In T2DM requiring insulin initiation, icodec titrated with an app safely reduced HbA1c vs. daily basal insulin analogues at 52 wk
An ACP Journal Club commentary cautioned that although a recent industry-funded trial was designed to approximate real-world practice, certain factors may still limit the generalizability of its findings.
A phase 3a study by Novo Nordisk randomized 1,085 insulin-naive adults with type 2 diabetes in seven countries to either weekly insulin icodec dosed by an app or a daily insulin analogue (insulin degludec, insulin glargine U100, or insulin glargine U300) dosed in a standard manner. It found that patients who used the weekly insulin with the app had greater reductions in HbA1c levels than those in the daily insulin groups.
The study was published by Annals of Internal Medicine on Sept. 26, 2023, and summarized in the October 2023 ACP Diabetes Monthly. The following commentary by Aris Liakos, MD, MSc, PhD, Thomas Karagiannis, MD, MSc, PhD, and Apostolos Tsapas, MD, PhD, MSc (Oxon), was published in the ACP Journal Club section of Annals on Jan. 2.
The industry-sponsored ONWARDS 5 trial by Bajaj and colleagues confirms that weekly icodec improved HbA1c more than daily basal insulins, without increasing risk for hypoglycemia in T2DM. This allays concerns about prolonged or recurrent hypoglycemia and slow recovery due to the extended elimination half-life of icodec. Results from a hypoglycemia induction study were already reassuring—even at double or triple doses, the onset and recovery times from hypoglycemia with icodec paralleled those observed with glargine U100 and were accompanied by equally robust counterregulatory responses to restore euglycemia.
The trial was designed to approximate routine clinical practice, with fewer trial visits, broader eligibility criteria, and flexibility in managing additional antidiabetes medications. However, various factors can limit the generalizability of its findings to a real-world clinical context. The trial involved highly motivated patients who were closely monitored by skilled health care professionals. A dose-guidance system composed of an app for participants and a portal for health care professionals was used to titrate insulin doses and may introduce a level of complexity and burden that could be impractical to implement. Even more, the dosing guide app was used exclusively in the icodec group, making it challenging to ascertain the net clinical benefits of icodec over daily basal insulins in the real-world setting.
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) outperform basal insulin for reducing HbA1c, weight control, and incidence of hypoglycemia and are thus recommended as first-line injectable therapy. Therefore, a comparison of icodec with optimized standard of care with GLP-1 RAs would be more clinically relevant. A co-formulation of icodec with the once-weekly GLP-1 RA semaglutide is currently being investigated in the COMBINE clinical development program (NCT05352815, NCT05259033, and NCT05013229) and has the potential to further simplify insulin therapy.