New drug development, fierce competition among leading companies in the diabetes drug market

Due to the change of life>
.
Whether diabetes can have cardiovascular benefits in single drug or drug combination therapy requires a large amount of clinical trial data to prove it.
This makes small companies rarely try to enter the diabetes treatment drug market alone, while giant companies are committed to exploring more diabetes treatment drugs.
Many indications
.

  Eli Lilly and Novo Nordisk's GLP-1 drug battle

  The main competitors in the field of glucagon-like peptide-1 (GLP-1) receptor agonists are Eli Lilly and Novo Nordisk
.

  In 2014, Eli Lilly's dulaglutide went on the market, and in just 6 years it became a blockbuster drug with sales of up to $5 billion, and it became the champion of GLP-1 drug sales (see figure)
.
In 2009, Novo Nordisk’s liraglutide was launched.
The drug used to be the sales champion of GLP-1 drugs.
Sales reached 4.
37 billion U.
S.
dollars at the peak of 2017.
However, data in 2020 show that the drug market has entered Downturn period
.
Also under Novo Nordisk, Semaglutide has grown rapidly and has grown into another blockbuster drug with sales of US$3.
72 billion in three years.
The drug has two dosage forms: injections and oral preparations
.

  In the face of the menacing semaglutide, Eli Lilly’s "War Book" has been released
.
Its next major product in the Type 2 diabetes pipeline is Tirzepatide
.
Unlike GLP-1 receptor agonists, Tirzapatide has glucose-dependent insulin-promoting polypeptide (GIP) and GLP-1 dual receptor agonists
.
In March 2021, Eli Lilly's Phase III clinical study of Tizepatide and Semaglutide head-to-head comparison of SURPASS-2 was successful
.
Studies have shown that Tirzepatide 5mg, 10mg and 15mg doses are better than semaglutide in reducing patients' glycosylated hemoglobin levels and body weight
.
In addition, diabetic patients are often unable to adhere to treatment due to drug side effects
.
Although high-dose semaglutide and dulaglutide are effective, most patients prefer to use lower doses
.
In terms of low-dose treatment, Tirzepatide seems to have an advantage over Semaglutide
.
Of Tirzepatide's three trial dosage specifications, the 5 mg dosage specification will be used to submit marketing authorization applications, which will balance the impact of semaglutide on dulaglutide after the market
.

  The "multiple identities" of diabetes treatment drugs

  Novo Nordisk's income mainly comes from insulin, followed by GLP-1 drugs
.
However, in recent years, Novo Nordisk's insulin sales have declined due to factors such as falling prices and new US legislation forcing it to provide greater discounts to medical insurance
.

  At the beginning of 2020, Novo Nordisk's new indication for semaglutide subcutaneous injection (Ozempic) was approved by the US FDA.
The drug is used to reduce the risk of cardiovascular events in adult patients with type 2 diabetes and other cardiovascular diseases, including cardiovascular embolism.
, Non-fatal heart attack or non-fatal stroke
.
At the same time, Novo Nordisk also announced the update of the "clinical studies" section of the oral semaglutide (Rybelsus) prescribing information to include the analysis of the primary endpoint of the PIONEER 6 CVOT trial: PIONEER 6 cardiovascular outcome trial showed that oral semaru Compared with the placebo group, the peptide treatment group can significantly reduce the risk of cardiovascular events in patients
.

  Novo Nordisk stated that it will continue to carry out the PIONEER series of trials in the field of diabetes treatment
.
Among them, PIONEER Plus is used to explore the efficacy of high-dose oral semaglutide [25mg and 50mgQD (once a day)], and SUSTAIN FORTE is used to explore the efficacy of high-dose semaglutide injection [2mg QW (once a week)]
.
In addition, the effect of semaglutide subcutaneous injection on retinopathy of type 2 diabetic patients will be studied
.

  For other related indications, Novo Nordisk is also exploring boldly and carrying out large-scale clinical trials for patients with diabetes and other diseases
.
For example, for patients with type 2 diabetes with cardiovascular events or chronic kidney disease, a large clinical trial called SOUL involving nearly 10,000 patients will be carried out; for patients with type 2 diabetes with only moderate to severe chronic kidney disease, a large clinical trial called FLOW will be launched.
Clinical trials
.

  In addition to diabetes-related diseases, Novo Nordisk has also set its sights on the treatment of non-diabetic-related diseases such as non-diabetic obesity and Alzheimer’s disease.
For example, in December 2020, Novo Nordisk announced that it would carry out oral soma Phase III clinical study of Lutide in the treatment of Alzheimer's disease
.

  The expansion of indications has become a market growth point

  In December 2019, Sanofi announced that it would stop research on new drugs for the treatment of diabetes and cardiovascular diseases and shift to the field of autoimmunity and tumor treatment
.
Diabetes business was once one of Sanofi’s largest business segments.
The sales peak of its flagship product, insulin glargine (Lantus), once exceeded US$7 billion, and its other two diabetes treatment drugs, Lixisenatide and Lixisenatide.
Insulin Glulisine (Insulin Glulisine), the sales volume is very small, in recent years, Lantus' market share has also been eroded a little bit
.
Compared with Novo Nordisk and Eli Lilly, which have blockbuster new drugs in their hands, Sanofi not only lacks pipelines, but also almost completely wiped out several cooperative projects introduced through heavy money, such as the SGLT1/2 suppression co-developed with Lexicon.
Zynquista, the development of the drug Zynquista, was discontinued following the failure of clinical research on expanding indications
.

  Among the top ten sales of drugs in the diabetes field in 2020, two SGLT-2 inhibitors (dapagliflozin and enpagliflozin) are on the list
.
Compared with 2019, the sales of both have greatly increased, thanks to their expansion in heart failure indications
.
In May 2020, AstraZeneca’s dapagliflozin tablets became the first SGLT-2 inhibitor for the treatment of symptomatic chronic heart failure (HFrEF) with reduced ejection fraction.
This indication will be available in China in February 2021 Approved
.
Boehringer Ingelheim’s Empagliflozin followed closely.
In October 2020, Boehringer Ingelheim submitted its Diabetes Alliance’s Enpagliflozin tablets for the treatment of patients with or without diabetes and reduced ejection fraction.
The registration application for adult patients with heart failure has achieved simultaneous application and listing with Europe and the United States
.
However, for people with heart failure (HFpEF) with a larger ejection fraction retention (LVEF>49%), there is currently no drug approval, and usually only related drugs can be used to relieve symptoms or use drugs that treat HFrEF off-label
.
The key clinical studies of empagliflozin and dapagliflozin for the treatment of HFpEF are expected to release data this year.
The two clinical studies are the Emperor-Preserved (NCT03057951) of empagliflozin and the Deliver ( NCT03619213)
.
(China Medical News )