New research published in The Lancet and presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Madrid (9-13 Sept) shows that a new class of insulin that only needs to be injected once weekly is as effective as daily insulin injections for effective blood sugar management in patients with type 1 diabetes. However, higher rates of hypoglycaemia using the new class means vigilance is needed for dose initiation and optimisation. The study is by Dr Richard M Bergenstal, International Diabetes Center, HealthPartners Institute, Minneapolis, MN, USA, and colleagues.
The previous phase 2 study of weekly insulin efsitora alfa in people with type 1 diabetes showed non-inferior glycated haemoglobin (HbA1c) (a measure of blood sugar control) reduction compared with daily insulin degludec without increased combined level 2 (<54 mg/dl [3.0 mmol/l) or level 3 hypoglycaemia over 26 weeks of treatment, but with statistically significantly higher glycated haemoglobin and fasting glucose than degludec.
Thus, in this new phase 3 study, a new dosing approach was implemented in the QWINT-5 study based on the phase 2 results to balance glycaemic efficacy with hypoglycaemia risk. This randomised 52-week study conducted at 82 global health-care centres, randomly assigned (1:1) adults aged over 18 years with type 1 diabetes glycated haemoglobin 7.0 - 10.0% (53.0-85.8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. Insulin lispro was used to have a consistent 'meal time' insulin in both groups, so that the only insulin difference in the two treatment arms was the type of background or 'basal' insulin. The primary endpoint was the change in HbA1c from baseline to week-26 (noninferiority margin=0.4%).
Between Aug 12, 2022, and May 7, 2024, 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA1cdecreased from 7.88% (62.66 mmol/mol) at baseline to 7.41% (57.5 mmol/mol) at week 26 with efsitora and from 7.94% (63.3 mmol/mol) at baseline to 7.36% (56.9 mmol/mol) at week 26 with degludec. Mean HbA1c change from baseline to week 26 was -0.51% with efsitora and -0.56% with degludec (estimated treatment difference 0.052%) confirming a non-inferiority margin of 0.4% for efsitora compared with degludec.
Rates of combined level 2 (<54 mg/dL [3.0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14.03 vs 11.59 events per patient year of exposure; an increased risk of 21% (statistically significant) for patients receiving efsitora during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group.
Dr Bergenstal concludes: "Our study showed that once-weekly efsitora improved HbA1c in people with type 1 diabetes with similar HbA1c reduction to degludec. More work is needed to evaluate efsitora dose initiation and optimisation of basal-bolus insulin dosing to maintain efficacy while mitigating the risk of hypoglycaemia with weekly efsitora treatment in people with type 1 diabetes."
