Strength "Hard and Rigid" Sugar-lowering Ceiling——Expert Authoritative Interpretation of SURPASS Research

*Only for medical professionals to read for reference.
Existing data shows that the blood glucose compliance rate of patients with type 2 diabetes is less than 60%
.

See how experts authoritatively analyze how Tirzepatide achieves the "hard and rigid" hypoglycemic ceiling, explores blood glucose standards, and achieves blood glucose normalization
.

Recently, at the annual meeting of the American Diabetes Association (ADA), the results of the SURPASS series of studies were announced, allowing us to recognize a new hypoglycemic drug—glucose-dependent insulin-promoting polypeptide (GIP)/glucagon-like peptide-1 ( GLP-1) dual-receptor agonist weekly preparation-Tirzepatide (TZP), and its clinical trial performance in the whole course of type 2 diabetes (T2DM) disease, single drug, combined oral drug, and insulin treatment stage
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 The results of its clinical trials immediately aroused widespread concern and heated discussions in the endocrinology community
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In this regard, "Medical Circle" made a special trip to visit authoritative experts in the field of endocrinology-Professor Ji Linong from Peking University People's Hospital, Professor Mu Yiming from PLA General Hospital, and Professor Peng Yongde from Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, and invited 3 experts to discuss the results of this series of studies.
Made an in-depth analysis for the majority of colleagues
.

 Unique mechanism, with a blood glucose compliance rate exceeding 90%.
Professor Ji Linong introduced that as an innovative hypoglycemic drug, TZP has a unique hypoglycemic mechanism that can simultaneously stimulate GIP receptors and GLP-1 receptors, thereby promoting insulin secretion and other pharmacological effects.
Role
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"GLP-1 receptor agonists have been confirmed by a number of studies and clinical practice to have a strong blood sugar improvement effect, while improving blood lipids, blood pressure and weight control; GIP receptor agonists also have a good hypoglycemic effect
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The TZP, which is a combination of the two, exhibits stronger blood sugar, blood pressure, blood lipids and weight improvement effects
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The SURPASS series of studies explored the effectiveness and safety of TZP in different T2DM patients and medication regimens, and found that the proportion of HbA1c (less than 7%) in the TZP group was significantly higher than that of the control group.
In the high-dose group Even more than half of the subjects' HbA1c reached less than 5.
7%, that is, blood glucose returned to normal
.

For example, in the SURPASS-1 study, for no hypoglycemic drugs or no hypoglycemic drugs within 3 months before enrollment, the baseline HbA1c is 7.
In 94% of patients with early T2DM, TZP monotherapy can achieve blood glucose standard in about 90% of patients (HbA1c<7%).
It can be seen that TZP can effectively lower blood sugar in the early stage of T2DM
.

Professor Ji Linong believes that this means TZP will be a very good treatment for newly diagnosed T2DM patients.
TZP injected once a week can help most T2DM patients achieve blood glucose standards, and even help some patients to reduce blood glucose to the normal range
.

Such treatment and curative effects can not only Improving patient experience can also enhance their confidence in managing diabetes
.

 Professor Peng Yongde interpreted the SURPASS-2 and 3 studies of T2DM patients who have been combined with oral drugs in the advanced stage of the disease
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He introduced that incretin is two major types of hormones.
One is GLP-1 and the other is GIP
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In the past, we paid more attention to GLP-1.
For example, the newly marketed weekly preparation smeglutide is an excellent GLP-1 RA, which can reduce blood sugar and weight, Cardiovascular protection and hypoglycemia risk are outstanding
.

In addition, insulin degludec, as a newly marketed long-acting insulin analog, has a long acting time and stable onset, and it is also very advantageous in similar drugs
.

 From the SURPASS-2 and 3 studies, it can be seen that the GIP/GLP-1 dual receptor agonist TZP is compared head-to-head with simeglutide and insulin deglu, and the performance of TZP is significantly better than these two" "Predecessors": In the two studies, half of the patients' HbA1c fell within the normal range of 5.
7% after TZP 15mg treatment, while simeglutide and insulin deglubber could only achieve this in 20% and 5.
4% of patients, respectively.
Goal, it can be seen that TZP has better hypoglycemic effect than GLP-1 RA and long-acting basal insulin analogs [2, 3]
.

 Professor Mu Yiming added that it is difficult for patients who have been combined with insulin therapy to achieve blood glucose control standards.
Even in patients who use intensive therapy or insulin pump therapy, the rate of compliance with HbA1c less than 7% is less than 60%
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In the SURPASS-5 study, after combined treatment with TZP in T2DM patients with a longer course, more than 90% of patients reached the standard for blood glucose, and even 60% of patients had normalized blood glucose [4]
.

"This result is quite amazing
.
In
previous studies, we have almost never seen such a high blood glucose compliance rate.
At the same time, the risk of hypoglycemia has not increased significantly, and even the amount of insulin can be reduced, which is surprising
.

Dual agonists It must be through a broader mechanism of action to control and stabilize blood sugar.
This mechanism is worthy of our further discussion in the future
.

" "We look forward to the fact that this drug has undergone sufficient clinical studies to verify its effectiveness and safety.
, Can play a very important role in the control of diabetes, including weight loss and even the improvement of fatty liver
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"Professor Ji Linong said
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 All-rounder for sugar control and weight loss, taking into account the efficacy and safety effectiveness is one aspect, and safety is also very important to clinicians
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How safe is TZP? Several experts gave affirmative answers
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 Professor Ji Linong said that according to the currently published research data, the main safety problem of TZP is similar to that of GLP-1RA, that is, gastrointestinal adverse reactions, and the degree is mostly mild to moderate; monotherapy does not cause hypoglycemia, which is comparable to placebo.
In contrast, the risk of hypoglycemia did not increase significantly [1]
.

 In a head-to-head comparison with deglu-insulin and smeglutide, the incidence of hypoglycemia in TZP is lower than that of deglu-insulin, and its safety and tolerability are consistent with smeglutide
.

Professor Yongde Peng believes that when combined with oral hypoglycemic drugs, TZP can take into account the effectiveness and safety of hypoglycemic agents, and can be applied to more T2DM populations [2, 3]
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 Professor Mu Yiming pointed out that insulin is a very common and potent hypoglycemic drug for many diabetic patients (especially those with long-term T2DM), but it may increase weight and risk of hypoglycemia
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For elderly patients with heart, brain, and kidney complications, hypoglycemia is very dangerous and harmful
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At the same time, due to insulin resistance and other reasons, even if a large dose of insulin is used in some patients, the blood glucose compliance rate is still unsatisfactory
.

 In response to this situation, the usual international practice is to use insulin and GLP-1 RA in combination to improve the effect of glucose control and reduce side effects
.

But this ADA conference provides us with a new idea-as a GIP/GLP-1 dual receptor agonist, TZP has better blood glucose management effects
.

According to the SURPASS-5 study, after TZP combined with basal insulin treatment, the patient not only improved blood sugar significantly, but also had a significant weight loss without increasing the risk of hypoglycemia [4]
.

Therefore, for patients with a long course of disease and poor blood sugar control, TZP is a hypoglycemic option that takes into account both effectiveness and safety.
Combined insulin therapy can complement the mechanism to help patients with long-term and poorly controlled T2DM achieve blood glucose standards, and even reduce blood sugar to normal.
scope
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Regardless of the length of the disease, a major feature of the SURPASS series of studies throughout the management of the whole process is to include patients from early single-drug therapy to late-stage combined insulin therapy, and observe the efficacy and safety of TZP in diabetic patients with different lengths of disease
.

 Specifically, the patients in the SURPASS-1 study had an average disease course of 4.
7 years, and TZP was used as the initial monotherapy [1]; the patients in the SURPASS-2 and 3 studies had an average disease course of 8.
6 years and 8.
4 years, and metformin (combined or not) Combined with sodium-glucose cotransporter 2 inhibitors) to treat poor blood glucose control [2, 3]; while in the SURPASS-5 study, patients had an average course of 13.
3 years, and insulin glargine (with or without metformin) was used to treat poor blood glucose control.
[4]
.

 In different types of patients, TZP monotherapy or combined with other drug treatments have significant effects, and HbA1c and body weight are greatly reduced, and at the same time, it does not increase the risk of hypoglycemia compared to the control group
.

Professor Peng Yongde commented: “Therefore, in combination with these studies, regardless of the length of the disease, regardless of whether the patient is in early, middle, or late diabetes, TZP can effectively reduce blood sugar and weight without increasing the risk of hypoglycemia
.

These research results make People are very excited and encouraged
.

"It will play a greater role in the future treatment of diabetes.
What is the significance of this safe and effective hypoglycemic drug for the future treatment of diabetes? Professor Mu Yiming introduced that at present, about 60% of adults in China are overweight and obese.
T2DM patients have a higher proportion of overweight and obesity.
Overweight and obesity are very harmful to T2DM patients and can significantly increase cardiovascular risks
.

Therefore, it is necessary to balance the relationship between blood sugar control and weight control during treatment
.

 As a GIP/GLP-1 dual-receptor agonist, TZP can command the brain and pancreas to co-process blood sugar, regulate the basic state of insulin and glucagon, and help diabetic patients control food intake, reduce hunger, and effectively control weight
.

Studies have shown that TZP promotes weight loss significantly better than other hypoglycemic drugs such as metformin
.

Existing evidence suggests that TZP will play a greater role in diabetes treatment in the future, especially for overweight and obese patients
.

 Professor Mu Yiming added that according to the current research data, TZP has demonstrated excellent anti-diabetic and weight-lowering effects, and good safety without increasing the risk of hypoglycemia.
It can normalize HbA1c in more than half of patients, reduce insulin dosage, and even reduce the amount of insulin.
After 40 weeks of treatment, the insulin dose used at baseline is less than that of the current marketed drugs
.

Regarding the applicable population of TZP, he believes that the course of the disease may not be a major consideration
.

 "I think that after the drug is launched, it will cover more people, whether it is newly diagnosed diabetic patients, short-term, medium-term or long-term patients, it can show better efficacy and safety
.

" Professor Ji Linong It is believed that if the cardiovascular safety or cardiovascular protection of TZP can be confirmed in future studies, it will hopefully enter the first-line treatment of diabetes
.

Its therapeutic effects in pre-diabetic patients, such as whether it can prevent diabetes and reverse pre-diabetes, are also worth looking forward to
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 Expert profileProfessor Ji Linong, director of the Department of Endocrinology, Peking University People's Hospital, director of Peking University Diabetes Center, chairman of the Endocrinology and Metabolic Disease Branch of the Chinese Association for Geriatric Care, Vice President of the Chinese Stroke Society, Vice President of the Endocrinology and Metabolism Physicians Branch of the Chinese Association of Physicians, and former editor-in-chief of the Chinese Journal of Diabetes Chairman of Diabetes Branch of Chinese Medical Association, Vice Chairman of International Diabetes Federation, Chairman of International Diabetes Federation Western Pacific Region (IDF-WPR) Expert Profile Professor Mu Yiming Chief Physician of Chinese People's Liberation Army General Hospital Professor of Tsinghua University School of Medicine, Doctoral Supervisor, Nankai University Professor, Doctoral Supervisor, Medical College, Director of the Department of Endocrinology, PLA General Hospital; Former Chairman, Chinese Medical Association Endocrinology Branch; President Designate, Chinese Medical Doctor Association, Endocrinology and Metabolism Physician Branch; Chairman, PLA Medical Association Endocrinology Professional Committee; Director, Beijing Medical Association, Endocrinology Branch Committee member "Chinese Journal of Internal Medicine", "Chinese Journal of Endocrinology and Metabolism", "Chinese Journal of Frontiers in Medicine" and "Journal of Practical Internal Medicine", "Journal of Pharmaceutical Evaluation", deputy editor of "Journal of Drug Evaluation", published more than 200 SCI papers and expert profiles Professor Yongde Peng Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor, Director of the Department of Endocrinology and Metabolism, Shanghai Jiaotong University First People's Hospital, Director of Thyroid Diseases Clinic, Director of Osteoporosis Joint Clinic, Deputy Director of Endocrinology Branch of Chinese Medical Association, and Leader of Basic Science Group, Chinese Society of Geriatrics Geriatric Endocrinology and Metabolic Diseases Branch Vice Chairman, Shanghai Medical Association Endocrinology Branch Chairman, Basic Science Group Leader, Chinese Medical Doctor Association Endocrinology and Metabolism Physician Branch Standing Committee Vice Chairman Chinese Diabetes Association Reference: [1] Rosenstock J, Efficacy and Safety of Once Weekly Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist Versus Placebo as Monotherapy in People with Type 2 Diabetes (SURPASS-1).
ADA 2021, Oral Presentation Number 100-OR.
[2] Frias JP.
Efficacy and Safety of Tirzepatide versus Semaglutide Once Weekly as Add-on Therapy to Metformin in People with Type 2 Diabetes (SURPASS-2).
ADA 2021, ePoster Number 84-LB.
[3] Ludvik B.
Efficacy and Safety of Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, Compared to Insulin Degludec in Patients with Type 2 Diabetes (SURPASS-3).
ADA 2021, ePoster Number 78-LB.
[4] Dahl D.
Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5).
ADA 2021, ePoster Number 80-LB.
-End- "This article is only used to provide scientific information to healthcare professionals, Do not represent the position of the platform" for submission/reprinting/business cooperation, please contact: pengsanmei@yxj.
org.
cnCompared to Insulin Degludec in Patients with Type 2 Diabetes (SURPASS-3).
ADA 2021, ePoster Number 78-LB.
[4] Dahl D.
Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5).
ADA 2021, ePoster Number 80-LB.
-End- "This article is only used to provide scientific information to medical and health professionals and does not represent the position of the platform" For business cooperation, please contact: pengsanmei@yxj.
org.
cnCompared to Insulin Degludec in Patients with Type 2 Diabetes (SURPASS-3).
ADA 2021, ePoster Number 78-LB.
[4] Dahl D.
Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5).
ADA 2021, ePoster Number 80-LB.
-End- "This article is only used to provide scientific information to medical and health professionals and does not represent the position of the platform" For business cooperation, please contact: pengsanmei@yxj.
org.
cn