SGLT-2 inhibitors grow old without acceleration.

It's a big step forward for home-grown SGLT-2 inhibitors, but it has to be said that at the SGLT-2 inhibitors circuit, domestic Followers have to speed up and get old without accelerating.
the main function of SGLT-2 inhibitors The main function of the kidneys lies in the excretion of metabolic waste in the body and the re-absorption of substances such as water, sugar and salt.
Sodium Glucose cotransporters, SGLTs play a key role in renal glucose re-absorption, which is re-absorbed through SGLTs.
SGLTs can be divided into SGLT1 and SGLT2, where SGLT2 is responsible for 90% glucose re-absorption and SGLT1 is responsible for the remaining 10% glucose re-absorption.
between Table 1 SGLT1 and SGLT2 Normally, the re-absorption of glucose changes with blood sugar concentration.
blood sugar concentration is low, the kidney ball plays a heavy absorption role.
when blood sugar levels rise to a certain concentration, renal pelfring stops and excess glucose is excreted from the urine.
usually refers to elevated blood sugar and the blood sugar concentration that triggers glycemic urine as the renal sugar threshold, which is usually 10mmol/L for healthy people.
But for patients with type 2 diabetes (T2DM), the expression of SGLT2 improved, with a nephrotic sugar threshold of about 15% higher than in healthy people, further enhancing the re-absorption of glucose and maintaining blood sugar at high levels.
1 Changes in the renal sugar threshold in healthy subjects and patients with T2DM The key to lowering blood sugar under this mechanism is to reduce the re-absorption of glucose and excrete excess glucose.
because SGLT2 plays a leading role in re-absorption, inhibiting SGLT-2 re-absorption becomes the key to sugar reduction.
this idea, scientists have discovered the root psine.
is extracted from apple bark, and the affinity with SGLT is 1000-3000 times that of glucose.
this means that when the root pyrine is present, SGLT-2 will be preferred to bind to the root pyrine, do not play the role of re-absorption of glucose.
other words, the root pyside can block the channel action of SGLT-2 in the re-absorption of urine sugar, resulting in glucose can only be excreted through urine.
Figure 2 The chemical structure of the root pyside Because the chemical properties of the root pyside are not suitable for use as oral antisaccharides, in subsequent studies, scientists have chemically synthesized a derivative similar to the root pyside structure, suitable for oral use, and uniformly named sodium-glucose co-transport protein inhibitor (SGLT-2 inhibitor).
the mechanism of SGLT-2 inhibitors is not difficult to find, its sugar-lowering mechanism depends on the difference between blood sugar and urine sugar concentration.
, the advantage of SGLT-2 inhibitors is that when blood sugar concentrations are low, their sugar-lowering effect is significantly reduced, greatly reducing the risk of hypoglycemia.
But its disadvantages are also very obvious, one is due to kidney metabolism, for patients with abnormal renal function, sugar reduction function significantly weakened, and the other is that with the increase in urinary sugar concentration, the risk of infection in the reproductive tract of patients will also increase.
addition to its therapeutic effects on T2DM, SGLT-2 has been found in recent years to significantly reduce the incidence of adverse cardiovascular events (Major Adverse Cardiovascular Events, MACE) and heart failure (Heart Failure, HF).
EMPA-REG OUTHOME trial found a net 38 percent lower risk of cardiovascular death and a 35 percent hospitalization risk of heart failure compared to the control group.
CANVAS trial found a net 14 percent reduction in cardiovascular risk and a 33 percent hospitalization risk of heart failure, showing the advantages of SGLT-2 inhibitors in reducing the risk of cardiovascular death and heart failure.
SGLT-2 inhibitor market pattern Has been approved nine SGLT-2 inhibitors listed in the world, there are currently four approved for listing in China, namely, Dagle Net, Kagle Net, Engele Net and Agleg Net.
Evaluate Pharma predicts that by 2022, SGLT-2 inhibitors will surpass the $11.71 billion in DVP-4 drugs with annual sales of $13.26 billion, second only to insulin and GLP-1-1-subjectors.
Table 2 NMPA approved for listing of the four SGLT-2 inhibitors Chart 1 Dalgledge Net, Engel Net, Kagle Net 2014-2019 Global sales (US$100 million) Globally, Engel net sales have reached new highs, with sales exceeding US$3 billion in 2019.
the latest figures, Ingle's net global sales in the first half of 2020 were close to $2 billion.
At the same time, Ingley Net's new adaptation is progressing well, and on July 31, 2020, Grigg and Lilly jointly announced that the phase 3 clinical trial of Engele Net in the treatment of adult patients with reduced shot blood failure (HF) had reached its primary endpoint.
with the launch of the new allergen, Ingre's net sales are likely to be high.
's net sales have continued to suffer in recent years, at the heart of which is the FDA's black-box warning.
Black Box Warning is one of the FDA's most serious forms of warning for listed drugs, requiring bold black boxes to be added at the top and most prominent positions of the drug manual, which often have a more serious risk of side effects.
3, an antibiotic black box warned that in the CANVAS trial, the risk of lower limb amputation in the Caglie net group was about twice as high as in the placebo group.
in May 2017, the FDA added a black-box warning to Kaglile's drug instructions, an incident that significantly affected Caglie's net sales.
In August, the FDA decided to remove the black-box warning of amputation risk from Kaglia Net, taking into account the benefits of Kagle's net for heart and kidney disease, and to move the content to the "Warnings and Precautions" section.
July 29, 2020, Mercadon's Eglie net tablet listing application was approved by the State Drug Administration, becoming the fourth SGLT-2 inhibitor approved for listing in China.
has not yet had sales data flow out.
domestic SGLT-2 inhibitor research and development is in full swing domestic SGLT-2 inhibitor research and development is a hot, Hengrui Medicine, four-ring medicine (Xuanzhu Medicine), Dongsian are stepping up research and development.
September 30, 2020, Hengrui Pharmaceuticals submitted an application for the listing of a new class of proline hengle net tablets, adaptive to the treatment of type 2 diabetes, is expected to become the fifth domestic market SGLT-2 inhibitor.
, a heavy-weight product of Four Rings Pharmaceuticals, entered Clinical Phase III in January 2019 and is expected to be submitted to the NDA in 2021.
August 28 this year, The Ronggli Net III clinical debut in Dongsian, in patients with type 2 diabetes have better efficacy and safety.
addition, Tianjin Institute of Pharmaceutical Research's Tagle Net is currently in Clinical Phase II, Fosun Pharma (Wanbang, Jiangsu Province) Wangle Net, Shanghai Alice's Aegre Net are in Clinical Phase I.
addition to innovative drugs, the development of generics for SGLT-2 inhibitors is also in full swing.
data show that a total of six companies have submitted Ingley net generic drug listing applications, of which Haussen and Colum's generic drugs have been listed this year;
December 20, 2019, Haussen Pharmaceuticals' Kagle Net Tablet was approved for the market, successfully copying SGLT-2 inhibitors with a winning bid of 3.98 yuan/100 mg.
July 31, 2020, HAUSSEN Pharmaceuticals' four-class generic drug Engele Net Tablet was approved for market and evaluated as consistent.
August 14, 2020, Colum Pharmaceuticals' class 4 generic drug Engele Net Tablet was approved for the market.
September 28, 2020, Zhengda Tianqing Class 4 generic drug Kagli net tablets were approved for listing by NMPA.
the risks of stacking up, the SGLT-2 inhibitor circuit is very crowded, with the former having the first-mover advantage of the giants and then the generics companies chasing it.
Follower needs to be alert to the estability of new drug development, the sharp drop in prices and the risks of generics swarming.
alert to the errative nature of new drug development.
the SGLT-2 inhibitor circuit, Dagle Net has been listed in China for three years, and Caglia Net and Engel net listing has been two years.
iron rule of Fast Follow is that there is still some market space for follower within three years of the first drug's launch, and that follower, which is listed five years after the first drug, is extremely risky.
the three-year deadline is fleeting, leaving follower with limited time.
think back to the TNF-a circuit, although there are many followers, but Shumeile, Enley, like grams have always firmly occupied nearly 80% of the market share, the first advantage under the strong Hengqiang effect is very obvious.
be alert to the risk of sharp drops in drug prices.
November 2019, Ingrequin, Dagle net and Kagle net were included in the National Health Insurance Agency's 2019 National List of Essential Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drugs.
, Dagly net film for 4.36 yuan / 10mg price into the National Health Insurance Directory, a price reduction of 73%.
the net price of The Engele has also been sharply reduced to 4.24 yuan / 10mg, the net research price of Kagele is only 9.46 yuan / 100mg.
market share analysis, the current SGLT-2 inhibitors in the domestic diabetes market accounted for less than 1%, the original drug has encountered a sharp price reduction for later market opening up is very disadvantageous.
be wary of the risks of generics swarming in.
2020, SGLT-2 inhibitors are flooding in, and the low-cost strategy of generics is hitting the market for the original drug.
face of the invasion of generic drugs, after all, the huge cost advantages of generic drugs are there.
to a deeper level of analysis, SGLT-2 inhibitor adaptation is diabetes, with the concept of "two diseases" more and more hot, diabetes drugs into the belt procurement, it is possible that one day SGLT-2 inhibitors will enter the ranks of strip procurement.
by then, generic drugs were more easily and comprehensively crushed.
, just want to say that the follower of this track is going to accelerate, and then it's going to get old without accelerating.
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