Summit Dialogue: Banting winners and Professor Xiao Xinhua talked about ADA academic hotspots and discussed the current status and future of diabetes treatment

*Only for medical professionals to read for reference, Professor Jens Juul Holst and Professor Xiao Xinhua of Peking Union Medical College Hospital jointly discussed the new methods of diabetes treatment in the future.
The most interesting topics in the ADA conference are the American Diabetes Association (ADA) annual meeting as the basis for the global diabetes field, The academic feast of clinical and nursing, every year will focus on the display of new technologies, new ideas, and new methods in the field of diabetes
.

Professor Jens Juul Holst, who has participated in the ADA annual meeting for 40 consecutive years, mentioned in an interview: "As usual, the content of this year's ADA conference is still very rich.
It is too late to learn, think and absorb.
Of course, I am most interested in talking about it.
That content"
.

Professor Xiao Xinhua believes: “The annual blockbuster award-the Banting Scientific Achievement Award, is the highlight of the conference
.

This year this award was given to Professor Holst, in recognition of his nearly 40 years of experience with glucagon-like substances.
The research history of peptide-1 (GLP-1) is well-deserved
.

In addition, the diagnosis and treatment of diet, intestinal flora, biological clock, and special types of diabetes are of great concern to clinicians
.

"Where is the future research direction of GLP-1? Professor Jens Juul Holst is one of the founders of incretin-related research.
He has made many pioneering contributions in the field of incretin, and therefore won this year's Banting Scientific Achievement Award.
Professor Holst at this ADA conference The discovery process, action fragments and hypoglycemic mechanism of GLP-1 were elaborated
.

Regarding the future research direction of GLP-1, Professor Holst said: “We still don’t know much about the effects of GLP-1 on the cardiovascular and kidneys.
Current studies have shown that GLP-1 receptors appear to also exist on vascular endothelial cells.
Perhaps it can explain the protective effect of GLP-1 in the cardiovascular system
.

In addition, the multiple effects of GLP-1 (such as appetite suppression, anti-inflammatory, etc.
) and GLP-1 receptor agonists (GLP-1RA) The multiple agonists within are the hotspots of future exploration and research
.

” Professor Xiao said: “Professor Holst has been committed to the study of GLP-1, and its mechanism of glucose-dependent hypoglycemic action on the pancreas has been studied thoroughly, but Professor Holst believes At present, the mechanism of GLP-1 on cardiovascular and renal protection still needs to be explored in many aspects
.

In addition, weight loss is also its interest and direction of research
.

At present, Professor Holst's team is committed to studying the effects of metabolic surgery on weight loss and diabetes relief The mechanism, including the key role of postoperative GLP-1 elevation, is hoped that more new drugs will emerge in the future instead of surgical treatment, which can relieve diabetes and obesity
.

"Clinically, GLP-1 receptor agonists and SGLT- 2How to choose the application of inhibitor? Cardiovascular disease (CVD) is the main cause of death for diabetic patients, and the global incidence of diabetic nephropathy is also increasing year by year.
Almost 40% of type 2 diabetes (T2DM) patients are accompanied by chronic kidney disease (CKD).
T2DM patients undergoing dialysis 5 The annual survival rate is only 40%, which brings a huge physical and economic burden to patients
.

Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has been confirmed by studies to have dual protective effects on the heart and kidneys
.

The cardioprotective effect of GLP-1RA has been confirmed, but there is no definite evidence for the renal protective effect
.

In clinical practice, how to choose these two types of drugs for T2DM patients with CVD and CKD is also a topic of general concern to clinicians
.

Professor Holst mentioned: “To apply SGLT-2i and GLP-1RA in clinical practice, it is very important to understand their mechanism of action
.

The protective effect of GLP-1RA on the cardiovascular system may take 1 to 2 years.
I see, so it needs to be used in advance and long-term
.

And because GLP-1RA can accelerate the heart rate clinically, although it only increases by 2~5bpm on average, it is not considered for the treatment of acute heart failure, but long-term use of GLP-1RA will be to a certain extent Reducing the risk of heart failure and cardiovascular disease has long-term significance for the prevention and treatment of cardiovascular disease
.

On the contrary, the mechanism of SGLT-2i to reduce the volume makes it have an immediate effect after treatment, and can be used to treat the heart bad
.
"Professor
Xiao views with Professor Holst basically the same, he believes, compared to GLP-1RA, SGLT-2i benefit earlier, evidence of benefit, especially in heart failure, CKD aspects more fully, GLP-1RA The benefits in atherosclerotic cardiovascular disease (ASCVD) are more significant, and the time required to benefit is longer than that of SGLT-2i
.

If the patient belongs to a high-risk group of ASCVD or has been diagnosed with ASCVD, GLP-1RA or SGLT-2i can be selected
.

However, if the patient is accompanied by CKD and heart failure, the current guidelines recommend SGLT-2i first; for T2DM patients with CKD, if SGLT-2i cannot be used, GLP-1RA can be considered
.

At present, GLP-1RA also has CKD and heart failure research underway.
I believe there will be more evidence for GLP-1RA in the near future
.

It’s very interesting that Professor Holst and Professor Xiao both mentioned the combined application of these two types of drugs, and their views on this are basically the same.
They believe that the two types of drugs have different mechanisms of action and conform to the principle of combination drugs, but they are combined.
Whether it will bring about superimposed effects needs further confirmation
.

Comparing four hypoglycemic drugs with different mechanisms of action, what is the clinical significance of the GRADE study? At this ADA annual meeting, a new study was also announced-GRADE study.
The study was led by Professor David Nathan, Director of the Center for Diabetes and Clinical Research of Harvard Medical School, and was conducted in 36 centers in the United States.
A randomized controlled clinical trial aimed at comparing the baseline medication of metformin in combination with four different mechanisms of action hypoglycemic drugs [GLP-1RA Liraglutide, sulfonylurea glimepiride, dipeptidyl peptidase 4 inhibitor (DPP) -4i) The effectiveness and safety of sitagliptin and basal insulin glargine]
.

The main outcome measure was the time to the first occurrence of glycosylated hemoglobin (HbA1c) ≥ 7% in dual therapy (Figure 1)
.

Figure 1 The outcome indicators and treatment plan results of the GRADE study showed that within three months after the start of treatment, the HbA1c level of each group of patients decreased significantly, but as time progressed, the HbA1c level of each group gradually increased, and finally On average, 71% of patients had HbA1c levels exceeding 7% (follow-up for 4 years), with the highest proportion of patients in the sitagliptin group (77%), followed by glimepiride (72%), insulin glargine and liraru The levels in the peptide group were similar (67% vs 68%)
.

In terms of the time required for HbA1c≥7% after treatment in each group, the liraglutide group had the longest time, with an average of 882 days, 21 days longer than the insulin glargine group, 72 days longer than the glimepiride group, and more There were 185 days longer in the Ting group (Figure 2)
.

In terms of cardiovascular benefits, the GRADE study showed that the incidence of cardiovascular disease in the liraglutide group was the lowest, 7.
6% in the insulin glargine group, 8.
0% in the glimepiride group, and 8.
6% in the sitagliptin group.
In the liraglutide group, only 5.
8% (P=0.
048)
.

Regarding the results of the GRADE study, Professor Holst commented: "The results of the GRADE study show the cardiovascular protective effect of GLP-1RA.
This is very exciting.
The study has a long follow-up period and the study design is in line with clinical practice
.

" Professor Xiao Xinhua believes: "The main result of the GRADE study is to clarify which dual drug is the appropriate choice on the basis of metformin after metformin treatment does not meet the standard
.

As a result, we have seen that when metformin treatment is not well controlled, Combined with GLP-1RA and Liraglutide, it takes the longest time to maintain blood glucose up to the target, and the incidence of hypoglycemia is also the least
.

In addition, GLP-1RA also has benefits in terms of weight loss, lowering lipids, lowering blood pressure, and cardiovascular benefits trend
.

United basal insulin or sulfonylurea drugs in a long time to maintain blood glucose, but hypoglycemia and weight gain risks are higher
.

United DPP-4i group Although hypoglycemia incidence is not high, but also weight However, it has the shortest time to maintain blood glucose up to the target, and the combination therapy fails very early when the initial glycation level is high
.

It can be seen that the combined benefit of metformin combined with GLP-1RA is the largest
.

"Figure 2 The main findings of the GRADE study The use of hypoglycemic drugs with cardiovascular protection is low.
How to change the status quo? This ADA annual meeting again announced some post-mortem analysis of CAPTURE research
.

The CAPTURE study is a global cross-sectional study that collected data from more than 9,800 T2DM patients in 13 countries.
The results showed that the use rate of SGLT-2i and GLP-1RA two new types of hypoglycemic drugs is low, and their use is similar to It is irrelevant whether it is combined with CVD disease, especially in young patients with a short course of disease.
The use rate is also extremely low.
This is contrary to the recent guidelines recommended in the application of CVD and CV high-risk groups
.

The CAPTURE study showed that in T2DM patients with CVD, less than one-fourth of the patients used hypoglycemic drugs with cardiovascular protection
.

The CAPTURE China subgroup study shows that 33.
9% of T2DM patients suffer from CVD (34.
8% globally), and about 95% of them are ASCVD.
Only 1.
5% of ASCVD patients are prescribed GLP-1RA and 5.
4% are prescribed SGLT-2i
.

About the reasons for this phenomenon, Professor Holst said: "The impact of higher prices is a common cause of SGLT-2i and GLP-1RA-utilized, genital infections caused by SGLT-2i, though not serious, but patients also difficult to accept
.

Phase Compared with SGLT-2i, I know more about the clinical application of GLP-1RA.
In the past, we underestimated the impact of injections on the clinical application of drugs.
Compared with oral drugs, doctors and patients are less willing to use injections.
Perhaps it is the reason for the low clinical use rate of GLP-1.
If GLP-1RA is changed to oral tablets, its clinical use rate may be higher
.

"The 2020 version of the "China Type 2 Diabetes Prevention Guidelines" recommended that combined ASCVD or cardiovascular High-risk T2DM patients, regardless of whether their HbA1c meets the standard, should be added to metformin with GLP-1RA or SGLT-2i with evidence of ASCVD benefit (recommended level A) as long as there is no contraindication
.

Professor Xiao said: "Currently, the use rate of GLP-1RA and SGLT-2i in China is very low.
This is contrary to the principles recommended by the guidelines.
It is a problem worthy of our deep consideration and attention, because the purpose of diabetes treatment is to reduce complications.
, Especially for cardiovascular complications
.

Only effective interventions on the multiple cardiovascular risk factors of diabetes and the use of drugs with definite benefits for the cardiovascular system can greatly reduce the risk of cardiovascular death in patients with T2DM and improve the quality of life of patients
.

To achieve this goal, it is also necessary to strengthen health education for diabetic patients and pass the latest knowledge and ideas to patients
.

"GLA: Hypoglycemic drugs Figure 3 The use rate of SGLT-2i and GLP-1RA is not high regardless of whether patients have CVD or not.
Summary The brilliant 81st American Diabetes Association (ADA) annual meeting has come to an end.
Fortunately, I interviewed Professor Jens Juul Holst, winner of the Banting Scientific Achievement Award, and Professor Xiao Xinhua of Peking Union Medical College Hospital, to comment on some of the key and hot topics from different aspects of China and the West
.

Regarding the clinical application of hypoglycemic drugs with cardiovascular protection, The two professors both proposed that with the accumulation of evidence-based evidence, studies have confirmed that SGLT-2i has dual protective effects on the heart and kidneys, and the cardioprotective effects of GLP-1RA have also been confirmed, but the clinical effects of these two types of drugs The utilization rate is not high.
In the future, it is necessary to strengthen health promotion and education, increase the clinical use rate of these two types of drugs, and reduce the risk of death and disability from diabetes
.
The
source of this articleidiabetes chief editorCao Qian-End-"This article is only used for To provide scientific information to medical and health professionals, does not represent the position of the platform.
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