#SGLT2 inhibitor use and #dietary carbohydrate intake in Japanese individuals with type 2 diabetes: a randomized, open-label, 3-arm parallel comparative exploratory study
http://onlinelibrary.wiley.com/doi/10.1111/dom.12848/abstract
In conclusion, luseogliflozin has similar efficacy and safety in Japanese T2D individuals when meals contain 40-55% TEC, but a strict low-carbohydrate diet on this class of drug should be avoided to prevent SGLT2 inhibitor-associated diabetic ketoacidosis.
http://onlinelibrary.wiley.com/doi/10.1111/dom.12848/abstract
In conclusion, luseogliflozin has similar efficacy and safety in Japanese T2D individuals when meals contain 40-55% TEC, but a strict low-carbohydrate diet on this class of drug should be avoided to prevent SGLT2 inhibitor-associated diabetic ketoacidosis.
Wiley
SGLT2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: a randomized, open‐label, 3‐arm…
This study investigated safety and efficacy of the SGLT2 inhibitor luseogliflozin under differing carbohydrate intake in Japanese individuals with type 2 diabetes (T2D). Subjects were randomly assigned...
Risk of Diabetic #Ketoacidosis after Initiation of an #SGLT2 Inhibitor
http://www.nejm.org/doi/full/10.1056/NEJMc1701990
To the Editor:
Inhibitors of sodium–glucose cotransporter 2 (SGLT2) decrease plasma glucose by blocking the reabsorption of glucose at the proximal tubule.1,2 Case reports have suggested that SGLT2 inhibitors may be associated with an increased risk of diabetic ketoacidosis, which led to a warning from the Food and Drug Administration (FDA) in May 2015.3,4 The objective of our study was to assess the risk of diabetic ketoacidosis after the initiation of an SGLT2 inhibitor. We identified 50,220 patients who had received a new prescription for an SGLT2 inhibitor and 90,132 who had received a new prescription for a DPP4 inhibitor. Patients who were receiving SGLT2 inhibitors were younger and had fewer coexisting illnesses than those receiving DPP4 inhibitors but were more likely to receive insulin.
In conclusion, shortly after initiation, SGLT2 inhibitors were associated with approximately twice the risk of diabetic ketoacidosis as were DPP4 inhibitors, although cases of diabetic ketoacidosis leading to hospitalization were infrequent. The increased risk of diabetic ketoacidosis with SGLT2 inhibitors is among the factors to be considered at the time of prescribing and throughout therapy if patients present with symptoms suggestive of diabetic ketoacidosis.
http://www.nejm.org/doi/full/10.1056/NEJMc1701990
To the Editor:
Inhibitors of sodium–glucose cotransporter 2 (SGLT2) decrease plasma glucose by blocking the reabsorption of glucose at the proximal tubule.1,2 Case reports have suggested that SGLT2 inhibitors may be associated with an increased risk of diabetic ketoacidosis, which led to a warning from the Food and Drug Administration (FDA) in May 2015.3,4 The objective of our study was to assess the risk of diabetic ketoacidosis after the initiation of an SGLT2 inhibitor. We identified 50,220 patients who had received a new prescription for an SGLT2 inhibitor and 90,132 who had received a new prescription for a DPP4 inhibitor. Patients who were receiving SGLT2 inhibitors were younger and had fewer coexisting illnesses than those receiving DPP4 inhibitors but were more likely to receive insulin.
In conclusion, shortly after initiation, SGLT2 inhibitors were associated with approximately twice the risk of diabetic ketoacidosis as were DPP4 inhibitors, although cases of diabetic ketoacidosis leading to hospitalization were infrequent. The increased risk of diabetic ketoacidosis with SGLT2 inhibitors is among the factors to be considered at the time of prescribing and throughout therapy if patients present with symptoms suggestive of diabetic ketoacidosis.
New England Journal of Medicine
Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor | NEJM
Correspondence from The New England Journal of Medicine — Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor
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FDA warns about rare occurrences of a serious infection of the genital area with
#SGLT2 inhibitors for diabetes
https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm
[8-29-2018] The U.S. Food and Drug Administration (FDA) is warning that cases of a rare but serious infection of the genitals and area around the genitals have been reported with the class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as #Fournier’s gangrene. We are requiring a new warning about this risk to be added to the prescribing information of all SGLT2 inhibitors and to the patient Medication Guide.
Health care professionals should assess patients for Fournier’s gangrene if they present with the symptoms described above. If suspected, start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary. Discontinue the SGLT2 inhibitor, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the tissue under the skin that surrounds muscles, nerves, fat, and blood vessels of the perineum. The bacteria usually get into the body through a cut or break in the skin, where they quickly spread and destroy the tissue they infect. Having diabetes is a risk factor for developing Fournier’s gangrene; however, this condition is still rare among diabetic patients..
FDA warns about rare occurrences of a serious infection of the genital area with
#SGLT2 inhibitors for diabetes
https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm
[8-29-2018] The U.S. Food and Drug Administration (FDA) is warning that cases of a rare but serious infection of the genitals and area around the genitals have been reported with the class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as #Fournier’s gangrene. We are requiring a new warning about this risk to be added to the prescribing information of all SGLT2 inhibitors and to the patient Medication Guide.
Health care professionals should assess patients for Fournier’s gangrene if they present with the symptoms described above. If suspected, start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary. Discontinue the SGLT2 inhibitor, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the tissue under the skin that surrounds muscles, nerves, fat, and blood vessels of the perineum. The bacteria usually get into the body through a cut or break in the skin, where they quickly spread and destroy the tissue they infect. Having diabetes is a risk factor for developing Fournier’s gangrene; however, this condition is still rare among diabetic patients..
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Incidence and risk of vaginal #candidiasis associated with #SGLT2 inhibitors in real‐world practice for women with type 2 diabetes
https://onlinelibrary.wiley.com/doi/abs/10.1111/jdi.12912
Before starting SGLT2 inhibitors, 17 (14.9%) had positive vaginal Candida colonization. Younger age and presence of microangiopathy were significantly associated with the positive colonization in multivariate analysis. Among all subjects, 23 (20.2%, 8 by vaginitis and 15 by other reasons) discontinued SGLT2 inhibitors before reaching 6‐months test. Of 65 subjects who were negative for Candida at baseline and received 6‐months test, 24 (36.9%) converted to a positive culture, and multivariate analysis indicated older age as an independent risk for developing the Candida colonization. There were 18 (15.8%) subjects who developed symptomatic vaginitis, and they showed the similar characteristics to the 24 subjects. Most of those with negative cultures at 6‐months exhibited negative at 12‐months and vice versa.
Conclusions
The rates of developing positive colonization and symptomatic vaginitis after starting SGLT2 inhibitors appear to be higher in real‐world practice than the rates of 31% and 5‐10% in clinical trials, respectively. Risk factors of vaginal Candida colonization may be different before and after taking SGLT2 inhibitors.
Incidence and risk of vaginal #candidiasis associated with #SGLT2 inhibitors in real‐world practice for women with type 2 diabetes
https://onlinelibrary.wiley.com/doi/abs/10.1111/jdi.12912
Before starting SGLT2 inhibitors, 17 (14.9%) had positive vaginal Candida colonization. Younger age and presence of microangiopathy were significantly associated with the positive colonization in multivariate analysis. Among all subjects, 23 (20.2%, 8 by vaginitis and 15 by other reasons) discontinued SGLT2 inhibitors before reaching 6‐months test. Of 65 subjects who were negative for Candida at baseline and received 6‐months test, 24 (36.9%) converted to a positive culture, and multivariate analysis indicated older age as an independent risk for developing the Candida colonization. There were 18 (15.8%) subjects who developed symptomatic vaginitis, and they showed the similar characteristics to the 24 subjects. Most of those with negative cultures at 6‐months exhibited negative at 12‐months and vice versa.
Conclusions
The rates of developing positive colonization and symptomatic vaginitis after starting SGLT2 inhibitors appear to be higher in real‐world practice than the rates of 31% and 5‐10% in clinical trials, respectively. Risk factors of vaginal Candida colonization may be different before and after taking SGLT2 inhibitors.
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Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study
https://www.bmj.com/content/363/bmj.k4365
Use of #SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb #amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12).
Conclusions In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.
Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study
https://www.bmj.com/content/363/bmj.k4365
Use of #SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb #amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12).
Conclusions In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.
The BMJ
Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study
Objective To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern.
Design Register based cohort study.
Setting Sweden and Denmark from July 2013 to December 2016.…
Design Register based cohort study.
Setting Sweden and Denmark from July 2013 to December 2016.…
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#Fournier Gangrene Associated With Sodium–Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases
https://annals.org/aim/article-abstract/2732837/fournier-gangrene-associated-sodium-glucose-cotransporter-2-inhibitors-review-spontaneous
Use of sodium–glucose cotransporter-2 (#SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region.
The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4)...
Conclusion:
FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages
#Fournier Gangrene Associated With Sodium–Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases
https://annals.org/aim/article-abstract/2732837/fournier-gangrene-associated-sodium-glucose-cotransporter-2-inhibitors-review-spontaneous
Use of sodium–glucose cotransporter-2 (#SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region.
The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4)...
Conclusion:
FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages
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Assessing the Risk for #Gout With Sodium–Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Population-Based Cohort Study
Hyperuricemia is common in patients with type 2 diabetes mellitus and is known to cause gout. Sodium–glucose cotransporter-2 (#SGLT2) inhibitors prevent glucose reabsorption and lower serum uric acid levels..
..The gout incidence rate was lower among patients prescribed an SGLT2 inhibitor (4.9 events per 1000 person-years) than those prescribed a GLP1 agonist (7.8 events per 1000 person-years), with an HR of 0.64 (95% CI, 0.57 to 0.72) and a rate difference of −2.9 (CI, −3.6 to −2.1) per 1000 person-years.
Limitation:
Unmeasured confounding, missing data (namely incomplete laboratory data), and low baseline risk for gout.
Conclusion:
Adults with type 2 diabetes prescribed an SGLT2 inhibitor had a lower rate of gout than those prescribed a GLP1 agonist. Sodium–glucose cotransporter-2 inhibitors may reduce the risk for gout among adults with type 2 diabetes mellitus, although future studies are necessary to confirm this observation.
https://bit.ly/3a7MsMe
Assessing the Risk for #Gout With Sodium–Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Population-Based Cohort Study
Hyperuricemia is common in patients with type 2 diabetes mellitus and is known to cause gout. Sodium–glucose cotransporter-2 (#SGLT2) inhibitors prevent glucose reabsorption and lower serum uric acid levels..
..The gout incidence rate was lower among patients prescribed an SGLT2 inhibitor (4.9 events per 1000 person-years) than those prescribed a GLP1 agonist (7.8 events per 1000 person-years), with an HR of 0.64 (95% CI, 0.57 to 0.72) and a rate difference of −2.9 (CI, −3.6 to −2.1) per 1000 person-years.
Limitation:
Unmeasured confounding, missing data (namely incomplete laboratory data), and low baseline risk for gout.
Conclusion:
Adults with type 2 diabetes prescribed an SGLT2 inhibitor had a lower rate of gout than those prescribed a GLP1 agonist. Sodium–glucose cotransporter-2 inhibitors may reduce the risk for gout among adults with type 2 diabetes mellitus, although future studies are necessary to confirm this observation.
https://bit.ly/3a7MsMe
EUGLYCEMIC DIABETIC #KETOACIDOSIS WITH #COVID-19 INFECTION IN PATIENTS WITH TYPE 2 DIABETES TAKING #SGLT2 INHIBITORS
https://2medical.news/2021/01/23/euglycemic-diabetic-ketoacidosis-with-covid-19-infection-in-patients-with-type-2-diabetes-taking-sglt2-inhibitors/
Diabetes mellitus is associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Diabetic ketoacidosis (DKA) has also been reported to occur with this virus. A cluster of cases of euglycemic DKA (euDKA) was identified in patients with type 2 diabetes mellitus using sodium-glucose cotransporter-2 inhibitors (SGLT2is) who developed SARS-CoV-2 infection.. ..Five cases of euDKA, presenting with glucose levels <300 mg/dL, were …
https://2medical.news/2021/01/23/euglycemic-diabetic-ketoacidosis-with-covid-19-infection-in-patients-with-type-2-diabetes-taking-sglt2-inhibitors/
Diabetes mellitus is associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Diabetic ketoacidosis (DKA) has also been reported to occur with this virus. A cluster of cases of euglycemic DKA (euDKA) was identified in patients with type 2 diabetes mellitus using sodium-glucose cotransporter-2 inhibitors (SGLT2is) who developed SARS-CoV-2 infection.. ..Five cases of euDKA, presenting with glucose levels <300 mg/dL, were …