They are all incretin-type hypoglycemic drugs, with small differences but big differences

*It is only for medical professionals to read for reference.
There are many benefits for controlling sugar and protecting the heart.
In these cases, GLP-1RA is preferred
.

Secretin drugs have multiple physiological effects such as enhancing secretin, promoting insulin secretion, reducing glucagon production, reducing glycogen output, increasing glucose uptake in peripheral tissues, and enhancing the inhibitory response of the central nervous system to food intake.
Multiple versions of diabetes prevention and control guidelines such as the "China Type 2 Diabetes Prevention and Control Guidelines 2020 Edition" (hereinafter referred to as the 2020 "CDS Guidelines") are recommended for diabetes management [1]
.

Secretin drugs mainly include glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i)
.

What is the difference between the two? How to choose secretin drugs in the early management of diabetes? Both are incretin drugs, with different pharmacological mechanisms.
Under physiological conditions, glucagon-like peptide-1 (GLP-1) promotes insulin secretion and inhibits the secretion of glucagon in a glucose concentration-dependent manner, and stabilizes blood sugar.
It plays an important role in state regulation
.

The level of GLP-1 secretion in patients with type 2 diabetes (T2DM) was significantly reduced
.

Natural GLP-1 is rapidly decomposed and inactivated by dipeptidyl peptidase-4 (DPP-4) after secretion, and it needs continuous infusion to control blood sugar [2-3]
.

In order to make GLP-1 clinically applied, there are two feasible ways: one is to modify the structure to produce GLP-1 analogs, so that they are not easily decomposed by DPP-4, resulting in GLP-1RA, which represents the drug liraru Peptides, etc.
; the second is to inhibit DPP-4 enzyme activity, indirectly increase the activity of GLP-1, and then stimulate the release of insulin, reduce the secretion of glucagon, and thus produce DPP-4i, the representative drug is sitagliptin, etc.
[3]
.

Due to different mechanisms of action, the two drugs differ in the degree to which they can increase the concentration of GLP-1
.

GLP-1RA can increase the level of GLP-1 to reach the pharmacological concentration, while DPP-4i can only increase the level of GLP-1 within the physiological level [3]
.

At pharmacological concentrations, GLP-1RA can inhibit the level of glucagon and promote the production and release of insulin into the blood
.

In addition, it can suppress gastric emptying, reduce appetite, reduce the patient's intake and absorption of carbohydrates, and ultimately reduce blood sugar levels.
At the same time, it can reduce visceral and subcutaneous fat in patients with T2DM, and control weight
.

In addition, GLP-1RA has a certain effect of lowering blood pressure and regulating lipids [4]
.

 To compare effectiveness and safety, which one is used to increase the compliance rate? Both of the incretin drugs, GLP-1RA and DPP-4i are recommended by the guidelines in combination with metformin, which can help patients with T2DM to achieve early blood glucose management [1]
.

For T2DM patients without cardiovascular risk, the latest American Diabetes Association (ADA) guidelines recommend drug selection based on HbA1c and individual needs, so the efficacy and safety of hypoglycemic effects are important considerations [5]
.

 The LIRA-DPP-4 study is a head-to-head trial of GLP-1RA liraglutide and DPP-4i sitagliptin in European and American populations (Caucasian race)
.

The main body of the trial was conducted for a total of 26 weeks, followed by a 26-week extended study, and finally the sitagliptin treatment group was transferred to the liraglutide treatment group, followed by a further 26 weeks of follow-up, for a total of 78 weeks (Figure 1 )
.

   Figure 1 LIRA-DPP-4 and its extension study design A total of 658 T2DM patients from 13 countries were enrolled, and the efficacy of GLP-1RA drug liraglutide and DPP-4i drug sitagliptin was compared
.

The results showed that compared with sitagliptin, patients in the liraglutide group had a higher reduction in HbA1c, body weight and waist circumference (P<0.
0001), and the blood glucose compliance rate of patients in the liraglutide group at different doses was higher than that of sitagliptin The rate of achieving the composite endpoint of HbA1c<7%+no weight gain+no hypoglycemia was also significantly better than sitagliptin (P<0.
0001) (Figure 2)
.

The study also found that the higher the baseline HbA1c of patients in the liraglutide group, the greater the reduction in HbA1c after medication, and after the conversion of sitagliptin to liraglutide, the patient’s composite endpoint compliance rate further improved [6-8]
.

 Figure 2 LIRA-DPP-4 study: Liraglutide patients in each group had a higher blood glucose compliance rate than sitagliptin.
This study was also conducted in the Chinese population.
LIRA-DPP-4 CHINA is a multi-center, In an open, randomized, parallel controlled study, 368 patients with T2DM were randomly divided into groups based on previous metformin treatment at a ratio of 1:1, and combined with liraglutide 1.
8 mg or sitagliptin 100 mg for 26 weeks
.

The results showed that the HbA1c, FPG, and weight loss of patients treated with liraglutide were significantly better than those in the sitagliptin group (P<0.
0001), and more patients in the liraglutide group reached the composite endpoint, that is: more Of patients achieved HbA1c<7% without hypoglycemia and no weight gain (P<0.
0001) [9]
.

This suggests that liraglutide is significantly better than sitagliptin in terms of hypoglycemic effect and weight gain, which further confirms the efficacy and safety of GLP-1RA in Chinese patients with T2DM
.

Therefore, for T2DM patients without atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk factors, heart failure, chronic kidney disease (CKD), life>
.

In addition to sitagliptin, a randomized, open-label, parallel clinical study in China also found that after 24 weeks of treatment, the hypoglycemic effect of 1.
2 mg once daily subcutaneous injection of liraglutide in T2DM patients was significantly better than that of 5 mg per dose.
Saxagliptin once a day and 50 mg vildagliptin twice a day (P<0.
01) [10] (Figure 3)
.

 Figure 3 Liraglutide has significantly better efficacy in reducing HbA1c than saxagliptin and vildagliptin.
For T2DM patients with metformin combined with DPP-4i and whose blood sugar control is not up to standard, DPP-4i can be replaced with liraglutide.
For comprehensive management of patients
.

 Cardiovascular protection, the gap is further widened In China, 33.
9% of T2DM patients have cardiovascular disease, of which 94.
9% have ASCVD[11-12]
.

Reducing the risk of cardiovascular complications is one of the important goals of diabetes prevention and treatment in China
.

The results of multiple cardiovascular event outcome studies (CVOT) confirmed that some GLP-1RA drugs, such as liraglutide, have significant cardiovascular benefits and can reduce the occurrence of major adverse cardiovascular events (MACE) [13-16]
.

A large clinical trial LEADER study showed that the use of liraglutide on the basis of standard treatment can significantly reduce the risk of MACE (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) by 13%, and significantly reduce the risk of cardiovascular death by 22% and The risk of death from all causes is 15% [14]
.

 None of the CVOTs of DPP-4i drugs showed cardiovascular benefits, and their impact on MACE was uniformly neutral, that is, they only have cardiovascular safety without cardiovascular benefits [17-20]
.

For patients with ASCVD or high cardiovascular risk factors, the 2020 CDS Guidelines recommend that regardless of whether their HbA1c is up to standard, as long as there is no contraindication, GLP-1RA or sodium with clear evidence of cardiovascular benefit should be added to metformin- Glucose cotransporter 2 (SGLT-2) inhibitor [1]
.

On May 14, 2020, the State Drug Administration approved the cardiovascular indications of liraglutide, which is also China's first hypoglycemic drug with cardiovascular indications
.

Clinicians can follow the recommendations of the guidelines and drug instructions to select appropriate drugs for standardized treatment of patients, help more patients to achieve blood glucose standards, and improve the prognosis
.

 Conclusion Early effective management of T2DM can improve the long-term benefits of patients, and cardiovascular risk management is an important part of diabetes management
.

Both of the incretin drugs, GLP-1RA is better than DPP-4i in both hypoglycemic effectiveness and cardiovascular protection
.

The 2020 "CDS Guidelines" pointed out that regardless of whether HbA1c is up to standard, patients with ASCVD or T2DM with high-risk factors should use GLP-1RA hypoglycemic drugs with clear cardiovascular benefits such as liraglutide as soon as possible
.

For patients whose HbA1c is not up to standard in the treatment of metformin combined with DPP-4i, the hypoglycemic regimen of metformin combined with GLP-1RA can be considered, which not only has a strong hypoglycemic effect but also takes into account the safety of hypoglycemia and body weight, and better improves the prognosis and prognosis of diabetic patients.
Quality of life
.

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