Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes

Sohee Park; Han Eol Jeong; Sungho Bea; Oriana H Y Yu; Young Min Cho; Seng Chan You; Kenneth K C Man; Ju-Young Shin

doi:10.1111/dom.15221

Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes

Sohee Park, Han Eol Jeong, Sungho Bea, Oriana H Y Yu, Young Min Cho, Seng Chan You, Kenneth K C Man, Ju-Young Shin

Research output: Contribution to journal › Article › peer-review

Abstract

AIM: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU).

MATERIALS AND METHODS: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models.

RESULTS: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses.

CONCLUSIONS: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.

Original language	English
Pages (from-to)	3248-3258
Number of pages	11
Journal	Diabetes, Obesity and Metabolism
Volume	25
Issue number	11
Early online date	28 Jul 2023
DOIs	https://doi.org/10.1111/dom.15221
Publication status	Published - 1 Nov 2023

Bibliographical note

Data Access Statement

The data that support the findings of this study are available from the Health Insurance Review and Assessment Service of South Korea but restrictions apply to the availability of these data due to domestic laws and regulations that prohibit the distribution or release of individual's data to the public, and so are not publicly available. Data are however available from the authors upon reasonable request and with permis- sion of the Health Insurance Review and Assessment Service of South Korea.

Keywords

Humans
Diabetes Mellitus, Type 2/complications
Sodium-Glucose Transporter 2 Inhibitors/adverse effects
Cardiovascular Diseases/complications
Cohort Studies
Diuretics
Risk Factors
Dipeptidyl-Peptidase IV Inhibitors/adverse effects
Amputation, Surgical
Symporters
Glucose
Sodium
Hypoglycemic Agents

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10.1111/dom.15221

Cite this

@article{61c9e1e1c2de4c5b897c49d6812c7ccb,

title = "Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes",

abstract = "AIM: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU).MATERIALS AND METHODS: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models.RESULTS: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses.CONCLUSIONS: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.",

keywords = "Humans, Diabetes Mellitus, Type 2/complications, Sodium-Glucose Transporter 2 Inhibitors/adverse effects, Cardiovascular Diseases/complications, Cohort Studies, Diuretics, Risk Factors, Dipeptidyl-Peptidase IV Inhibitors/adverse effects, Amputation, Surgical, Symporters, Glucose, Sodium, Hypoglycemic Agents",

author = "Sohee Park and Jeong, {Han Eol} and Sungho Bea and Yu, {Oriana H Y} and Cho, {Young Min} and You, {Seng Chan} and Man, {Kenneth K C} and Ju-Young Shin",

note = "{\textcopyright} 2023 John Wiley & Sons Ltd.",

year = "2023",

month = nov,

day = "1",

doi = "10.1111/dom.15221",

language = "English",

volume = "25",

pages = "3248--3258",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell",

number = "11",

}

Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes. / Park, Sohee; Jeong, Han Eol; Bea, Sungho et al.
In: Diabetes, Obesity and Metabolism, Vol. 25, No. 11, 01.11.2023, p. 3248-3258.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes

AU - Park, Sohee

AU - Jeong, Han Eol

AU - Bea, Sungho

AU - Yu, Oriana H Y

AU - Cho, Young Min

AU - You, Seng Chan

AU - Man, Kenneth K C

AU - Shin, Ju-Young

PY - 2023/11/1

Y1 - 2023/11/1

N2 - AIM: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU).MATERIALS AND METHODS: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models.RESULTS: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses.CONCLUSIONS: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.

AB - AIM: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU).MATERIALS AND METHODS: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models.RESULTS: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses.CONCLUSIONS: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.

KW - Humans

KW - Diabetes Mellitus, Type 2/complications

KW - Sodium-Glucose Transporter 2 Inhibitors/adverse effects

KW - Cardiovascular Diseases/complications

KW - Cohort Studies

KW - Diuretics

KW - Risk Factors

KW - Dipeptidyl-Peptidase IV Inhibitors/adverse effects

KW - Amputation, Surgical

KW - Symporters

KW - Glucose

KW - Sodium

KW - Hypoglycemic Agents

UR - https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.15221

U2 - 10.1111/dom.15221

DO - 10.1111/dom.15221

M3 - Article

C2 - 37503763

SN - 1462-8902

VL - 25

SP - 3248

EP - 3258

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 11

ER -

Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes

Abstract

Bibliographical note

Data Access Statement

Keywords

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