Once-Weekly Insulin: A Game-Changer for Primary Care

Presented at the European Association for the Study of Diabetes (EASD) 2024 congress in Madrid, the QWINT-2 study established that once-weekly dosing of insulin efsitora was as effective as once-daily dosing of insulin degludec for reducing A1c in patients with type 2 diabetes (T2D) who had not previously received insulin. Study participants were, however, receiving noninsulin glucose-lowering agents, including glucagon-like peptide 1 (GLP-1) receptor agonists. 
Slightly higher rates of mild to moderate hypoglycemia were noted with efsitora compared with degludec, but no significant differences in severe hypoglycemia were observed. Nor was there any difference in weight gain between groups, and adverse events were balanced between study arms. 
This study positions insulin efsitora alongside once-weekly insulin icodec as a novel long-acting insulin therapy. In the ONWARDS 3 trial, icodec was noninferior to once-daily degludec, in terms of A1c reduction. It also had an adverse effect profile like that of efsitora with respect to hypoglycemia and weight change.
So, what are the implications of a once-weekly insulin for primary care?
“Game-changer” is an overused term, but from the perspective of primary care, it applies to once-weekly insulin.
I initiate basal insulin much less frequently these days, given the multitude of noninsulin options now available to me in primary care, particularly the GLP-1 receptor agonists and the dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists. The American Diabetes Association/EASD 2022 consensus report also reminds me that GLP-1 receptor agonists should be considered in all individuals with T2D before insulin, unless they are contraindicated. GLP-1 receptor agonists are insulin-sparing agents with a lower injection burden and a lower risk for hypoglycemia. They also promote significant weight loss compared with basal insulin.
But progressive beta-cell decline and insulin deficiency are among the key pathophysiologic abnormalities in T2D. Eventually, many patients with T2D, despite lifestyle interventions and medication adherence, do require insulin. 
Understandably, many of my patients have reservations about commencing insulin. Significant stigma about starting insulin persists, because others often perceive insulin use as a failure to manage T2D. Patients frequently fear injections, and many are worried about how insulin therapy, specifically the risk for hypoglycemia, will affect their daily activities such as driving. 
Clinicians often experience therapeutic inertia, hesitating to escalate therapy to insulin because of a lack of confidence and competence, which often results from inadequate education. Lengthy referral-to-treatment waiting times are common in the United Kingdom, and there is concern about the workload implications associated with insulin initiation.
Workload is a particular concern for my community nursing colleagues, who must visit some of my more frail and functionally dependent patients daily to administer their insulin. 
In addition, the delivery of high-quality diabetes care in nursing homes, particularly for patients requiring insulin, has been a perennial challenge in the UK, again because of a lack of confidence and competence due to an absence of education for nursing and ancillary staff. 
Moreover, it is not appropriate to switch many of these frail patients to noninsulin therapies because of their insulinopenia, as well as the significant weight (and sometimes muscle) loss associated with GLP-1 receptor agonists. Also, sodium-glucose cotransporter 2 inhibitors are associated with a risk for volume depletion and diabetic ketoacidosis.
I believe that the availability of a once-weekly insulin will help overcome many of the above barriers.
From a patient’s viewpoint, simplification of insulin therapy with once-weekly insulin will substantially reduce the number of injections required (from 365 to 52 over 1 year). This change will improve compliance and concordance even in patients with injection anxiety. These results will hopefully translate into improved glycemic control and a lower risk for the complications of T2D. Real-world evidence for these outcomes is not yet available, however. Also, the reduced amount of insulin consumables that once-weekly dosing requires will also help improve the environmental footprint of insulin therapy.
From a clinician’s viewpoint, once-weekly insulin may seem less daunting and could reduce therapeutic inertia, thus facilitating earlier initiation of insulin therapy and reducing the risk for complications of T2D. Although education remains pivotal, this ease of dosing may be more acceptable to many clinicians because it has less of an effect on workload. This dosing could even save time because it requires less intensive follow-up than daily basal insulin does.
My community nurse colleagues were ecstatic when I mentioned that once-weekly basal insulin was on the horizon. This formulation could reduce the number of weekly home visits from 7 to just 1, thus freeing up considerable healthcare resources. And if once-weekly insulin is coupled with continuous glucose monitoring, then remote review of glucose data can further streamline and optimize the management of T2D in frail older patients. I am sure that my nursing-home colleagues will be equally enthusiastic about simplifying insulin regimens and monitoring.
Finally, an unanswered question is how I manage “sick days” for patients on weekly insulin dosing. Of course, the golden rule of never stopping insulin during intercurrent illness must be followed, but is any dose titration required for once-weekly insulin? I suspect not, but do I need to consider adding a once-daily basal insulin or rapid-acting insulin to mitigate the glucose counterregulatory hormone response during acute illness? Initially, I will be asking specialist diabetes teams for further advice on managing sick days.
In conclusion, once-weekly dosing of insulin is a game-changer for primary care and could finally be the driver to quash therapeutic inertia and address common patient barriers when escalation to insulin is required.