Once-Weekly Insulin Icodec, Semaglutide Regimen Reduced HbA1c in Patients With Type 2 Diabetes

Results from the phase 3a trial COMBINE 3 demonstrate the efficacy and safety of once-weekly fixed-ratio combination of basal insulin icodec and semaglutide (IcoSema; Novo Nordisk) compared to once-daily insulin glargine U100 and insulin aspart, dosed with or without oral glucose-lowering medications. The trial reached its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 52.

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The combination regimen consists of once-weekly basal insulin icodec and once-weekly semaglutide (700U/2 mg/mL) and has a maximum weekly dose of 350 dose steps (e.g., 350 U insulin icodec/1 mg semaglutide). The 52-week, open-label treat-to-target trial enrolled a total of 679 patients with type 2 diabetes who were inadequately controlled on daily basal insulin to compare the efficacy and safety of once-weekly basal insulin icodec and semaglutide with once-daily insulin glargine U100 and insulin aspart (injected 2 to 4 times per day at mealtimes).

The trial results demonstrate that basal insulin icodec with semaglutide was more effective than insulin U100 and insulin aspart in estimated rates of severe or clinically significant hypoglycemia (0.26 events per patient-year of exposure vs. 2.18 events per patient-year of exposure, respectively). In addition, once-weekly basal insulin icodec with semaglutide achieved an estimated reduction in HbA1c of -1.47%, unlike insulin glargine U100 and insulin aspart, which reached a reduction of -1.40% (from an overall baseline of 8.30%). In addition, those treated with basal insulin icodec with semaglutide with a baseline body weight of 85.8 kg experienced a reduction of weight loss (-3.6 kg), unlike those treated with insulin glargine U100 and insulin aspart, who gained weight (3.2 kg).

Further, the once-weekly basal insulin icodec with semaglutide regimen had demonstrated a safe and well-tolerated profile. The most common adverse events reported by patients who were treated with this combination treatment were mild to moderate in severity and were gastrointestinal, consistent with the GLP-1 receptor agonist class.

“We are very pleased to share the first phase 3a results for once-weekly [basal insulin icodec with semaglutide],” said Martin Holst Lange, executive vice president for development at Novo Nordisk, in a press release. “The results demonstrate the potential of [this regimen] to simplify insulin intensification by reducing the injection burden to a single injection per week compared to around 28 injections per week for people with type 2 diabetes inadequately controlled on basal insulin while providing glycemic control as well as weight benefits and lower rates of hypoglycemia.”

Reference

Novo Nordisk. COMBINE 3 phase 3a trial successfully completed with once-weekly IcoSema demonstrating non-inferior reduction in HbA1c versus daily basal-bolus treatment (insulin glargine U100 and insulin aspart) in people with type 2 diabetes. News release. January 8, 2024. Accessed January 10, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=167008