Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial
Insulin efsitora alfa (efsitora) is a once-weekly basal insulin.
This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes.
In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA1c reduction compared with daily insulin degludec.
Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes.
Effective insulin treatment of type 1 diabetes requires multiple daily injections of basal and bolus insulin or the use of continuous subcutaneous insulin infusion.
Basal insulin options require once or twice daily injections.
Reducing the frequency of basal insulin injections has the potential to simplify treatment and ease the burden on people with diabetes and their caregivers, which could ultimately improve adherence and glycaemic outcomes.
With the development of once-weekly basal insulins, a decrease in the number of basal insulin injections from about 365 to 52 per year could reduce this burden.
Insulin efsitora alfa, is a fusion protein combining a single-chain variant of insulin with a human IgG Fc domain.
It is an insulin receptor agonist designed to have a flat pharmacokinetic profile and long half-life, which allows for weekly dosing.
Findings from a phase 2, 26-week trial in adults with type 1 diabetes showed the efficacy of efsitora, as measured by HbA1c, to be non-inferior to insulin degludec with a statistically significant treatment difference favoring degludec.
In the phase 2 study, fasting glucose levels were higher with efsitora, and the rates of level 2 hypoglycemia (<54 mg/dL [3·0 mmol/L]) and nocturnal hypoglycaemia were comparable between treatments.
Another weekly basal insulin, icodec, has been evaluated in adults with type 1 diabetes and has shown non-inferiority in HbA1c reduction and increased level 2 and level 3 hypoglycemia compared with degludec.
A preclinical study and a phase 1 trial reported that the half-life of efsitora is 17 days with a 1·14 peak-to-trough insulin ratio over the course of the week.
Phase 2 trials in people with type 1 diabetes or people with type 2 diabetes, insulin naive and those previously treated with basal insulin, showed comparable glycemic control, as measured by glycated haemoglobin A1c (HbA1c), between efsitora and insulin degludec.
In people who were insulin naive with type 2 diabetes or type 1 diabetes, the rate of hypoglycemia was similar for efsitora and degludec.
A lower rate of hypoglycaemia was shown in people with type 2 diabetes previously treated with basal insulin with efsitora compared with degludec.
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