Top 10 Global Diabetes Drugs in 2018 and Market Trends

In 2018, the combined sales revenue of the top 10 global antidiabetic drugs reached $28.5 billion, dominated by insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Metformin, widely used in clinical practice, was excluded from the list due to its low price following patent expiration. Meanwhile, the emerging sodium-glucose cotransporter-2 (SGLT2) inhibitors are poised to enter the list next year, driven by their rapid growth trajectory.

As the primary class of medications for diabetes, insulin products are facing internal and external market pressures as multiple patents expire. With the rapid development of biosimilar technology, these products are encountering competition from other categories, leading to a gradual erosion of market share for several blockbuster drugs. For instance, Sanofi’s insulin glargine, and Novo Nordisk’s insulin aspart, insulin detemir, and human insulin have all experienced declines in market performance.

Faced with the aggressive rise of GLP-1 receptor agonists and SGLT2 inhibitors, insulin tearfully laments: "The new waves of the Yangtze River drive on those before; each generation outshines the last!"

Currently, the most striking development in the diabetes market is the rapid growth of GLP-1 receptor agonists, marked by the intense rivalry and competitive interplay between Novo Nordisk and Eli Lilly.

Advantages of GLP-1 Receptor Agonists: In addition to lowering blood glucose, they provide additional cardiovascular benefits, reduce food intake, and delay gastric emptying, thereby facilitating weight control (as weight-loss medications). Furthermore, the incidence of hypoglycemic events is significantly lower than that associated with insulin.

The half-life of endogenous GLP-1 in the human body is very short. Although early modified GLP-1 receptor agonists showed some improvement in half-life, their dosing intervals remained short, and their clinical advantages in glycemic control were not sufficiently significant. With the market launch of Novo Nordisk’s liraglutide and Eli Lilly’s long-acting GLP-1 receptor agonist dulaglutide in 2014, GLP-1 receptor agonists experienced rapid growth.

Liraglutide has replaced insulin aspart as Novo Nordisk’s flagship product, generating $4.63 billion in sales in 2018 and becoming a bona fide blockbuster drug. Eli Lilly’s dulaglutide is equally formidable, maintaining rapid annual growth and poised to surpass liraglutide’s leading position within two years.

Certainly, Novo Nordisk, the reigning "king of diabetes," will not easily cede its throne to Eli Lilly. Semaglutide, launched in December 2017, outperformed dulaglutide in head-to-head comparisons for both glycemic control and weight loss, becoming the most effective diabetes medication to date. With future approvals expected for indications in weight management and cardiovascular disease, semaglutide is poised to become Novo Nordisk’s primary growth driver.

To further consolidate its dominant market position, Novo Nordisk addressed the management of diabetes as a chronic condition by launching an oral formulation of semaglutide, which significantly improved patient adherence. Its large-scale PIONEER 1–10 clinical trial program successively demonstrated superiority over empagliflozin (the best-selling SGLT2 inhibitor) and sitagliptin (the best-selling DPP-4 inhibitor), and showed efficacy comparable to liraglutide (the best-selling GLP-1 receptor agonist). The trials revealed superior glycemic control and weight loss effects compared with existing marketed agents. Additionally, the drug provided clinical benefits to patients with moderate renal impairment and delivered significant clinical benefits to patients with type 2 diabetes receiving basal insulin therapy. On March 20, 2019, Novo Nordisk submitted two marketing applications to the FDA for oral semaglutide: one as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and the other to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes and established cardiovascular disease.

As the storm approaches, the wind fills the tower; Novo Nordisk’s semaglutide will undoubtedly lead the trend in glucose-lowering medications.

As the leading chronic disease in terms of management scale, the heavy economic burden of long-term medication for patients is a key factor driving volume growth in China. Due to their significantly higher prices compared to insulin, metformin, and sulfonylureas, GLP-1 receptor agonists, which have seen smooth sailing globally, have not achieved expected success in the Chinese market. In July 2017, Novo Nordisk’s liraglutide was included in Category B of the National Reimbursement Drug List (NRDL) through national reimbursement negotiations, with a reimbursed price of RMB 410 per pen, making it the only GLP-1 receptor agonist currently covered by medical insurance in China, thereby facilitating market expansion. In February 2019, Eli Lilly’s dulaglutide was approved for launch in China, and Hansoh Pharmaceutical’s first domestically produced long-acting GLP-1 receptor agonist, pegylated exenatide (polyethylene glycol-loxenatide), is also imminent. The Chinese diabetes market is poised for a new round of intense competition, with subsequent NRDL negotiations, price fluctuations, and undercurrents in the market undoubtedly becoming the focal points of the diabetes sector.

DPP-4 inhibitors are also facing a dilemma similar to that of insulin, struggling to balance competing priorities; under the impact of generic drugs and intense competition from GLP-1 receptor agonists, they no longer enjoy their former glory.

Since its FDA approval in 2012, SGLT-2 inhibitors have become a major trend in diabetes drug development in recent years, with the market showing an overall upward trajectory. The most notable products are AstraZeneca’s dapagliflozin and empagliflozin, jointly developed by Eli Lilly and Boehringer Ingelheim. Among these, empagliflozin is currently the only oral hypoglycemic agent proven to have significant efficacy in glycemic control, cardioprotection, renal protection, and weight reduction. Highly anticipated by the industry, it is expected to achieve $3.5 billion in sales in 2024, securing its place among the top three antidiabetic drugs.

Company Ranking:

Novo Nordisk, growing stronger with age, has capitalized on the surge in GLP-1 receptor agonists and its extensive insulin pipeline to secure the top-selling diabetes medication and widen its lead over competitors, basking in remarkable success.

Eli Lilly, buoyed by the skyrocketing growth of its once-weekly long-acting GLP-1 receptor agonist dulaglutide, is brimming with confidence and poised to challenge Novo Nordisk.

Boehringer Ingelheim, a rising star in the diabetes market, has seen its sales soar with the launch of empagliflozin and is poised to surpass Sanofi to break into the top three in the coming years.

Sanofi has relinquished its No. 1 position in diabetes care due to the patent expiration of its flagship product, insulin glargine. In R&D, Soliqua (insulin + GLP-1), a blockbuster drug held in high expectation, has shown year-over-year performance that pales in comparison to Novo Nordisk’s semaglutide. The company’s traditional stronghold has declined from its former prominence amid repeated setbacks.

Merck, basking in the glory of tumor immunotherapy, seems too preoccupied to address the patent expiration of its flagship diabetes drug, sitagliptin. With no standout products in its R&D pipeline to follow up, the company appears to have adopted a laissez-faire attitude: “As long as you’re happy!”

Source: Pharmadl Author: Si Tie