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Yimaitong compiles and organizes, please do not reprint without authorization
.
Guide: Recently, a new practice guide jointly formulated by an international expert group-"Adults with Type 2 Diabetes Application SGLT-2i/GLP-1RA: Clinical Practice Guidelines" was released in the British Medical Journal (IF: 30.
223)
.
The guideline puts forward the concept of "stratifying patients according to cardiovascular risk factors and making differentiated recommendations for SGLT-2i and GLP-1RA"
.
It also answered the "Five Questions Related to the Clinical Use of SGLT-2i/GLP-1RA"
.
Are you confused about the use of SGLT-2i/GLP-1RA? The text may have the answer you want
.
➤Question 1: (Core of the guideline) How to stratify patients and make differentiated recommendations for SGLT-2i and GLP-1RA? ➤Question 2: When prescribing SGLT-2i and GLP-1RA, do I need to consider HbA1c and blood sugar levels? ➤Question 3: What are the adverse reactions related to SGLT-2i and GLP-1RA, and what are the coping strategies? ➤Question 4: Prescription SGLT-2i and GLP-1RA, what practical problems may be encountered? ➤Question 5: Regarding SGLT-2i and GLP-1RA, what are the current issues to be resolved? Question 1: (Guideline core) How to stratify patients and make differentiated recommendations for SGLT-2i/GLP-1RA? "Risk stratification of patients and differentiated recommendation of SGLT-2i/GLP-1RA" is the core of this guide, but it should be emphasized that this guide aims to help manage the long-term complications of T2DM and does not focus on short-term blood glucose management ：Drug differentiation recommendation ➤Patients with ≤3 cardiovascular risk factors and not accompanied by cardiovascular disease or chronic kidney disease: It is not recommended to start SGLT-2i or GLP-1RA
.
(Weak recommendation) ➤Patients with more than 3 cardiovascular risk factors and no CVD or CKD: It is recommended to start SGLT-2i, and GLP-1RA is not recommended
.
(Weak recommendation) ➤Patients with CVD or CKD: It is recommended to start SGLT-2i and GLP-1RA
.
(Weak recommendation) ➤Patients with CVD and CKD: SGLT-2i is strongly recommended, and GLP-1RA is weakly recommended (as an alternative)
.
➤For patients who aim to further improve the outcome of CVD and CKD: SGLT-2i is more recommended than GLP-1RA (weak recommendation)
.
Related explanations: Cardiovascular risk factors: including but not limited to age> 60 years old, male, ethnicity (Asian, African or Hispanic), family history of cardiovascular or kidney disease, poor HbA1c control (≥6.
5%), Smoking, poor hypertension control (>140/90mmHg), dyslipidemia [including elevated total cholesterol (≥5.
2mmol/L) or low high-density lipoprotein cholesterol (<1mmol/L)]
.
Cardiovascular disease definition: suffering from coronary artery disease (diagnosed by diagnostic tests or previous myocardial infarction) or stroke
.
Definition of chronic kidney disease: eGFR<60mL/min/1.
73m^2 or with proteinuria (24-hour urine protein excretion rate ≥30mg/24h or urine albumin-creatinine ratio ≥30mg/g)
.
Figure 1 Recommendations for the classification of SGLT-2i and GLP-1RA Question 2: When prescribing SGLT-2i and GLP-1RA, do I need to consider HbA1c and blood glucose levels? For a long time, HbA1c has been used to guide clinical decision-making in T2DM
.
However, systematic reviews show that the benefits of HbA1c normalization are minimal
.
In addition, the protective effects of SGLT-2i and GLP-1RA on the cardiovascular and kidneys have nothing to do with HbA1c levels
.
Therefore, cardiovascular and renal risks constitute possible indications for the two types of drugs
.
However, given that relevant studies are conducted in patients with HbA1c>6.
5%, it is uncertain whether patients with lower HbA1c levels can obtain the same benefits
.
How to treat severe hyperglycemia is not within the guidance of this guide
.
It should be noted that patients with very high blood glucose levels (such as> 16.
7 mmol/L or HbA1c> 9%) may have severe, life-threatening hyperglycemia, accompanied by volume reduction, severe infection and possible ketoacidosis.
Special assessments and optimized care are needed for these patients, which are covered in other clinical practice guidelines
.
When making decisions, clinicians should also consider the risk of other chronic complications in patients with high HbA1c levels, such as retinopathy, cataracts, neuropathy, and diabetic foot ulcers
.
Question 3: What are the adverse reactions related to SGLT-2i and GLP-1RA, and what are the coping strategies? The safety of the two types of drugs is widely recognized, but the following adverse events and potential hazards are still possible: 1.
GLP-1RA and gastrointestinal adverse reactions include abdominal pain, nausea, vomiting and diarrhea, which may be serious or even cause discontinuation.
Medicine
.
Countermeasures: When starting GLP-1RA, the method of "starting with a low dose and gradually increasing the dose" should be adopted
.
If symptoms occur, it is recommended to maintain the dose or increase the dose at a slower rate
.
2.
SGLT-2i and genital infections SGLT-2i has the risk of causing genital infections (such as female vaginitis and male balanitis)
.
A previous history of relevant medical conditions can greatly increase the risk (7 times for women and 11 times for men).
Fournier's gangrene is the most serious type of genital infection.
This disease is very rare but can be fatal
.
Countermeasures: Before prescribing SGLT-2i, the patient should be asked whether there is a history of genital infection
.
3.
A review of SGLT-2i and diabetic ketoacidosis raised concerns about diabetic ketoacidosis and the use of SGLT-2i, and unlike other diabetes drugs, there are reports that when the blood sugar of patients receiving SGLT-2i is normal When within the range, diabetic ketoacidosis may also occur
.
Countermeasures: Clinicians should assess the risk of ketoacidosis in patients.
Related factors include restricted diet, severe diarrhea, gastrointestinal surgery, very low carbohydrate diet, and excessive drinking
.
4.
Restrictions on the use of renal function FDA has not approved the use of SGLT-2i in people with eGFR<30ml/min/1.
73m^2.
The expert group believes that GLP-1RA may be more suitable for patients with advanced renal disease
.
5.
SGLT-2i and amputation In an observational study and CANVAS trial, the use of SGLT-2i was associated with an increased risk of amputation
.
However, follow-up related studies have reached inconsistent conclusions.
In this guide, the expert group took into account the low certainty of positive evidence and the very low incident rate, and did not describe it
.
6.
GLP-1RA and pancreatic cancer/pancreatitis patients and clinicians may be concerned that the use of GLP-1RA is associated with an increased risk of pancreatic cancer/pancreatitis, but this risk has not been reviewed by network meta-analysis (NMA) and other systematic reviews Confirmed
.
Question 4: When using SGLT-2i and GLP-1RA clinically, what are the actual problems that may be encountered? Regarding the use of SGLT-2i and GLP-1RA, this guide encourages doctors and patients to make joint decisions
.
When adding SGLT-2i or GLP-1RA, the existing medication regimen should be kept unchanged, unless there are contraindications or newly increased risks (such as hypoglycemia), for example: ➤GLP-1RA should not be used together with DPP-4i , That is, GLP-1RA should be used under the premise of discontinuing DPP-4i (Editor’s note: In an exclusive interview with Yimaitong, Professor Mu Yiming once answered this question-mainly for economic considerations, not drug safety Sex; see the original text: Heavy! "Clinical Expert Consensus on GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes" is released!)
.
➤Although neither SGLT-2i nor GLP-1RA increase the risk of hypoglycemia, doctors should consider whether other drugs that the patient is taking will increase the risk of hypoglycemia, especially in people at high risk of hypoglycemia or cardiovascular disease
.
➤If the blood glucose level is close to the target value, patients receiving insulin, sulfonylureas or glinide drugs may need to reduce the dose by 20%-50% or switch to a lower intensity treatment plan (such as reducing the number of medications)
.
Compliance problem of injection administration: Many patients do not like injection administration, but this is precisely the common route of administration of GLP-1RA, including: subcutaneous injection once a day (such as liraglutide and lixisenatide) or Twice a day (such as exenatide) and once a week (such as abiglutide, dulaglutide, exenatide microspheres and smeglutide)
.
At present, the US Food and Drug Administration and Health Canada have approved the marketing of oral smegaglutide, but it is not widely used in other countries
.
However, studies have shown that patients have significantly higher acceptance of GLP-1RA injected once a week
.
This also proves that it is important to discuss the dosing regimen with patients who are considering using GLP-1RA before prescribing
.
The following table summarizes the practical issues related to the use of SGLT-2I and GLP-1RA
.
Table 1 Problems that may be encountered in practical application of SGLT-2i and GLP-1RA Note: * Routine care includes life>
.
Question 5: Regarding SGLT-2i and GLP-1RA, what are the current issues to be resolved? Regarding SGLT-2i and GLP-1RA, the following issues still need to be resolved: ➤The additional benefits of SGLT-2i and GLP-1RA in combination are not yet clear; ➤Patients with chronic kidney disease with eGFR<30ml/min/1.
73m^2 The benefits and risks of using SGLT-2i are not yet clear; ➤The differences in key drug research results among patients of different races, ethnicities, and countries/regions need to be verified by tools
.
Yimaitong compiled and compiled from: Li S, Vandvik PO, Lytvyn L, et al.
SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline[J].
BMJ.
2021,373: n1091.
DOI: 10.
1136/bmj.
n1091.
.
Guide: Recently, a new practice guide jointly formulated by an international expert group-"Adults with Type 2 Diabetes Application SGLT-2i/GLP-1RA: Clinical Practice Guidelines" was released in the British Medical Journal (IF: 30.
223)
.
The guideline puts forward the concept of "stratifying patients according to cardiovascular risk factors and making differentiated recommendations for SGLT-2i and GLP-1RA"
.
It also answered the "Five Questions Related to the Clinical Use of SGLT-2i/GLP-1RA"
.
Are you confused about the use of SGLT-2i/GLP-1RA? The text may have the answer you want
.
➤Question 1: (Core of the guideline) How to stratify patients and make differentiated recommendations for SGLT-2i and GLP-1RA? ➤Question 2: When prescribing SGLT-2i and GLP-1RA, do I need to consider HbA1c and blood sugar levels? ➤Question 3: What are the adverse reactions related to SGLT-2i and GLP-1RA, and what are the coping strategies? ➤Question 4: Prescription SGLT-2i and GLP-1RA, what practical problems may be encountered? ➤Question 5: Regarding SGLT-2i and GLP-1RA, what are the current issues to be resolved? Question 1: (Guideline core) How to stratify patients and make differentiated recommendations for SGLT-2i/GLP-1RA? "Risk stratification of patients and differentiated recommendation of SGLT-2i/GLP-1RA" is the core of this guide, but it should be emphasized that this guide aims to help manage the long-term complications of T2DM and does not focus on short-term blood glucose management ：Drug differentiation recommendation ➤Patients with ≤3 cardiovascular risk factors and not accompanied by cardiovascular disease or chronic kidney disease: It is not recommended to start SGLT-2i or GLP-1RA
.
(Weak recommendation) ➤Patients with more than 3 cardiovascular risk factors and no CVD or CKD: It is recommended to start SGLT-2i, and GLP-1RA is not recommended
.
(Weak recommendation) ➤Patients with CVD or CKD: It is recommended to start SGLT-2i and GLP-1RA
.
(Weak recommendation) ➤Patients with CVD and CKD: SGLT-2i is strongly recommended, and GLP-1RA is weakly recommended (as an alternative)
.
➤For patients who aim to further improve the outcome of CVD and CKD: SGLT-2i is more recommended than GLP-1RA (weak recommendation)
.
Related explanations: Cardiovascular risk factors: including but not limited to age> 60 years old, male, ethnicity (Asian, African or Hispanic), family history of cardiovascular or kidney disease, poor HbA1c control (≥6.
5%), Smoking, poor hypertension control (>140/90mmHg), dyslipidemia [including elevated total cholesterol (≥5.
2mmol/L) or low high-density lipoprotein cholesterol (<1mmol/L)]
.
Cardiovascular disease definition: suffering from coronary artery disease (diagnosed by diagnostic tests or previous myocardial infarction) or stroke
.
Definition of chronic kidney disease: eGFR<60mL/min/1.
73m^2 or with proteinuria (24-hour urine protein excretion rate ≥30mg/24h or urine albumin-creatinine ratio ≥30mg/g)
.
Figure 1 Recommendations for the classification of SGLT-2i and GLP-1RA Question 2: When prescribing SGLT-2i and GLP-1RA, do I need to consider HbA1c and blood glucose levels? For a long time, HbA1c has been used to guide clinical decision-making in T2DM
.
However, systematic reviews show that the benefits of HbA1c normalization are minimal
.
In addition, the protective effects of SGLT-2i and GLP-1RA on the cardiovascular and kidneys have nothing to do with HbA1c levels
.
Therefore, cardiovascular and renal risks constitute possible indications for the two types of drugs
.
However, given that relevant studies are conducted in patients with HbA1c>6.
5%, it is uncertain whether patients with lower HbA1c levels can obtain the same benefits
.
How to treat severe hyperglycemia is not within the guidance of this guide
.
It should be noted that patients with very high blood glucose levels (such as> 16.
7 mmol/L or HbA1c> 9%) may have severe, life-threatening hyperglycemia, accompanied by volume reduction, severe infection and possible ketoacidosis.
Special assessments and optimized care are needed for these patients, which are covered in other clinical practice guidelines
.
When making decisions, clinicians should also consider the risk of other chronic complications in patients with high HbA1c levels, such as retinopathy, cataracts, neuropathy, and diabetic foot ulcers
.
Question 3: What are the adverse reactions related to SGLT-2i and GLP-1RA, and what are the coping strategies? The safety of the two types of drugs is widely recognized, but the following adverse events and potential hazards are still possible: 1.
GLP-1RA and gastrointestinal adverse reactions include abdominal pain, nausea, vomiting and diarrhea, which may be serious or even cause discontinuation.
Medicine
.
Countermeasures: When starting GLP-1RA, the method of "starting with a low dose and gradually increasing the dose" should be adopted
.
If symptoms occur, it is recommended to maintain the dose or increase the dose at a slower rate
.
2.
SGLT-2i and genital infections SGLT-2i has the risk of causing genital infections (such as female vaginitis and male balanitis)
.
A previous history of relevant medical conditions can greatly increase the risk (7 times for women and 11 times for men).
Fournier's gangrene is the most serious type of genital infection.
This disease is very rare but can be fatal
.
Countermeasures: Before prescribing SGLT-2i, the patient should be asked whether there is a history of genital infection
.
3.
A review of SGLT-2i and diabetic ketoacidosis raised concerns about diabetic ketoacidosis and the use of SGLT-2i, and unlike other diabetes drugs, there are reports that when the blood sugar of patients receiving SGLT-2i is normal When within the range, diabetic ketoacidosis may also occur
.
Countermeasures: Clinicians should assess the risk of ketoacidosis in patients.
Related factors include restricted diet, severe diarrhea, gastrointestinal surgery, very low carbohydrate diet, and excessive drinking
.
4.
Restrictions on the use of renal function FDA has not approved the use of SGLT-2i in people with eGFR<30ml/min/1.
73m^2.
The expert group believes that GLP-1RA may be more suitable for patients with advanced renal disease
.
5.
SGLT-2i and amputation In an observational study and CANVAS trial, the use of SGLT-2i was associated with an increased risk of amputation
.
However, follow-up related studies have reached inconsistent conclusions.
In this guide, the expert group took into account the low certainty of positive evidence and the very low incident rate, and did not describe it
.
6.
GLP-1RA and pancreatic cancer/pancreatitis patients and clinicians may be concerned that the use of GLP-1RA is associated with an increased risk of pancreatic cancer/pancreatitis, but this risk has not been reviewed by network meta-analysis (NMA) and other systematic reviews Confirmed
.
Question 4: When using SGLT-2i and GLP-1RA clinically, what are the actual problems that may be encountered? Regarding the use of SGLT-2i and GLP-1RA, this guide encourages doctors and patients to make joint decisions
.
When adding SGLT-2i or GLP-1RA, the existing medication regimen should be kept unchanged, unless there are contraindications or newly increased risks (such as hypoglycemia), for example: ➤GLP-1RA should not be used together with DPP-4i , That is, GLP-1RA should be used under the premise of discontinuing DPP-4i (Editor’s note: In an exclusive interview with Yimaitong, Professor Mu Yiming once answered this question-mainly for economic considerations, not drug safety Sex; see the original text: Heavy! "Clinical Expert Consensus on GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes" is released!)
.
➤Although neither SGLT-2i nor GLP-1RA increase the risk of hypoglycemia, doctors should consider whether other drugs that the patient is taking will increase the risk of hypoglycemia, especially in people at high risk of hypoglycemia or cardiovascular disease
.
➤If the blood glucose level is close to the target value, patients receiving insulin, sulfonylureas or glinide drugs may need to reduce the dose by 20%-50% or switch to a lower intensity treatment plan (such as reducing the number of medications)
.
Compliance problem of injection administration: Many patients do not like injection administration, but this is precisely the common route of administration of GLP-1RA, including: subcutaneous injection once a day (such as liraglutide and lixisenatide) or Twice a day (such as exenatide) and once a week (such as abiglutide, dulaglutide, exenatide microspheres and smeglutide)
.
At present, the US Food and Drug Administration and Health Canada have approved the marketing of oral smegaglutide, but it is not widely used in other countries
.
However, studies have shown that patients have significantly higher acceptance of GLP-1RA injected once a week
.
This also proves that it is important to discuss the dosing regimen with patients who are considering using GLP-1RA before prescribing
.
The following table summarizes the practical issues related to the use of SGLT-2I and GLP-1RA
.
Table 1 Problems that may be encountered in practical application of SGLT-2i and GLP-1RA Note: * Routine care includes life>
.
Question 5: Regarding SGLT-2i and GLP-1RA, what are the current issues to be resolved? Regarding SGLT-2i and GLP-1RA, the following issues still need to be resolved: ➤The additional benefits of SGLT-2i and GLP-1RA in combination are not yet clear; ➤Patients with chronic kidney disease with eGFR<30ml/min/1.
73m^2 The benefits and risks of using SGLT-2i are not yet clear; ➤The differences in key drug research results among patients of different races, ethnicities, and countries/regions need to be verified by tools
.
Yimaitong compiled and compiled from: Li S, Vandvik PO, Lytvyn L, et al.
SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline[J].
BMJ.
2021,373: n1091.
DOI: 10.
1136/bmj.
n1091.
