TOPLINE:
Once-weekly IcoSema — a combination of basal insulin icodec and the GLP-1 receptor agonist semaglutide — achieved a noninferior reduction in A1c levels compared with daily basal-bolus therapy in patients with type 2 diabetes (T2D) inadequately controlled with daily basal insulin. The treatment also led to greater body weight reduction, lower weekly insulin dose requirements, and fewer hypoglycemic episodes.
METHODOLOGY:
- An unmet need exists for therapies that reduce injection burden while effectively controlling glucose levels, managing weight, and minimizing hypoglycemia risk.
- Researchers conducted a phase 3 trial (COMBINE 3) to evaluate the efficacy and safety of IcoSema vs basal-bolus therapy in adults with T2D inadequately controlled with daily basal insulin.
- A total of 679 patients (mean age, 59.6 years; 41% women; mean A1c levels, 8.3%) receiving daily basal insulin (20-80 U) were randomly assigned to receive either once-weekly IcoSema or once-daily basal-bolus therapy.
- The IcoSema group received the treatment once weekly via a pen device at a starting dose of 40 dose steps (equivalent to 40 U icodec and 0.114 mg semaglutide), while the basal-bolus group received once-daily insulin glargine U100 along with two to four daily injections of insulin aspart.
- The primary endpoint was the change in A1c levels from baseline to week 52, with a noninferiority margin of 0.3 percentage points; secondary endpoints included changes in body weight, episodes of clinically significant hypoglycemia through week 57, and a weekly total insulin dose during weeks 50-52.
TAKEAWAY:
- At week 52, IcoSema was noninferior to basal-bolus therapy (estimated mean change in A1c levels, -1.47 vs -1.40 percentage points; estimated treatment difference [ETD], -0.06 percentage points; P for noninferiority < .0001).
- From baseline to week 52, mean body weight decreased by 3.56 kg with IcoSema but increased by 3.16 kg with basal-bolus therapy (ETD, -6.72 kg; P < .0001).
- IcoSema vs basal-bolus therapy also led to lower weekly total insulin doses (ETD, -270 U; P < .0001) and fewer clinically significant hypoglycemia episodes (0.21 vs 2.23 episodes per person-year of exposure; P < .0001).
- Serious adverse events were reported in 13% of patients receiving IcoSema vs 9% of those receiving basal-bolus therapy; gastrointestinal disorders were the most frequent adverse events with IcoSema.
IN PRACTICE:
“Once-weekly IcoSema achieved noninferior A1c reduction and superiority in change in bodyweight, weekly total insulin dose, and hypoglycemia rates vs daily BBT [basal-bolus therapy], suggesting that there is a potentially beneficial treatment intensification option for adults with type 2 diabetes,” the authors concluded.
SOURCE:
This study was led by Liana K. Billings, MD, Endeavor Health/NorthShore Hospitals and the University of Chicago Pritzker School of Medicine, Chicago. It was published online in The Lancet Diabetes & Endocrinology.
LIMITATIONS:
This study was limited by its open-label design and the absence of information on adherence.
DISCLOSURES:
The study was funded by Novo Nordisk. Some authors reported receiving research support or consultant fees, serving on advisory panels, or having other ties with various pharmaceutical and healthcare companies, including the funding agency. Three authors reported being employees of Novo Nordisk and holding stock options.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.