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Author: Medical team doctors report NMT NMT ENDO compile reports, please do not reprint without authorization.
Guide: On March 20th, US time (early morning on the 21st, Beijing time), the 2021 American Society of Endocrinology (ENDO) was officially held.
After the chairman of the conference finished his speech, the main venue ushered in a wonderful debate, the topic of which was "Should SGLT-2i be used for the treatment of T1DM".
Counter-party: Professor Anne Peters from the Keck School of Medicine of the University of Southern California, the core view is "The DKA risk of SGLT-2i is the main factor limiting its use in the treatment of T1DM, even if it is refined patient management, currently It is still unable to achieve effective control of this risk, and there is no evidence to help us screen out patients with T1DM who are safer using SGLT-2i.
Therefore, we should not promote the general use of SGLT-2i in the treatment of T1DM", in simple terms "DKA risk is uncontrollable", Professor Anne Peters shared the cases he received.
Pros: Professor Andrew J.
Ahmann from Oregon Health Sciences University.
He believes that insulin cannot fully meet the treatment needs of T1DM and brings many negative effects.
SGLT-2i can bring a variety of proven benefits, and It has potential benefits in cardiovascular disease prevention and kidney protection, which is very important for patients.
However, mentioning the risk of DKA does limit its usability.
At present, there is some evidence to help us reduce this risk, but more research is needed in the future to clarify the preventive measures of DKA and which patients with T1DM are safe to use SGLT-2i.
.
In short, Professor Andrew J.
Ahmann believes that “SGLT-2i has potential as an adjuvant therapy for insulin”.Left (opposing side): Professor Anne Peters, MD, Professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California, Director of the Clinical Diabetes Program of the University of Southern California, Chairman of the Committee of the Diabetes Device Endocrinology Society, member of the EASD/ADA Technical Safety Committee, former post On the right of the ADA committee (supporting party): Professor Andrew J.
Ahmann, Director of Harold Schnitzel Diabetes Health Center, Professor Anne Peters, Professor of Medicine at Oregon Health Sciences University: Oppose SGLT-2i for T1DM treatment, DKA risk is still high Uncontrollable The reason why SGLT-2i is not supported in T1DM patients, Professor Anne Peters mentioned the following reasons: 1.
Increase the risk of DKA; 2.
No matter how well prepared, the risk of DKA still exists; 3.
In low socioeconomic status (SES) In patients, the risk of DKA is particularly higher; 4.
The benefit of A1c reduction is relatively small; 5.
The benefit of weight loss is relatively small; 6.
The occurrence of hypoglycemia is not reduced; 7.
In general, the clinician is in It may be worse than clinical trials to reduce the risk of DKA; 8.
FDA does not support it.
Professor Anne Peters believes that “the risk of DKA is not yet controllable” is the main limiting factor.
In 2015, as the first author, Professor Anne Peters and colleagues published an article titled “Diabetic ketoacids of orthoglycemia and blood sugar” in Diabetes Cares.
Poisoning (euDKA): Potential Complications of SGLT-2i Therapy" article describes the risk of euDKA during the use of SGLT-2i.
In multiple clinical trials, SGLT-2i also showed a significant increase in the risk of DKA.
Table 1 The incidence of DKA in DEPICT-2, EASE-2/3 and inTandem3 tests Note: Different tests have different judgment criteria for DKA and cannot be directly compared.
In clinical practice, Professor Anne Peters will also prescribe SGLT-2i to some T1DM patients, but he is very cautious: ➤Ensure that patients are well educated; ➤In patient education, special emphasis will be placed on avoiding DKA as much as possible, and provide handouts and procedures.
Materials required for ketone body testing. Patients will be asked to perform multiple ketone tests 2 weeks before the start of SGLT-2i to familiarize themselves with the ketone test process; ➤Start from a low dose and gradually increase; ➤Standby around the clock so that the patient can contact at any time.
Even so, there are still patients treated with SGLT-2i who are hospitalized due to SGLT-2i-related DKA.
Sharing of cases-Even with refined management, DKA risks still exist.
Professor Anne Peters shared with us a case received in person.
A patient with T1DM, upon request of the patient, added canagliflozin (to Starting at 100mg/d), blood sugar control is improved.
Figure 1 Blood glucose control 1.
About 1 year after the first hospitalization due to DKA, the patient arbitrarily increased the dose to 300 mg/d despite the risk of euDKA, due to lack of carbohydrate (CHO) intake and insulin dosage Decrease, first hospitalization due to euDKA.
Received treatment and improved after stopping canagliflozin.
Then, canagliflozin 100mg/d was reactivated, and ketone body levels were monitored daily for the next four years.
Figure 2 Monitoring situation 2.
Re-admission for DKA The patient was monitored for serum ketone bodies every morning.
However, during a flight, the insulin pump line was accidentally disconnected, and the ketone body level rose to 5.
0.
After the plane landed, the patient experienced vomiting and his blood sugar level was about 150 mg/dl.
Immediately he went to a local hospital for treatment and communicated on the phone.
Professor Anne Peters advised him to drink fruit juice, eat 30 grams of carbohydrates, and inject insulin.
With the improvement of the ketone body level, the patient fell asleep after replacing the insulin pump infusion set.
But that night, the insulin infusion set was set incorrectly, and insulin was injected.
The patient woke up with vomiting with a blood sugar level of 120 mg/dL and a serum ketone level of 6.
Immediately sent to the emergency room for treatment and admitted to the ICU.
The doctor gave insulin and D51/2ns (rate of 75cc/h) intravenous infusion.
As the blood sugar level drops, the insulin intravenous infusion slows down. Post-mortem analysis: Although the initial treatment helped the patient lower the anion gap (AG), the decrease in insulin infusion led to a widening of the AG.
The patient felt hungry but did not vomit.
The administration of food and insulin injections reduced the AG.
However, a few hours later, due to not eating enough carbohydrates and insulin intake, the patient had DKA again.
In the ICU, the patient received glucose and insulin infusions.
The DKA problem resolved, and he was discharged from the hospital.
Professor Anne Peters concluded: Although patients with T1DM may want to use SGLT-2i, it is still impossible to reduce the risk of DKA to an acceptable level, even in patients with very high education; on the contrary, if the patient lacks relevant recognition Knowing and executing, what will happen is unknown.
Therefore, it can only be said that SGLT-2i is used in the treatment of T1DM, and there is a chance in patients with high education and good compliance.
However, for the treatment of T1DM, the more likely recommendations than SGLT-2i are: ➤Use hybrid closed-loop technology to deliver insulin; ➤In T1D patients with ASCVD and/or CKD, the use of GLP-1RA can lead to weight loss and cardiovascular disease And possible kidney benefits.
Professor Andrew J.
Ahmann: There are many shortcomings in the current treatment of T1DM.
SGLT-2i can bring many benefits.
As an adjuvant therapy for insulin, it has potential.
Professor Andrew J.
Ahmann believes that there are many shortcomings in the current treatment of T1DM.
1.
Limitation of treatment methods Insulin is currently the only effective treatment drug, but as the course of the disease increases, blood sugar control becomes more difficult, and insulin causes weight gain, which in turn brings negative effects such as decreased compliance and increased cardiovascular risk factors. Figure 3 With the prolonged course of T1DM, blood sugar control becomes more and more difficult (Foster NC et al.
DIT 2019;21:66-72) 2.
The overall control is not satisfactory-little progress has been made in preventing ESRD, and patients with T1DM suffer from cardiovascular disease The risk of disease is still very high.
Studies have found that the incidence of acute cerebral infarction, stroke, amputation, and mortality in hyperglycemic crisis among the complications of diabetes has decreased significantly, but the decrease in ESRD is not significant.
The risk of ESRD in the DM population is 6.
1 times that of the general population.
Figure 4 Changes in the incidence of diabetes-related complications (Gregg EW et al.
N Engl J Med 2014;370:514-523) In addition, studies have ranked the risk factors for CVD in patients with T1DM: it was found that proteinuria/eGFR is the risk of T1DM The biggest risk factor for CVD, so effectively slowing down the decline in renal function is also important for the prevention of CVD.
Table 2 Ranking of CVD risk factors in T1DM patients (Rawshani A et al.
Circulation 2019:139:1900) 3.
SGLT-2i used in T1DM treatment can bring multiple benefits such as lowering HbA1c (about 0.
4% reduction) without increasing low Blood sugar risk; weight reduction (by about 3%-4%); lower insulin dose (by about 10%); improvement of blood glucose fluctuations; and it has the potential benefits of improving kidney outcomes and improving CV outcomes, and can improve quality of life (QOL).
4.
SGLT-2i-related DKA risk factors Professor Andrew J.
Ahmann mentioned that the main side effects of SGLT-2i include DKA, genital fungal infections and urinary tract infections.
DKA is undoubtedly the point of most concern.
Attention should be paid to avoid the following DKA risk factors: ➤General factors: such as past history of DKA, elevated HbA1c, poor compliance, alcohol or drug abuse, mental illness, younger age (adolescent), female.
➤Specific factors: drastically reduced insulin dose, reduced carbohydrate intake, dehydration, BMI<25kg/m^2, use of insulin pump.
5.
Potential methods for the safe use of SGLT-2i in T1DM Professor Andrew J.
Ahmann believes that in the safe use of SGLT-2i in the treatment of T1DM, first attention should be paid to screening suitable patients: The United Kingdom (NICE) approved the use of SGLT in the following T1DM populations -2i: ➤BMI ≥27kg/m^2; ➤poor blood sugar control; ➤Prescription can only be made under the premise of patient education, including: informing DKA risks, DKA identification, when and how to monitor ketone levels and how response.
Secondly, adequate patient education should be carried out.
Studies have found that structured patient education can reduce the risk of DKA in TIDM patients by 30%-70%, and SGLT-2i should be discontinued in high-risk situations.
6.
Once DKA appears, what is the treatment strategy? Stop SGLT-2i, inject insulin (according to the I:C ratio), take carbohydrates (30g), and give fluids.
Finally, Professor Andrew J.
Ahmann concluded: ➤SGLT-2i can bring a variety of proven benefits to patients with T1DM; ➤SGLT-2i has multiple potential benefits in cardiovascular disease and renal protection, which is for patients It may be very important; ➤DKA risk limits its availability; ➤There is not enough research to clarify the preventive measures of DKA and which T1DM patients are safe to use SGLT-2i; ➤We should continue to study SGLT-2i as an insulin aid Potential for treatment.
Guide: On March 20th, US time (early morning on the 21st, Beijing time), the 2021 American Society of Endocrinology (ENDO) was officially held.
After the chairman of the conference finished his speech, the main venue ushered in a wonderful debate, the topic of which was "Should SGLT-2i be used for the treatment of T1DM".
Counter-party: Professor Anne Peters from the Keck School of Medicine of the University of Southern California, the core view is "The DKA risk of SGLT-2i is the main factor limiting its use in the treatment of T1DM, even if it is refined patient management, currently It is still unable to achieve effective control of this risk, and there is no evidence to help us screen out patients with T1DM who are safer using SGLT-2i.
Therefore, we should not promote the general use of SGLT-2i in the treatment of T1DM", in simple terms "DKA risk is uncontrollable", Professor Anne Peters shared the cases he received.
Pros: Professor Andrew J.
Ahmann from Oregon Health Sciences University.
He believes that insulin cannot fully meet the treatment needs of T1DM and brings many negative effects.
SGLT-2i can bring a variety of proven benefits, and It has potential benefits in cardiovascular disease prevention and kidney protection, which is very important for patients.
However, mentioning the risk of DKA does limit its usability.
At present, there is some evidence to help us reduce this risk, but more research is needed in the future to clarify the preventive measures of DKA and which patients with T1DM are safe to use SGLT-2i.
.
In short, Professor Andrew J.
Ahmann believes that “SGLT-2i has potential as an adjuvant therapy for insulin”.Left (opposing side): Professor Anne Peters, MD, Professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California, Director of the Clinical Diabetes Program of the University of Southern California, Chairman of the Committee of the Diabetes Device Endocrinology Society, member of the EASD/ADA Technical Safety Committee, former post On the right of the ADA committee (supporting party): Professor Andrew J.
Ahmann, Director of Harold Schnitzel Diabetes Health Center, Professor Anne Peters, Professor of Medicine at Oregon Health Sciences University: Oppose SGLT-2i for T1DM treatment, DKA risk is still high Uncontrollable The reason why SGLT-2i is not supported in T1DM patients, Professor Anne Peters mentioned the following reasons: 1.
Increase the risk of DKA; 2.
No matter how well prepared, the risk of DKA still exists; 3.
In low socioeconomic status (SES) In patients, the risk of DKA is particularly higher; 4.
The benefit of A1c reduction is relatively small; 5.
The benefit of weight loss is relatively small; 6.
The occurrence of hypoglycemia is not reduced; 7.
In general, the clinician is in It may be worse than clinical trials to reduce the risk of DKA; 8.
FDA does not support it.
Professor Anne Peters believes that “the risk of DKA is not yet controllable” is the main limiting factor.
In 2015, as the first author, Professor Anne Peters and colleagues published an article titled “Diabetic ketoacids of orthoglycemia and blood sugar” in Diabetes Cares.
Poisoning (euDKA): Potential Complications of SGLT-2i Therapy" article describes the risk of euDKA during the use of SGLT-2i.
In multiple clinical trials, SGLT-2i also showed a significant increase in the risk of DKA.
Table 1 The incidence of DKA in DEPICT-2, EASE-2/3 and inTandem3 tests Note: Different tests have different judgment criteria for DKA and cannot be directly compared.
In clinical practice, Professor Anne Peters will also prescribe SGLT-2i to some T1DM patients, but he is very cautious: ➤Ensure that patients are well educated; ➤In patient education, special emphasis will be placed on avoiding DKA as much as possible, and provide handouts and procedures.
Materials required for ketone body testing. Patients will be asked to perform multiple ketone tests 2 weeks before the start of SGLT-2i to familiarize themselves with the ketone test process; ➤Start from a low dose and gradually increase; ➤Standby around the clock so that the patient can contact at any time.
Even so, there are still patients treated with SGLT-2i who are hospitalized due to SGLT-2i-related DKA.
Sharing of cases-Even with refined management, DKA risks still exist.
Professor Anne Peters shared with us a case received in person.
A patient with T1DM, upon request of the patient, added canagliflozin (to Starting at 100mg/d), blood sugar control is improved.
Figure 1 Blood glucose control 1.
About 1 year after the first hospitalization due to DKA, the patient arbitrarily increased the dose to 300 mg/d despite the risk of euDKA, due to lack of carbohydrate (CHO) intake and insulin dosage Decrease, first hospitalization due to euDKA.
Received treatment and improved after stopping canagliflozin.
Then, canagliflozin 100mg/d was reactivated, and ketone body levels were monitored daily for the next four years.
Figure 2 Monitoring situation 2.
Re-admission for DKA The patient was monitored for serum ketone bodies every morning.
However, during a flight, the insulin pump line was accidentally disconnected, and the ketone body level rose to 5.
0.
After the plane landed, the patient experienced vomiting and his blood sugar level was about 150 mg/dl.
Immediately he went to a local hospital for treatment and communicated on the phone.
Professor Anne Peters advised him to drink fruit juice, eat 30 grams of carbohydrates, and inject insulin.
With the improvement of the ketone body level, the patient fell asleep after replacing the insulin pump infusion set.
But that night, the insulin infusion set was set incorrectly, and insulin was injected.
The patient woke up with vomiting with a blood sugar level of 120 mg/dL and a serum ketone level of 6.
Immediately sent to the emergency room for treatment and admitted to the ICU.
The doctor gave insulin and D51/2ns (rate of 75cc/h) intravenous infusion.
As the blood sugar level drops, the insulin intravenous infusion slows down. Post-mortem analysis: Although the initial treatment helped the patient lower the anion gap (AG), the decrease in insulin infusion led to a widening of the AG.
The patient felt hungry but did not vomit.
The administration of food and insulin injections reduced the AG.
However, a few hours later, due to not eating enough carbohydrates and insulin intake, the patient had DKA again.
In the ICU, the patient received glucose and insulin infusions.
The DKA problem resolved, and he was discharged from the hospital.
Professor Anne Peters concluded: Although patients with T1DM may want to use SGLT-2i, it is still impossible to reduce the risk of DKA to an acceptable level, even in patients with very high education; on the contrary, if the patient lacks relevant recognition Knowing and executing, what will happen is unknown.
Therefore, it can only be said that SGLT-2i is used in the treatment of T1DM, and there is a chance in patients with high education and good compliance.
However, for the treatment of T1DM, the more likely recommendations than SGLT-2i are: ➤Use hybrid closed-loop technology to deliver insulin; ➤In T1D patients with ASCVD and/or CKD, the use of GLP-1RA can lead to weight loss and cardiovascular disease And possible kidney benefits.
Professor Andrew J.
Ahmann: There are many shortcomings in the current treatment of T1DM.
SGLT-2i can bring many benefits.
As an adjuvant therapy for insulin, it has potential.
Professor Andrew J.
Ahmann believes that there are many shortcomings in the current treatment of T1DM.
1.
Limitation of treatment methods Insulin is currently the only effective treatment drug, but as the course of the disease increases, blood sugar control becomes more difficult, and insulin causes weight gain, which in turn brings negative effects such as decreased compliance and increased cardiovascular risk factors. Figure 3 With the prolonged course of T1DM, blood sugar control becomes more and more difficult (Foster NC et al.
DIT 2019;21:66-72) 2.
The overall control is not satisfactory-little progress has been made in preventing ESRD, and patients with T1DM suffer from cardiovascular disease The risk of disease is still very high.
Studies have found that the incidence of acute cerebral infarction, stroke, amputation, and mortality in hyperglycemic crisis among the complications of diabetes has decreased significantly, but the decrease in ESRD is not significant.
The risk of ESRD in the DM population is 6.
1 times that of the general population.
Figure 4 Changes in the incidence of diabetes-related complications (Gregg EW et al.
N Engl J Med 2014;370:514-523) In addition, studies have ranked the risk factors for CVD in patients with T1DM: it was found that proteinuria/eGFR is the risk of T1DM The biggest risk factor for CVD, so effectively slowing down the decline in renal function is also important for the prevention of CVD.
Table 2 Ranking of CVD risk factors in T1DM patients (Rawshani A et al.
Circulation 2019:139:1900) 3.
SGLT-2i used in T1DM treatment can bring multiple benefits such as lowering HbA1c (about 0.
4% reduction) without increasing low Blood sugar risk; weight reduction (by about 3%-4%); lower insulin dose (by about 10%); improvement of blood glucose fluctuations; and it has the potential benefits of improving kidney outcomes and improving CV outcomes, and can improve quality of life (QOL).
4.
SGLT-2i-related DKA risk factors Professor Andrew J.
Ahmann mentioned that the main side effects of SGLT-2i include DKA, genital fungal infections and urinary tract infections.
DKA is undoubtedly the point of most concern.
Attention should be paid to avoid the following DKA risk factors: ➤General factors: such as past history of DKA, elevated HbA1c, poor compliance, alcohol or drug abuse, mental illness, younger age (adolescent), female.
➤Specific factors: drastically reduced insulin dose, reduced carbohydrate intake, dehydration, BMI<25kg/m^2, use of insulin pump.
5.
Potential methods for the safe use of SGLT-2i in T1DM Professor Andrew J.
Ahmann believes that in the safe use of SGLT-2i in the treatment of T1DM, first attention should be paid to screening suitable patients: The United Kingdom (NICE) approved the use of SGLT in the following T1DM populations -2i: ➤BMI ≥27kg/m^2; ➤poor blood sugar control; ➤Prescription can only be made under the premise of patient education, including: informing DKA risks, DKA identification, when and how to monitor ketone levels and how response.
Secondly, adequate patient education should be carried out.
Studies have found that structured patient education can reduce the risk of DKA in TIDM patients by 30%-70%, and SGLT-2i should be discontinued in high-risk situations.
6.
Once DKA appears, what is the treatment strategy? Stop SGLT-2i, inject insulin (according to the I:C ratio), take carbohydrates (30g), and give fluids.
Finally, Professor Andrew J.
Ahmann concluded: ➤SGLT-2i can bring a variety of proven benefits to patients with T1DM; ➤SGLT-2i has multiple potential benefits in cardiovascular disease and renal protection, which is for patients It may be very important; ➤DKA risk limits its availability; ➤There is not enough research to clarify the preventive measures of DKA and which T1DM patients are safe to use SGLT-2i; ➤We should continue to study SGLT-2i as an insulin aid Potential for treatment.
