Comparative Effectiveness of the Sodium–Glucose Cotransporter 2 Inhibitor Empagliflozin Versus Other Antihyperglycemics on Risk of Major Adverse Kidney Events

Abstract

OBJECTIVE To examine the comparative effectiveness of the sodium–glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin and other non-SGLT2i antihyperglycemics on the risk of major adverse kidney events (MAKE) of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease, or all-cause mortality. RESEARCH DESIGN AND METHODS In a cohort study of 379,033 new users of empagliflozin or other non-SGLT2i antihyperglycemics, predefined variables and covariates identified by a high-dimensional variable selection algorithm were used to build propensity scores. Weighted survival analyses were then applied to estimate the risk of MAKE. RESULTS Compared with other antihyperglycemics, empagliflozin use was associated with 0.99 (95% CI 0.51, 1.55) mL/min/1.73 m 2 less annual reduction in eGFR, 0.25 (95% CI 0.16, 0.33) kg/m 2 more annual decrease in BMI, and reduced risk of MAKE (hazard ratio [HR] 0.68 [95% CI 0.64, 0.73]). Empagliflozin use was associated with reduced risk of MAKE in eGFR ≥90, ≥60 to <90, ≥45 to <60, and ≥30 to <45 mL/min/1.73 m 2 (HR 0.70 [95% CI 0.60, 0.82], 0.66 [0.60, 0.73], 0.78 [0.69, 0.89]), and 0.71 [0.55, 0.92], respectively), in participants without albuminuria, with microalbuminuria and macroalbuminuria (HR 0.65 [95% CI 0.57, 0.75], 0.72 [0.66. 0.79], and 0.74 [0.62, 0.88], respectively), and in participants with and without cardiovascular disease (HR 0.67 [95% CI 0.61, 0.74] and 0.76 [0.69, 0.83], respectively). The association was evident in per-protocol analyses, which required continuation of the assigned antihyperglycemic medication (empagliflozin or other antihyperglycemics) during follow-up (HR 0.64 [95% CI 0.60, 0.70]), and in analyses requiring concurrent use of metformin in at least the first 90 days of follow-up (HR 0.63 [0.57–0.69]). CONCLUSIONS Among people with type 2 diabetes, empagliflozin use was associated with eGFR preservation, a greater decline in BMI, and a reduced risk of MAKE compared with other non-SGLT2i antihyperglycemics.

Temporal Trends in Incidence Rates of Lower Extremity Amputation and Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 to 2018

“…The clinical factors associated with LEA were selected based on previous studies. 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 Stages of CKD were determined using the mean level of outpatient estimated glomerular filtration rate (eGFR) in that year 40 : eGFR greater than or equal to 60 mL/min/1.73 m 2 was defined as no CKD, eGFR between 45 and 59 mL/min/1.73 m 2 was defined as CKD 3A, eGFR between 30 and 44 mL/min/1.73 m 2 was defined as CKD 3B, and eGFR between 15 and 29 mL/min/1.73 m 2 was defined as CKD 4. CKD 5 was defined as eGFR less than 15 mL/min/1.73 m 2 with no history of kidney transplantation or dialysis.…”

“… 41 Hypertension was defined as median systolic blood pressure greater than or equal to 130 mm Hg or median diastolic blood pressure greater than or equal to 80 mm Hg in 1 year. 42 Diabetes was defined as any use of antihyperglycemic medications 38 , 39 or incidence of HbA 1c greater or equal to 6.5% (to convert to proportion of total hemoglobin, multiply by 0.01). 43 Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was calculated from height and weight measurements and further categorized as underweight or weight within reference range (BMI <25), overweight (BMI >25 to <30), or obese (BMI ≥30).…”

Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with covid-19 and seasonal influenza: cohort study

“…We collected demographic information from the CDW patient domain and VA vital status database, as well as disease history from both the CDW inpatient encounter and outpatient encounter domains. [8][9][10] Exposures Exposures in the study were admission to hospital with seasonal influenza and admission to hospital with covid-19, defined on the basis of a positive laboratory test result for seasonal influenza or covid-19 with a hospital admission within five days before the test or within 30 days after the test.…”

“…We collected demographic information from the CDW patient domain and VA vital status database, as well as disease history from both the CDW inpatient encounter and outpatient encounter domains. 8 9 10 …”

“…We used the CDW pharmacy domain and CDW bar code medication administration domain to collect medication data and the CDW vital signs domain to collect vital measurements. We collected demographic information from the CDW patient domain and VA vital status database, as well as disease history from both the CDW inpatient encounter and outpatient encounter domains 8910…”