Health Care Utilization and Costs Associated With Empagliflozin in Older Adults With Type 2 Diabetes.

OBJECTIVE: We compared health care resource utilization (HCRU) and costs for inpatient and outpatient services and dispensed medications in older adults with type 2 diabetes initiating empagliflozin versus dipeptidyl peptidase 4 inhibitors (DPP-4is). RESEARCH DESIGN AND METHODS: The study population included U.S. Medicare fee-for-service beneficiaries with diabetes (age ≥65 years) initiating empagliflozin or DPP-4is (August 2014 to September 2018). We estimated rate ratios (RRs) for HCRU outcomes using zero-inflated negative binomial regression and per-member per-year (PMPY) cost differences using generalized linear model with gamma distributions, overall and stratified by baseline cardiovascular disease (CVD), after adjusting for 143 baseline covariates using 1:1 propensity score matching. RESULTS: We identified 23,335 matched pairs (mean age 72 years, 51% with baseline CVD). HCRU rates were lower in empagliflozin versus DPP-4i initiators (number of inpatient days, RR 0.89 [95% CI 0.82, 0.97]; number of emergency department [ED] visits, 0.86 [0.82, 0.91]; number of hospitalizations, 0.86 [0.79, 0.93]; number of office visits, 0.96 [0.95, 0.98]). Inpatient cost (-$713 PMPY [95% CI -847, -579), outpatient cost (-$198 PMPY[-272, -124]), and total cost of care (-$1,109 PMPY [-1,478, -739]) were lower for empagliflozin versus DPP-4is, although diabetes medication cost was higher in empagliflozin initiators ($454 PMPY [95% CI 284, 567]). In the CVD subgroup, total cost was lower for empagliflozin initiators (-$2,005 PMPY [-2,451, -1,337]), while the difference was attenuated in the non-CVD subgroup (-$296 PMPY[-740, 148]). CONCLUSIONS: Among older adults with diabetes, empagliflozin was associated with a lower number of inpatient days, hospitalizations, ED visits, and office visits and with lower costs of care compared with DPP-4is, especially in those with history of CVD.

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study.

BACKGROUND: No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups. METHODS: We identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE - MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3-4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). RESULTS: We identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex. CONCLUSIONS: The cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study.

RATIONALE & OBJECTIVE: Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. STUDY DESIGN: Propensity score-matched cohort study. SETTING & PARTICIPANTS: 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n = 5,720). EXPOSURES: Warfarin, rivaroxaban, or apixaban. OUTCOMES: Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. ANALYTICAL APPROACH: Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. RESULTS: Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. LIMITATIONS: Few ischemic stroke events, potential residual confounding. CONCLUSIONS: In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. PLAIN-LANGUAGE SUMMARY: Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

A population-based cohort defined risk of hyperkalemia after initiating SGLT-2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors to patients with chronic kidney disease and type 2 diabetes.

Hyperkalemia is a common adverse event in patients with chronic kidney disease (CKD) and type 2 diabetes and limits the use of guideline-recommended therapies such as renin-angiotensin system inhibitors. Here, we evaluated the comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of hyperkalemia. We conducted a population-based active-comparator, new-user cohort study using claims data from Medicare and two large United States commercial insurance databases (April 2013-April 2022). People with CKD stages 3-4 and type 2 diabetes who newly initiated SGLT-2i vs. DPP-4i (141671 patients), GLP-1RA vs. DPP-4i (159545 patients) and SGLT-2i vs. GLP-1RA (93033 patients) were included. The primary outcome was hyperkalemia diagnosed in inpatient or outpatient settings. Secondary outcomes included hyperkalemia diagnosed in inpatient or emergency department setting, and serum potassium levels of 5.5 mmol/L or more. Pooled hazard ratios and rate differences were estimated after propensity score matching to adjust for over 140 potential confounders. Initiation of SGLT-2i was associated with a lower risk of hyperkalemia compared with DPP-4i (hazard ratio 0.74; 95% confidence interval 0.68-0.80) and contrasted to GLP-1RA (0.92; 0.86-0.99). Compared with DPP-4i, GLP-1RA were also associated with a lower risk of hyperkalemia (0.80; 0.75-0.86). Corresponding absolute rate differences/1000 person-years were -24.8 (95% confidence interval -31.8 to -17.7), -5.0 (-10.9 to 0.8), and -17.7 (-23.4 to -12.1), respectively. Similar findings were observed for the secondary outcomes, among subgroups, and across single agents within the SGLT-2i and GLP-1RA classes. Thus, SGLT-2i and GLP-1RA are associated with a lower risk of hyperkalemia than DPP-4i in patients with CKD and type 2 diabetes, further supporting the use of these drugs in this population.

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease.

Importance: There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). Objective: To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. Design, Setting, and Participants: This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Exposure: Statin initiation vs none. Main Outcomes and Measures: Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Results: Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. Conclusions and Relevance: In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.

What matters most to older adults: Racial and ethnic considerations in values for current healthcare planning.

BACKGROUND: Clarifying what matters most informs current care planning for adults with multiple comorbidities. We describe how adults aged 55+ rate what matters most and differences in Black and White participants. METHODS: Participants (N = 247, Age M = 63.61 ± 5.26) who self-identified as Black (n = 89), White (n = 96), or other racial and ethnic groups (n = 62) completed an online survey. Healthcare values in four domains, (1) important factors for managing health, (2) functioning, (3) enjoying life, and (4) connecting, were assessed with the What Matters Most-Structured Tool. Frailty was assessed with the FRAIL scale. RESULTS: Concerns about pain and finances were rated as the most influential when making healthcare decisions across groups. Black participants rated religious and racial, ethnic, and cultural considerations as more important in healthcare decision-making than did White participants (Black participant M = 1.93 ± 0.85 vs. White participant M = 1.26 ± 0.52), citing concerns about health equity, disparity, and representation. Across the sample, specific aspects of functioning (e.g., ability to think clearly, walk, and see) and connecting (e.g., with family and friends and with God) were highly valued. Black participants rated the ability to dress or bathe, exercise, and connect with God as more important than did White participants, and they were also more likely to rate length of life as more important relative to quality of life. Value ratings were not associated with other demographic or health factors. CONCLUSIONS: Adults aged 55+ from diverse groups highly value functioning and connections when making health decisions, with important contextual distinctions between Black participants and White participants. This study population was relatively young; future studies in older populations are needed.

Risk of Severe Hypoglycemia With Newer Second-line Glucose-lowering Medications in Older Adults With Type 2 Diabetes Stratified by Known Indicators of Hypoglycemia Risk.

BACKGROUND: Severe hypoglycemia is associated with adverse clinical outcomes. We evaluated the risk of severe hypoglycemia in older adults initiating newer glucose-lowering medications overall and across strata of known indicators of high hypoglycemia risk. METHODS: We conducted a comparative-effectiveness cohort study of older adults aged >65 years with type 2 diabetes initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA) using Medicare claims (3/2013-12/2018) and Medicare-linked-electronic health records. We identified severe hypoglycemia requiring emergency or inpatient visits using validated algorithms. After 1:1 propensity score matching, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years. Analyses were stratified by baseline insulin, sulfonylurea, cardiovascular disease (CVD), chronic kidney disease (CKD), and frailty. RESULTS: Over a median follow-up of 7 (interquartile range: 4-16) months, SGLT2i was associated with a reduced risk of hypoglycemia versus DPP-4i (HR 0.75 [0.68, 0.83]; RD -3.21 [-4.29, -2.12]), and versus GLP-1RA (HR 0.90 [0.82, 0.98]; RD -1.33 [-2.44, -0.23]). RD for SGLT2i versus DPP-4i was larger in patients using baseline insulin than in those not, although HRs were similar. In patients using baseline sulfonylurea, the risk of hypoglycemia was lower in SGLT2i versus DPP-4i (HR 0.57 [0.49, 0.65], RD -6.80 [-8.43, -5.16]), while the association was near-null in those without baseline sulfonylurea. Results stratified by baseline CVD, CKD and frailty were similar to the overall cohort findings. Findings for the GLP-1RA comparison were similar. CONCLUSIONS: SGLT2i was associated with a lower hypoglycemia risk versus incretin-based medications, with larger associations in patients using baseline insulin or sulfonylurea.

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes.

Importance: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point. Objective: To examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice. Design, Setting, and Participants: A population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021. Exposures: To control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)-matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates. Main Outcomes and Measures: The primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups. Results: New users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, -3.7; 95% CI, -5.2 to -2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, -1.8; 95% CI, -3.2 to -0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses. Conclusions and Relevance: The findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level-lowering agents in older adults with T2D.

Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics.

Importance: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk. Objective: To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). Design, Setting, and Participants: This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score-matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score-matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2. Exposures: Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2). Main Outcomes and Measures: Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching. Results: Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, -17.6 [95% CI, -24.9 to -10.4]; HHF: RD, -16.7 [95% CI, -21.7 to -11.9]), HF (modified MACE: RD, -41.1 [95% CI, -59.9 to -22.6]; HHF: RD, -50.4 [95% CI, -67.5 to -33.9]), or CKD (modified MACE: RD, -26.7 [95% CI, -41.3 to -12.3]; HHF: RD, -31.9 [95% CI, -43.5 to -20.8]). Conclusions and Relevance: In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.

Three Sides to the Story: Adherence Trajectories During the First Year of SGLT2 Inhibitor Therapy Among Medicare Beneficiaries.

OBJECTIVE: We aimed to understand the factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) adherence and longitudinal adherence trajectories in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using Medicare claims data (April 2013-December 2017), we identified 83,675 new SGLT2i users ≥66 years old with type 2 diabetes. We measured SGLT2i adherence as the proportion of days covered (PDC) during the first year of SGLT2i therapy. We used linear regression to assess the association between baseline covariates and PDC. Then we used group-based trajectory modeling to identify distinct longitudinal SGLT2i adherence groups and used a multivariable logistic regression model to examine the association between baseline covariates and membership in these adherence groups. RESULTS: Unadjusted mean PDC was 63%. Previous adherence to statins had the strongest positive association with PDC (regression coefficient 6.00% [95% CI 5.50, 6.50]), whereas female sex (-5.51% [-6.02, -5.00]), and Black race/ethnicity (-5.06% [-6.03, -4.09]) had the strongest negative association. We identified three adherence trajectory groups: low (23% of patients, mean PDC 17%), moderate (32%, mean PDC 50%), and high (45%, mean PDC 96%) adherence. More patients in the high adherence group were previously adherent to statins (odds ratio 1.43 [95% CI 1.39, 1.48]), and more women (1.28 [1.23, 1.32]) and Black patients (1.31 [1.23, 1.40]) were in the low adherence group. CONCLUSIONS: In a large population of older patients with type 2 diabetes, 45% were highly adherent during the first year of SGLT2i treatment. Female sex and Black race/ethnicity were most strongly associated with low adherence.

SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes.

RATIONALE & OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to have many benefits for patients with type 2 diabetes. However, whether SGLT2 inhibitors increase the risk of acute kidney injury (AKI) remains unknown. We examined the association of AKI hospitalization with prior initiation of an SGLT2 inhibitor compared with initiation of a dipeptidyl peptidase 4 (DPP-4) inhibitor or a glucagon-like peptide 1 receptor agonist (GLP-1RA) among older adults with type 2 diabetes in routine practice. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: Older adults aged at least 66 years with type 2 diabetes enrolled in Medicare fee-for-service and who were new users of SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1RA agents in the interval from March 2013 to December 2017. EXPOSURES: New use of an SGLT2 inhibitor versus new use of a DPP-4 inhibitor or GLP-1RA. OUTCOME: The primary outcome was hospitalization for AKI, defined as a discharge diagnosis of AKI in the primary or secondary position. ANALYTICAL APPROACH: New users of SGLT2 inhibitors were matched at a 1:1 ratio to new users of DPP-4 inhibitors or GLP-1RAs using propensity scores in 2 pairwise comparisons. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% CIs in propensity score-matched groups. RESULTS: Totals of 68,130 and 71,477 new users of SGLT2 inhibitors were matched to new users of DPP-4 inhibitors or GLP-1RAs, respectively. Overall, the mean age of study participants was 72 years. The risk of AKI was lower in the SGLT2 inhibitor group than in the DPP-4 inhibitor group (HR, 0.71 [95% CI, 0.65-0.76]) or the GLP-1RA group (HR, 0.81 [95% CI, 0.75-0.87]). LIMITATIONS: Residual confounding and lack of laboratory data. CONCLUSIONS: Among older adults with type 2 diabetes, initiation of an SGLT2 inhibitor was associated with a reduced risk of AKI compared with initiation of a DPP-4 inhibitor or a GLP-1RA.

Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

AIM: To investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitor treatment across the broad spectrum of cardiovascular risk. METHODS: In a population-based cohort study we identified 39 072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4 inhibitors, using data from 2 US commercial insurance databases and Medicare between August 2014 and September 2017. The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLAs), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for more than 140 baseline covariates. RESULTS: Study participants had a mean age of 60 years and only 28% had established cardiovascular disease. Compared to DPP-4 inhibitors, empagliflozin was associated with similar risk of MI/stroke (HR 0.99 [95% CI 0.81-1.21]), and lower risk of HHF (HR 0.48 [95% CI 0.35-0.67] and 0.63 [95% CI 0.54-0.74], based on a primary and any heart failure discharge diagnosis, respectively). The HR was 0.52 (95% CI 0.38-0.72) for all-cause mortality (ACM) and 0.83 (95% CI 0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA (HR 1.71 [95% CI 1.08-2.71]) and a decreased risk of AKI (HR 0.60 [95% CI 0.43-0.85]). CONCLUSIONS: In clinical practice, the initiation of empagliflozin versus a DPP-4 inhibitor was associated with a lower risk of HHF, ACM and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information.

Association of Medicare's Bundled Payment Reform With Changes in Use of Vitamin D Among Patients Receiving Maintenance Hemodialysis: An Interrupted Time-Series Analysis.

BACKGROUND & RATIONALE: Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D analogues are the biggest drug cost drivers in hemodialysis (HD) patients, but the association between PPS introduction and vitamin D therapy has been scarcely investigated. STUDY DESIGN: Interrupted time-series analyses. SETTING & PARTICIPANTS: Adult US HD patients represented in the US Renal Data System between 2008 and 2013. EXPOSURES: PPS implementation. OUTCOMES: The cumulative dose of IV vitamin D analogues (paricalcitol equivalents) per patient per calendar quarter in prevalent HD patients. The average starting dose of IV vitamin D analogues and quarterly rates of new vitamin D use (initiations/100 person-months) in incident HD patients within 90 days of beginning HD therapy. ANALYTICAL APPROACH: Segmented linear regression models of the immediate change and slope change over time of vitamin D use after PPS implementation. RESULTS: Among 359,600 prevalent HD patients, IV vitamin D analogues accounted for 99% of the total use, and this trend was unchanged over time. PPS resulted in an immediate 7% decline in the average dose of IV vitamin D analogues (average baseline dose = 186.5 µg per quarter; immediate change = -13.5 µg [P < 0.001]; slope change = 0.43 per quarter [P = 0.3]) and in the starting dose of IV vitamin D analogues in incident HD patients (average baseline starting dose = 5.22 µg; immediate change = -0.40 µg [P < 0.001]; slope change = -0.03 per quarter [P = 0.03]). The baseline rate of vitamin D therapy initiation among 99,970 incident HD patients was 44.9/100 person-months and decreased over time, even before PPS implementation (pre-PPS ß = -0.46/100 person-months [P < 0.001]; slope change = -0.19/100 person-months [P = 0.2]). PPS implementation was associated with an immediate change in initiation levels (by -4.5/100 person-months; P < 0.001). LIMITATIONS: Incident HD patients were restricted to those 65 years or older. CONCLUSION: PPS implementation was associated with a 7% reduction in the average dose and starting dose of IV vitamin D analogues and a 10% reduction in the rate of vitamin D therapy initiation.