J Med 2024; doi:10.1056/NEJMoa2403953 EASD 2024; Madrid, Spain: 9–13 September

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Weekly insulin efsitora alfa demonstrates noninferiority to daily degludec in type 2 diabetes

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