Evidence-based escort, "pancreas" path to "secretion"-revealing the Chinese evidence of the safety of GLP-1RA pancreas

*Only for medical professionals to read for reference.
How safe is GLP-1RA in the pancreas of the Chinese population? The first evidence-based evidence revealed! At present, diabetes treatment strategies have changed from reducing blood sugar according to individualized goals 10 years ago to focusing on the control of patients' cardiovascular disease risk factors, and now emphasizing comprehensive management of cardiovascular outcomes [1-3]
.

In addition to the significant hypoglycemic effect, the "Rookie" Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) has cardiovascular benefits, and its status in the guidelines has gradually improved [1-3]
.

The 2020 edition of "China Type 2 Diabetes Prevention Guidelines"[3] pointed out that for patients with type 2 diabetes (T2DM) who are diagnosed with atherosclerotic cardiovascular disease (ASCVD) or high-risk factors, chronic kidney disease (CKD), it is recommended On the basis of life>
.

For patients who do not have ASCVD or high-risk factors, heart failure, or CKD, GLP-1RA is also an important treatment for dual combination therapy
.

While GLP-1RA has attracted much attention, the discussion on the safety of its pancreas has always been a clinically enduring topic
.

 Recently, a subgroup analysis of the AWARD-CHN2 study conducted by Professor Ji Qiuhe from the Department of Endocrinology and Metabolism of Xijing Hospital Affiliated to the Air Force Military Medical University was accepted by Diabetes Therapy and published online [4].
Hierarchical analysis of potential influencing factors of pancreatin changes has been conducted to evaluate the safety of pancreatic treatment with dulaglutide, which also provides important evidence for the clinical application of GLP-1RA in China
.

In this regard, the "medical community" invited Professor Ji Qiuhe to share the research
.

Pancreas safety is controversial, and evidence in China is still lacking.
Since Diabetes Care reported the first case of pancreatitis suspected of exenatide in 2006 [5], the relationship between GLP-1RA and acute pancreatitis has been controversial
.

In 2014, the U.
S.
Food and Drug Administration (FDA) and the European Medicines Agency (EMA) conducted a joint evaluation on the data of incretin drugs that have been marketed and under development in Europe and the United States, and it is believed that although the pancreatin level has slightly increased However, based on current evidence, it is impossible to conclude that there is a causal relationship between incretin and pancreatitis or pancreatic cancer [6]
.

Professor Ji Qiuhe pointed out that the above studies were carried out in Caucasians.
In the Chinese population, there is no specific analysis on the safety of GLP-1RA pancreas, so it is worthy of further discussion
.

 The AWARD-CHN2 study [7] is a multi-center, randomized, open, parallel-controlled phase 3 clinical study conducted in Asian populations, confirming the effectiveness of dulaglutide in combination with metformin and/or sulfonylureas Sex and safety
.

"At the same time, this study also comprehensively monitored the level of pancreatin, and the case of pancreatitis was determined by a third-party independent endpoint committee, so it is more objective and it is worth our in-depth analysis of these data
.

" Professor Ji Qiuhe said
.

 Subsequently, Professor Ji Qiuhe introduced that the AWARD-CHN2 post-mortem analysis [4] further adopted the important baseline characteristics of Chinese T2DM patients and potential influencing factors related to pancreatic safety [age, gender, diabetes course, baseline weight, baseline body mass index ( BMI), baseline glycosylated hemoglobin (HbA1c), baseline triglycerides (TG) and the use of combined oral hypoglycemic drugs] were stratified analysis to assess the safety of pancreatic treatment with dulaglutide
.

This post-event analysis will also provide the first evidence-based basis for the safety of GLP-1RA pancreas in the Chinese population
.

Evidence-based evidence to escort, "pancreas" path to "secret" what to do.
This post-mortem analysis included a total of 203 Chinese patients with T2DM who were treated with metformin and/or sulfonylurea in combination with dulaglutide for 26 weeks.
Later, the changes in pancreatic enzymes (including pancreatic amylase, total amylase and lipase) levels of patients in different stratified factor subgroups were observed
.

After analysis, after receiving 1.
5 mg of dulaglutide for 26 weeks, the patient's pancreatin level increased slightly within the normal range, and it was independently determined that it was not related to pancreatitis
.

The level of pancreatic amylase increased from baseline is at different ages (<60 years or ≥60 years), gender (male or female), baseline diabetes course (<10 years or ≥10 years), baseline weight (<70 kg or ≥ 70 kg), baseline BMI (<25 kg/m2 or ≥25 kg/m2), baseline HbA1c (<8.
5% or ≥8.
5%), baseline TG (<2.
3 mmol/L or ≥2.
3 mmol/L) and different combinations The subgroups of oral hypoglycemic drugs (only metformin, only sulfonylureas, or metformin combined with sulfonylureas) were similar between the subgroups, and there was no significant difference between these subgroups (P>0.
05) (Figure 1) [4]
.

Figure 1 Pancreatic amylase changes stratified according to potential influencing factors after 26 weeks of treatment.
In addition, similar results were observed in the subgroup analysis of total amylase and lipase changes from baseline (Figure 2 and Figure 3)
.

 Figure 2 After 26 weeks of treatment, changes in total amylase stratified according to potential influencing factors Figure 3 After 26 weeks of treatment, changes in lipase stratified according to potential influencing factors, Professor Ji Qiuhe concluded that this suggests that the level of pancreatin is mild The elevation is not specific in different patient populations, so we conclude that the pancreatic enzyme changes in T2DM patients treated with dulaglutide are not affected by potential factors related to pancreatic safety, including: age, gender, diabetes Course of disease, baseline weight, baseline BMI, baseline HbA1c, baseline TG, and the use of combined oral hypoglycemic agents [4]
.

"The reason for the mildly elevated pancreatin needs to be further explored, but for the clinical application of dulaglutide, it can be said to be safe
.

"Professor Ji Qiuhe added
.

Special populations need to pay attention to the safety of the pancreas .
Professor Ji Qiuhe emphasized that the clinical application of GLP-1RA is gradually widespread, and dulaglutide has cardiovascular benefits due to hypoglycemic reduction, and one week One injection is simple and easy to be accepted by patients, and clinical applications are gradually increasing, so the assessment of its safety is particularly important
.

 Previous studies have shown that there is no clear association between dulaglutide and pancreatitis, but most of them are performed in white people.
[8], and there are certain differences between Asian patients and Western patients in the etiology, risk factors, and incidence of pancreatitis
.
[9]
Therefore, this study is based on previous studies and through the potential impact of known pancreatic safety The factor grouping of patients carried out more in-depth exploration, not only taking into account the characteristics of the Chinese T2DM population, but also taking into account the risk factors of pancreatitis, which can more comprehensively analyze the pancreatic safety of dulaglutide [4]
.

 Professor Ji Qiuhe analysis At present, the number of elderly patients with diabetes in China is as high as 35.
5 million[10], which is a relatively high proportion
.

The results of this study show [4] that there is no significant difference in pancreatic enzyme changes in T2DM patients under 60 years old and over 60 years old in China.
That is, the pancreatic safety characteristics of dulaglycotide are similar, suggesting that dulaglycotide is a safe treatment option for elderly patients
.

 In addition, 60% of T2DM patients in China are overweight/obesity [11], and because GLP-1RA is simultaneously reducing blood sugar It can help patients manage their weight and is therefore one of the treatment options for overweight/obese diabetic patients[12-13]
.

However, obesity can increase the incidence and severity of acute pancreatitis[14], which makes it possible to explore GLP-1RA in The safety of the pancreas in overweight/obese T2DM patients is particularly important
.

Professor Ji Qiuhe said that this study showed that [4], whether the patient is overweight/obese or not, the changes in pancreatin levels are similar, suggesting that no matter whether the patient is obese or not, it is safe to receive dulaglutide treatment
.

 Professor Ji Qiuhe also pointed out that hypertriglyceridemia is also one of the important causes of acute pancreatitis [15]
.

Therefore, the evidence of pancreatic safety of GLP-1RA in patients with T2DM and hypertriglyceridemia is essential to support clinical treatment
.

This study found that patients treated with dulaglutide showed similar changes in pancreatin levels regardless of TG levels, suggesting that dulaglutide can be considered as T2DM with hypertriglyceridemia (TG ≥2.
3 mmol).
/L) Safe treatment options for patients [4]
.

However, for people with higher triglyceridemia (TG ≥5.
6 mmol/L), the current evidence is lacking, and further investigation is needed
.

 In addition to the above special populations that require clinical attention, the study also found that diabetic patients using dulaglutide, regardless of their gender and diabetic disease characteristics, such as the length of the disease, the control level of HbA1c, and the type of combined oral drugs (only metformin, only Regardless of sulfonylureas, or metformin combined with sulfonylureas), no problems related to the safety of the pancreas have been observed [4]
.

 All in all, this post-mortem analysis proved that pancreatic enzyme changes in Chinese T2DM patients treated with dulaglutide were not affected by potential factors related to pancreatic safety
.

For special populations such as elderly, obese, and T2DM patients with hypertriglyceridemia, as well as people with different diabetic disease characteristics, no potential problems related to pancreatic safety have been observed in dulaglutide treatment [4]
.

This post-mortem analysis provided evidence for the safety of GLP-1RA pancreas in the Chinese population for the first time, and provided an important reference for future diabetes treatment and clinical drug selection
.

Summary In recent years, with the increase of evidence-based evidence, people have found that GLP-1RA has significant hypoglycemic effects and some cardiovascular benefits.
Therefore, its status in the treatment of diabetes has been increasing, and it has been recommended by authoritative guidelines at home and abroad [ 3,16]
.

For the clinical application of this new type of hypoglycemic drugs, such as dulaglutide, as a weekly GLP-1RA preparation, its hypoglycemic effectiveness and safety have been clinically verified [17], and cardiovascular benefits are also determined by cardiovascular outcomes.
Studies have confirmed [18] that, in order to be more at ease in clinical applications, the safety of the pancreas also needs more evidence to support it
.

Through the post-event subgroup analysis of the AWARD-CHN2 study, the pancreatic safety of dulaglutide in Chinese patients was confirmed
.

Looking forward to the future, with the wider application of GLP-1RA drugs, it can bring more benefits to Chinese patients
.

Expert profile Professor Ji Qiuhe · Department of Endocrinology and Metabolism, Xijing Hospital Affiliated to Air Force Military Medical University · Chief Physician, Professor, Doctoral Tutor · Vice Chairman of Diabetes Branch of Chinese Medical Association · Honorary Chairman of Diabetes Branch of Shaanxi Medical Association · Military Endocrinology Deputy Chairman of the Professional Committee of Metabolic Diseases · Standing Committee Member of the Endocrinology and Metabolism Physicians Branch of the Chinese Physician Association · Deputy Editor-in-Chief of "Chinese Journal of Diabetes" and "International Journal of Endocrinology and Metabolism" "Chinese Journal of Endocrinology and Metabolism", "Chinese Journal of Diabetes", "Medical Journal of the People's Liberation Army ", "Drug Evaluation", "Diabetes/Metabolism Research and Reviews" and other editorial references: [1] Diabetes Branch of Chinese Medical Association.
Peking University Medical Press.
2011.
[2] Jia Weiping, et al.
Chinese Journal of Diabetes.
2018;10(1):4-67.
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[4]Zhou Y, et al.
Diabetes Ther.
2021 Aug 28.
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[7]Yan Li, et al.
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[9]Yadav D, Lowenfels AB.
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[10]Sinclair A, et al.
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[11]Wang L, et al.
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[13]Carls GS, et al.
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[14]Khatua B, et al.
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[15]Hansen SEJ, et al.
The Journal of clinical endocrinology and metabolism.
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[17]Burness CB, Scott LJ.
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[18]Gerstein HC, et al .
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-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 submission/reprint/business cooperation, please contact: pengsanmei@yxj .
org.
cn43(suppl 1):s98-s110.
[17]Burness CB, Scott LJ.
BioDrugs.
2015;29:407–418.
[18]Gerstein HC, et al.
Lancet.
2019;394(10193):121-130 .
-End-"This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position.
" For submission/reprint/business cooperation, please contact: pengsanmei@yxj.
org.
cn43(suppl 1):s98-s110.
[17]Burness CB, Scott LJ.
BioDrugs.
2015;29:407–418.
[18]Gerstein HC, et al.
Lancet.
2019;394(10193):121‑130 .
-End-"This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position" for submission/reprint/business cooperation, please contact: pengsanmei@yxj.
org.
cn