In uncontrolled T2DM treated with a basal-bolus insulin regimen, weekly icodec was noninferior to daily glargine for HbA1c at 26 wk

A recent industry-funded trial compared insulin icodec, a once-weekly basal insulin currently under development, to insulin degludec in patients with type 2 diabetes. It found that the average HbA1c level of the patients who started weekly icodec dropped from 8.17% to 7.20%, compared to 8.10% and 7.42%, respectively, in patients on daily degludec.

The study was published by The Lancet Diabetes & Endocrinology on May 5 and summarized in the May ACP Diabetes Monthly. The following commentary by Heiba Belal, MD, and Gunjan Y. Gandhi, MD, MSc, was published in the ACP Journal Club section of Annals of Internal Medicine on Aug. 1.

Complex diabetes treatment regimens with multiple insulin injections, hypoglycemia risk, and weight gain lead to treatment dissatisfaction and inertia among providers to intensify therapy, which can hinder achieving sustained and effective glycemic goals. The advent of newer insulins such as icodec that are suitable for once-weekly dosing could provide greater flexibility in insulin administration, mimic normal physiology, and reduce treatment burden.

Mathieu and colleagues found that in patients treated with a basal-bolus regimen, once-weekly icodec was noninferior to once-daily glargine, with no difference in significant or severe hypoglycemia. Once-weekly icodec may increase risk for mild hypoglycemia—a particular concern for older adults and patients with an increased risk for falls. The hypoglycemic risk in response to unplanned exercise or during illnesses requiring hospitalization is unclear, and hypoglycemic events could be protracted. The use of ultra-long-acting insulin in patients with obesity, renal failure, liver failure, and those with type 1 diabetes (who often have greater insulin sensitivity and lower hypoglycemia awareness) needs further assessment.

The real-life benefit of weekly icodec may be optimal in persons with type 2 diabetes treated with oral agents or weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) who need additional basal insulin. The number of injections would be reduced to 52 from 365/y vs. once-daily basal insulins. The growing popularity of a once-weekly injectable GLP-1 RA makes adding once-weekly basal insulin such as icodec attractive: It could enhance treatment adherence and possible cardiovascular benefit while negating the harmful effects of weight gain and hypoglycemia risk. The advantage of fewer insulin injections may well be less for those treated with a basal-bolus regimen as they still need to administer bolus injections several times per day. Ongoing clinical trials are evaluating the safety and efficacy of another novel once-weekly Efsitora Alfa insulin compared with once-daily basal insulin.