Reducing injection burden has long been a priority in diabetes care. Now, a weekly, fixed-dose combination of basal insulin and a GLP-1 receptor agonist is one step closer to approval in Europe.

Kyinsu (insulin icodec with semaglutide; Novo Nordisk) received a positive recommendation from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use in September. The therapy is intended for adults with type 2 diabetes (T2D) mellitus whose glycemic control remains inadequate despite treatment with either basal insulin or a GLP-1 receptor agonist and is to be used alongside diet, physical activity, and oral antidiabetic drugs. 

T2D is a chronic metabolic disorder characterized by insulin resistance and progressive beta-cell dysfunction, resulting in hyperglycemia and subsequent multiorgan complications. Effective T2D management often requires therapies that target multiple glycemic pathways. 

Kyinsu combines two active agents with complementary mechanisms to enhance glycemic control. Insulin icodec, a basal insulin analogue, regulates glucose metabolism via insulin receptor activation, while semaglutide, a GLP-1 receptor agonist, modulates insulin and glucagon secretion in a glucose-dependent manner. 

Insulin icodec features three amino acid substitutions and a C20 eicosane fatty diacid chain enabling reversible albumin binding, which prolongs its half-life to approximately 196 hours, achieving steady state after 3-4 weekly doses. Each unit of icodec delivers the same glucose-lowering effect as one unit of standard daily basal insulins, with a once-weekly dose being seven times that of a daily basal insulin.

Evidence from the COMBINE-1, COMBINE-2, and COMBINE-3 trials has demonstrated that once-weekly Kyinsu significantly improved glycemic control in adults with T2D across various treatment backgrounds. 

In COMBINE-1, IcoSema (another name used in clinical trials for the combo) showed superior A1c reduction (-1.55%) compared with insulin icodec alone (-0.89%) and resulted in meaningful weight loss and lower hypoglycemia rates. COMBINE-2 demonstrated that IcoSema was also superior to semaglutide in reducing A1c (-1.35% vs -0.90%), though weight loss was greater with semaglutide alone. COMBINE-3 confirmed that IcoSema was noninferior to full basal-bolus insulin therapy for A1c reduction, while offering the additional benefits of significant weight loss and markedly lower rates of hypoglycemia. 

The most frequent adverse effects with Kyinsu include hypoglycemia, nausea, and diarrhea. 

If next approved by the European Commission, Kyinsu will be offered as a prefilled pen containing a fixed-dose combination of insulin icodec (700 U/mL) and semaglutide (2 mg/mL) for subcutaneous injection. Designed as a once-weekly therapy, it aims to simplify treatment and reduce the challenges of daily basal insulin, particularly injection burden and poor adherence.

Detailed recommendations for Kyinsu use will be described in the summary of product characteristics, which will be published on the EMA website once the European Commission grants marketing authorization.