Novo Nordisk Launches China's First Soluble Co-Formulated Insulin, NovoMix® (Insulin Degludec/Insulin Aspart), for Adults with Type 2 Diabetes

On November 28, Novo Nordisk’s diabetes drug liraglutide injection successfully renewed its contract and was once again included in the National Reimbursement Drug List through negotiated access. Less than ten days later, on December 7, another innovative diabetes medication from Novo Nordisk, insulin degludec/insulin aspart injection (NovoMix®), was officially launched in China for the treatment of type 2 diabetes in adults. This is the world’s first dual-insulin formulation approved for diabetes treatment. To date, NovoMix® has been marketed in 29 countries and regions globally.

The "Uniqueness" of Chinese Patients with Diabetes

It is well known that China has become a country with a high burden of diabetes. According to data from the International Diabetes Federation (IDF), the prevalence of diabetes in China is as high as 10.9%, with more than 121 million affected individuals, ranking first globally. However, in contrast, on one hand, the rate of glycemic control among Chinese patients with diabetes is only 15.8%, and poor glycemic control is the main reason for the high incidence of complications in these patients. On the other hand, as type 2 diabetes progresses, patients require exogenous insulin therapy; however, the initiation of insulin therapy in China is generally delayed, and the proportion of insulin use is relatively low, which is not conducive to preserving β-cell function and improving endogenous insulin secretion.

Professor Mu Yiming, Director of the Department of Endocrinology at the Chinese PLA General Hospital, stated: “Insulin remains one of the most effective treatments for diabetes. However, in addition to the relatively low utilization rate of insulin among diabetic patients in China, there are still many unmet clinical needs in current insulin therapy regimens. For instance, existing insulin regimens fail to adequately mimic the physiological pattern of insulin secretion and cannot reduce the risk of hypoglycemia while simultaneously managing both fasting and postprandial blood glucose levels. Furthermore, some patients experience poor glycemic control during insulin therapy, characterized by fluctuating blood glucose levels and nocturnal hypoglycemia.”

Professor Ji Linong, Director of the Department of Endocrinology at Peking University People’s Hospital, also pointed out: “Hypoglycemia is an inevitable side effect of insulin therapy. The closer glycemic control approaches the target level during insulin treatment, the higher the risk of hypoglycemia. Consequently, patients’ fear of hypoglycemia becomes a barrier to high-quality diabetes management, leading them to arbitrarily reduce their medication dosage or engage in preventive eating, which is detrimental to long-term glycemic control.”

It is understood that, in clinical practice, hypoglycemic events can range from mild symptoms such as dizziness to severe manifestations including confusion and altered mental status, and may even lead to death in some cases. A patient survey on hypoglycemia risk conducted by the International Diabetes Federation (IDF) in collaboration with Novo Nordisk revealed that hypoglycemia currently represents a major treatment challenge for diabetes patients worldwide. 46.5% of patients with type 2 diabetes mellitus (T2DM) experienced one or more episodes of hypoglycemia within an average month⁴. 21% of patients receiving insulin therapy expressed concern about the risk of hypoglycemia, and as many as 36.7% of T2DM patients reduced their insulin dosage due to fears of hypoglycemia.

It is also worth noting that the dietary habits of Chinese patients with diabetes determine their individualized needs for insulin therapy. As refined rice and wheat products, which have a high glycemic index, constitute the staple food for all three meals among Chinese patients, they exert a significant impact on postprandial blood glucose levels. Furthermore, due to differences in genetic factors and other variables, even when consuming equal amounts of the same type of grain, Chinese individuals experience a greater impact on blood glucose levels than Europeans.

Therefore, both Professor Mu Yiming and Professor Ji Linong stated that, considering dietary habits and the characteristics of blood glucose fluctuations, patients with diabetes in China urgently need an insulin therapy regimen that can simultaneously cover both fasting and postprandial blood glucose levels.

The launch of Ryzodeg® will bring a new personalized solution for Chinese patients with diabetes to achieve comprehensive glycemic control targets.

Precise “70% Insulin Degludec + 30% Insulin Aspart”

As the first soluble dual-insulin formulation, Ryzodeg® consists of 70% insulin degludec and 30% insulin aspart, effectively addressing both fasting and postprandial blood glucose control.

Regarding the 70%+30% ratio, Zhang Kezhou, Corporate Vice President of the Pharmaceutical Quality Department at Novo Nordisk Greater China, stated toMedValleyThe reporter stated, “The 70:30 ratio of insulin degludec to insulin aspart in NovoMix® is derived from Novo Nordisk’s nearly century-long experience in insulin research and development. The 70% insulin degludec component meets the 24-hour basal insulin control needs, while the 30% prandial insulin component effectively controls postprandial blood glucose after main meals. The two components do not interfere with each other structurally and act independently, leveraging the long-acting, stable, peak-free glucose-lowering advantage of insulin degludec and the rapid glucose-lowering effect of insulin aspart. This combination addresses both fasting and postprandial blood glucose control, achieving complementary benefits. Therefore, the combination of 70% insulin degludec and 30% insulin aspart represents the optimal ratio.”

Professor Ke Zhousi, Chief Scientific Advisor for R&D and Lead Scientist of the Insulin R&D Team at Novo Nordisk, further pointed out in interviews with media outlets, including Yigu, that during Phase II clinical trials, Novo Nordisk had indeed tested a 55:45 ratio. However, this formulation failed to adequately mimic the physiological secretion profile of endogenous insulin. Consequently, the final formulation adopted a 70:30 ratio.

“Premixed insulin has a drawback known as the ‘shoulder effect,’ which refers to the overlap between its basal and prandial components. NovoRapid® overcomes the varying limitations of existing treatment regimens. Upon subcutaneous injection, insulin degludec forms long chains of multi-hexamers, providing continuous 24-hour coverage and stable control of fasting blood glucose; insulin aspart rapidly dissociates into monomers, quickly lowering postprandial blood glucose. These two bioactive substances are combined in a fixed ratio as a clear solution, maintaining their respective pharmacokinetic profiles in vivo. This effectively avoids the ‘shoulder effect,’ helping patients reduce the risk of hypoglycemia, decrease the frequency of injections, and alleviate psychological burden,” added Professor Ke Zhousi.

The results of the Phase 3 registration trial in Japan (Onishi study) demonstrated that, compared with insulin glargine, once-daily pre-prandial injection of insulin degludec/insulin aspart provided superior control of HbA1c and postprandial blood glucose over a 26-week treatment period. The risk of confirmed hypoglycemia was reduced by 27%, and the risk of nocturnal confirmed hypoglycemia was reduced by 25%, thereby ensuring safety while achieving effective glycemic control.

Notably, compared with the traditional intensive regimen of basal-bolus therapy involving 2–4 daily injections, Ryzodeg® requires fewer injections while achieving similar glycemic control and significantly reducing the risk of confirmed nocturnal hypoglycemia. It does not require resuspension before use, and a single insulin injection pen provides dual glycemic control for both fasting and postprandial blood glucose. Furthermore, as a next-generation insulin analog, Ryzodeg® is paired with Novo Nordisk’s latest generation of prefilled injection pens—the FlexTouch® pen—further enhancing convenience for patients.

“NovoMix® effectively addresses the primary demand of patients in China for convenience in treatment regimens; more importantly, from a physician’s perspective, NovoMix® meets our requirements for the efficacy and safety of treatment options,” stated Professor Mu Yiming.

Professor Ji Linong also pointed out: “Clinical development studies for NovoJia® involved 39 countries, including China, and nearly 1,000 research centers worldwide. The accumulated clinical evidence from these studies demonstrates that, whether used as initial therapy or as intensified treatment, NovoJia® achieves effective glycemic control with a lower risk of hypoglycemia compared to other insulin therapies, thereby enhancing the safety of insulin treatment.”

Striving toIntroduction of More Innovative Drugs, Including Semaglutide, into China

As a globally recognized leader in diabetes care and the world’s largest insulin manufacturer, Novo Nordisk has always placed great emphasis on its development in the Chinese market. To date, multiple Novo Nordisk products have been introduced into China. According to Zhou Xiaping, Senior Vice President of Novo Nordisk Global and President of Greater China, in an interview with Yigu reporters: “In the Chinese market, Novo Nordisk offers a comprehensive portfolio of diabetes products. Currently, we have launched 15 innovative products and 8 injection devices in China. We will continue to adopt a patient-centric approach, lead innovative breakthroughs in the field of diabetes, accelerate the introduction of innovative drugs, provide robust treatment solutions for Chinese physicians and patients, promote the simultaneous approval of new drugs in China and globally, and ensure that patients in China benefit from innovative achievements at the same time as patients worldwide. We will also continuously improve drug accessibility to benefit more patients in China.”

According to Zhou Xiaping, who revealed to a reporter from Yigu that Novo Nordisk is also intensively preparing to introduce another blockbuster diabetes drug, the once-weekly injectable semaglutide (Ozempic), into China. Meanwhile, the Phase III registration clinical trials for oral semaglutide (Rybelsus, taken once daily) have also been initiated.

Ozempic was first approved by the FDA in late 2017, and its global sales revenue reached $563 million in the first half of 2019, with annual sales expected to exceed $1 billion, making it a blockbuster drug. Rybelsus received FDA approval this September, with approved therapeutic doses of 7 mg and 14 mg. As the first oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the FDA, its emergence has broken the paradigm wherein patients with type 2 diabetes required daily or weekly GLP-1 RA injections, providing them with a less invasive and more convenient treatment option for glycemic control.