What is the truth about multiple benefits beyond hypoglycemia?

*Only for medical professionals to read and reference At 8:30 on April 23rd, we invite you to talk about the new era of GLP-1RA
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 The battle between us and diabetes started more than 3,500 years ago[1].
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In order to win this battle and better treat diabetes, new hypoglycemic drugs emerge in an endless stream, glucagon-like peptide-1 Receptor agonists (GLP-1RA), as one of the drugs that have received much attention, are our protagonists today
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So how much do you know about the GLP-1RA? Do you understand the mechanism of multiple benefits of GLP-1RA such as hypoglycemic and weight loss? What is the secret behind the cardiovascular protective effect of GLP-1RA? Why do only some GLP-1RAs have cardiovascular benefits and not all? Next, I'll tell you the story.
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Who is it that I leave behind? Diabetes is a chronic non-communicable disease closely related to life>
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According to the latest data from the International Diabetes Federation (IDF) [3], there are 141 million adult diabetic patients in China
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Faced with such a situation, the "Healthy China Action (2019-2030)" issued by the state clearly stated [4] that China will carry out prevention and control actions against diabetes
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 Type 2 diabetes mellitus (T2DM) patients are prone to complications of cardiovascular, renal, ocular and other diseases [5]
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Most patients require multi-drug combination therapy, which increases the economic burden of patients and reduces compliance
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Based on this, drugs that take into account hypoglycemic, weight loss and cardiovascular protection have become an urgent need in the field of diabetes
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In recent years, some GLP-1RAs with significant hypoglycemic effects and cardiovascular benefits have made their debut as "new stars" in the hypoglycemic field
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 Thanks to the multiple benefits of GLP-1RA, its recommendation level in major diabetes guidelines continues to rise
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Throughout the "China Guidelines for the Prevention and Treatment of Type 2 Diabetes" (hereinafter referred to as "CDS Guidelines") from 2013 to 2020, the status of GLP-1RA has steadily increased [6-8]
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The latest guidelines pointed out [8] that patients with T2DM with atherosclerotic cardiovascular disease (ASCVD) or high risk of cardiovascular risk, regardless of whether their glycated hemoglobin (HbA1c) is up to standard, should be added to metformin as long as there are no contraindications.
With GLP-1RA or sodium-glucose cotransporter-2 inhibitor (SGLT-2i) with evidence of ASCVD benefit
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Even in 2022, the status of GLP-1RA in the "Standards of Diabetes Care" issued by the American Diabetes Association (ADA) has been further improved [9]
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In just a few years, the GLP-1RA achieved a "qualitative leap"
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Multiple benefits? What is the mystery behind this? As a new type of hypoglycemic drug, GLP-1RA has attracted much attention in recent years, so do you know that scientists have been exploring it since the early 1900s, and it has a history of nearly 120 years now.
in continuous research and development
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 As a hypoglycemic drug, hypoglycemic is its "first meaning"
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GLP-1RA stimulates insulin secretion and inhibits glucagon secretion in a glucose concentration-dependent manner by activating GLP-1 receptors, and increases glucose uptake in muscle and adipose tissue, thereby achieving a hypoglycemic effect [8, 10, 11]
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In addition to effective hypoglycemia, GLP-1RA has also been shown to reduce body weight and improve central obesity [12]
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In GLP-1RA, it can suppress appetite, inhibit gastric emptying, and increase energy expenditure [13]
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A multi-pronged approach to help patients lose weight easily
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 At present, GLP-1RAs that have been marketed in China include exenatide, liraglutide, polyethylene glycol loxenatide, dulaglutide and other drugs
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Among them, pegylated loxenatide is the first domestic GLP-1RA weekly preparation and the world's first pegylated long-acting hypoglycemic drug
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The unique polyethylene glycol modification technology endows polyethylene glycol loxenatide with many advantages, including prolonging the half-life, increasing the aqueous solution of the drug, taking effect within 1 hour after injection, and reducing the toxic and side effects of the drug, etc.
[14-16]
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The results of the study [17] showed that polyethylene glycol loxenatide can safely and effectively reduce blood sugar, with a reduction of HbA1c of 1.
14%, and no serious hypoglycemia events occurred
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 GLP-1RA will have gastrointestinal adverse reactions such as nausea and vomiting after application [8]
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However, a meta-analysis showed that [17], compared with the control group, pegylated loxenatide had a lower incidence of gastrointestinal adverse events, and seldom affected treatment
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It has the characteristics of long-acting, effective and safe hypoglycemic, and also has the characteristics of balanced benefit.
It can be used as a monotherapy or an additional drug for other hypoglycemic therapy, and it is an ideal choice for diabetic patients
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GET New Views: Double Exposure & Similar Effects The substantial rise of GLP-1RA in guidelines in recent years is due to the emergence of a large amount of evidence of its cardiovascular benefits, and the release of a large number of cardiovascular outcome trials (CVOT) results let the world see part of the GLP -1RA has a clear cardiovascular benefit
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GLP-1RA can reduce the risk of major adverse cardiovascular events (MACE) by inhibiting the proliferation of vascular smooth muscle cells and vascular endothelial cells, and exert its cardiovascular protective effect[13]
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#But why is the same GLP-1RA, only part of it has cardiovascular protection? What's behind the cardiovascular benefits? Some studies have shown that the cardiovascular benefits of GLP-1RA may not be related to structure and homology, but depend on the dual additive effects of time exposure and supraphysiological dose exposure [18, 19]
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That is to say, no matter what structure GLP-1RA is derived from, as long as the patient is exposed for a long enough time and the dose is exposed enough, GLP-1RA can exert its cardiovascular protective effect
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Thus, cardiovascular benefit can be considered as a class effect of all GLP-1RAs, all of which have cardiovascular protective effects [20, 21]
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 #Then how to achieve double exposure? What is the class effect? ​​What we know about GLP-1RA is its powerful hypoglycemic effect and weight loss benefits, and there are still many unknowns waiting for us to explore
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 In order to bring the mystery behind the multiple benefits of GLP-1RA, new progress in the field of GLP-1RA, and more cutting-edge information in the field of diabetes to the majority of colleagues
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On April 23, 2022, the "Harmony and Beauty World Summit Forum" held by Hansen will be grandly opened
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This summit forum will be jointly held offline and online.
It will join hands with authoritative experts in the field of diabetes at home and abroad to gather at the event to answer the known and unknown of GLP-1RA, and answer many of the above doubts, so stay tuned! Together in the same boat, and Morayford! See you on April 23rd! Scan the QR code below to watch the live conference! References: [1].
Chen Dongfang.
Medicine World.
2007;(10):25-29.
[2].
Ma RCW.
Diabetologia.
2018 Jun;61(6):1249-1260.
[3].
IDF Diabetes Map 2021.
https://diabetesatlas.
org/data/en/country/42/cn.
html[4].
Healthy China Initiative (2019-2030).
http:// /s3585u/201907/e9275fb95d5b4295be8308415d4cd1b2.
shtml[5].
Zhang Yongjun.
Journal of China Jiliang University.
2002;(03):82-86.
[6].
:2-42.
[7].
Diabetes Branch of Chinese Medical Association.
Chinese Journal of Practical Internal Medicine.
2018;38(04):292-344.
[8].
Diabetes Branch of Chinese Medical Association.
Chinese Journal of Diabetes.
2021;13 (4):315-409.
[9].
American Diabetes Association.
Diabetes Care.
2022;45(Suppl.
1):S1–S264.
[10].
Drucker DJ.
Cell Metab.
2006;3:153–165.
[11].
Zhang Xian, Tan Xiangshan, Ji Liwei.
Journal of Clinical Drug Therapy.
2018;16(10):13-16.
[12].
Guja C, et al.
Diabetes Obes Metab.
2018;2(23):28- 32.
[13].
Ji Linong, Zou Dajin, Hong Tianpei, et al.
Chinese Journal of Diabetes.
2018;26(05):353-361.
[14].
Drug Discov Today.