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A once-weekly injection of insulin is as effective as daily injections for blood sugar management in both type 1 and type 2 diabetes mellitus (T1DM/T2DM), studies have suggested.
In a phase 3, non-inferior study, published in The Lancet on 10 September 2024, 692 adults with T1DM were randomly assigned to receive either once-weekly insulin efsitora (n=343) or once-daily insulin degludec (n=349), both in combination with insulin lispro.
The study aimed to assess the efficacy and safety of efsitora compared with degludec by measuring the change in glycated haemoglobin (HbA1c) and incidence of severe hypoglycaemia during the 52-week study period.
At week 26, researchers found that mean HbA1c decreased from 7.88% (62.66 mmol/mol) at baseline to 7.41% (57.5 mmol/mol) with efsitora, compared with 7.94% (63.3 mmol/mol) at baseline to 7.36% (56.9 mmol/mol) with degludec — a mean change of -0.51% with efsitora and -0.56% with degludec — confirming a non-inferiority margin of 0.4% for efsitora compared with degludec.
However, the incidence rate of moderate or severe hypoglycaemia with efsitora compared with degludec was 14.03 versus 11.59 events per patient-year of exposure — an increased risk of 21%, which was statistically significant.
The incidence of severe hypoglycaemia was also reported more frequently in the efsitora cohort at 10% (n=35/343), compared with degludec at 3% (n=11/349), during the 52-week period. Hypoglycaemia was reported more frequently in the first 12 weeks of the trial.
The authors noted that while efsitora showed non-inferior HbA1c reduction compared with degludec, the greater incidence of severe hypoglycaemia in participants treated with efsitora may “suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes”.
Another phase 3, non-inferior study, published on 10 September 2024 in the New England Journal of Medicine, included 928 participants with T2DM, who were randomly assigned to receive either efsitora (n=466) or degludec (n=462) over 52 weeks.
At week 52, researchers found that mean HbA1c decreased from 8.21% at baseline to 6.97% with efsitora (−1.26 percentage points) and from 8.24% to 7.05% with degludec (−1.17 percentage points), with an estimated treatment difference of −0.09 percentage points, demonstrating non-inferiority of the weekly injection.
The T2DM study also observed an incidence rate of moderate or severe hypoglycaemia with efsitora compared with degludec at 0.58 versus 0.45 events per participant-year of exposure; however, these findings were not statistically significant.
Commenting on the studies, Philip Newland-Jones, consultant pharmacist in diabetes and endocrinology at University Hospital Southampton NHS Foundation Trust, said: “Once-weekly insulin has the potential to support in those patients who have insulin resistance in T2DM and require similar background doses of insulin daily.
“There are possible groups that may benefit from once-weekly dosing, such as those requiring district nurses; however, there are also potential risks to take into consideration in this group,” he added.
“I believe that in line with data for insulin icodec once-weekly insulin, these data confirm that these insulins are unlikely to be used widely in T2DM because of the increased risk of hypoglcyaemic episodes compared with standard care.
“This is likely to be due to the differing daily requirements and flexibility in insulin required in the management of T1DM, further highlighting the benefits of hybrid closed-loop insulin systems, which can vary background insulin requirements,” explained Newland-Jones.
Similar to insulin efsitora, insulin icodec is a once-weekly injection, which is currently under review for regulatory approval for treatment of T2DM. However, it has also been associated with an increased risk of hypoglycaemia.
Guidance from the National Institute for Health and Care Excellence on icodec is expected to be published in May 2025.
Also commenting on the studies, Katie Bareford, senior clinical advisor at Diabetes UK, said: “Keeping blood sugars in target range with insulin therapy can be relentless and exhausting.
“A reduction in the number of insulin injections could lessen the burden of living with diabetes and better support people in their efforts to manage their diabetes.
“We welcome these findings and look forward to further research on once-weekly insulin injections to ensure they are safe and effective for everyone who could benefit,” she said.
