Browsing by Subject "Sodium-Glucose Transporter 2 Inhibitors"

Filter results by typing the first few letters
Now showing 1 - 6 of 6
  • Thumbnail Image
    ItemOpen Access
    Acute Coronary Syndrome: Diagnosis and Initial Management.
    (American family physician, 2024-01) Nohria, Raman; Viera, Anthony J
    Acute coronary syndrome (ACS) is defined as reduced blood flow to the coronary myocardium manifesting as ST-segment elevation myocardial infarction or non-ST-segment elevation ACS, which includes unstable angina and non-ST-segment elevation myocardial infarction. Common risk factors include being at least 65 years of age or a current smoker or having hypertension, diabetes mellitus, hyperlipidemia, a body mass index greater than 25 kg per m2, or a family history of premature coronary artery disease. Symptoms most predictive of ACS include chest discomfort that is substernal or spreading to the arms or jaw. However, chest pain that can be reproduced with palpation or varies with breathing or position is less likely to signify ACS. Having a prior abnormal cardiac stress test result indicates increased risk. Electrocardiography changes that predict ACS include ST depression, ST elevation, T-wave inversion, or presence of Q waves. No validated clinical decision tool is available to rule out ACS in the outpatient setting. Elevated troponin levels without ST-segment elevation on electrocardiography suggest non-ST-segment elevation ACS. Patients with ACS should receive coronary angiography with percutaneous or surgical revascularization. Other important management considerations include initiation of dual antiplatelet therapy and parenteral anticoagulation, statin therapy, beta-blocker therapy, and sodium-glucose cotransporter-2 inhibitor therapy. Additional interventions shown to reduce mortality in patients who have had a recent myocardial infarction include smoking cessation, annual influenza vaccination, and cardiac rehabilitation.
  • Thumbnail Image
    ItemOpen Access
    Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes.
    (JAMA network open, 2024-06) Edmonston, Daniel; Lydon, Elizabeth; Mulder, Hillary; Chiswell, Karen; Lampron, Zachary; Marsolo, Keith; Goss, Ashley; Ayoub, Isabelle; Shah, Raj C; Chang, Alexander R; Ford, Daniel E; Jones, W Schuyler; Fonesca, Vivian; Machineni, Sriram; Fort, Daniel; Butler, Javed; Hunt, Kelly J; Pitlosh, Max; Rao, Ajaykumar; Ahmad, Faraz S; Gordon, Howard S; Hung, Adriana M; Hwang, Wenke; Bosworth, Hayden B; Pagidipati, Neha J

    Importance

    Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.

    Objective

    To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.

    Design, setting, and participants

    This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023.

    Exposures

    Demographics, lifestyle factors, comorbidities, medications, and laboratory results.

    Main outcomes and measures

    Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit.

    Results

    Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment.

    Conclusions and relevance

    In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.
  • Thumbnail Image
    ItemOpen Access
    Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.
    (Stroke, 2021-05) Zhou, Zien; Jardine, Meg J; Li, Qiang; Neuen, Brendon L; Cannon, Christopher P; de Zeeuw, Dick; Edwards, Robert; Levin, Adeera; Mahaffey, Kenneth W; Perkovic, Vlado; Neal, Bruce; Lindley, Richard I; CREDENCE Trial Investigators*

    Background and purpose

    Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.

    Methods

    CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.

    Results

    In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).

    Conclusions

    Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
  • Thumbnail Image
    ItemOpen Access
    Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes.
    (The American journal of cardiology, 2024-06) Edmonston, Daniel; Mulder, Hillary; Lydon, Elizabeth; Chiswell, Karen; Lampron, Zachary; Shay, Christina; Marsolo, Keith; Jones, William Schuyler; Butler, Javed; Shah, Raj C; Chamberlain, Alanna M; Ford, Daniel E; Gordon, Howard S; Hwang, Wenke; Chang, Alexander; Rao, Ajaykumar; Bosworth, Hayden B; Pagidipati, Neha
    Placebo-controlled trials of sodium-glucose co-transporter-2 inhibitors demonstrate kidney and cardiovascular benefits for patients with type 2 diabetes and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare the outcomes for empagliflozin and DPP4i initiators with type 2 diabetes between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate decrease, incident end-stage kidney disease, or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Of 62,197 new users, 20,279 initiated empagliflozin and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.65 to 0.87) than DPP4is. The risks for mortality (HR 0.76, 95% CI 0.62 to 0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70 to 0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 to 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53 to 0.88) and those without CKD (HR 0.79, 95% CI 0.67 to 0.94). In conclusion, the initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes than DPP4is over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for patients without known CKD at baseline.
  • Thumbnail Image
    ItemOpen Access
    Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes.
    (Journal of the American College of Cardiology, 2024-08) Edmonston, Daniel; Mulder, Hillary; Lydon, Elizabeth; Chiswell, Karen; Lampron, Zachary; Shay, Christina; Marsolo, Keith; Shah, Raj C; Jones, W Schuyler; Gordon, Howard; Hwang, Wenke; Ayoub, Isabella; Ford, Daniel; Chamberlain, Alanna; Rao, Ajaykumar; Fonseca, Vivian; Chang, Alexander; Ahmad, Faraz; Hung, Adriana; Hunt, Kelly; Butler, Javed; Bosworth, Hayden B; Pagidipati, Neha

    Background

    Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed.

    Objectives

    The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D.

    Methods

    Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes.

    Results

    The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status.

    Conclusions

    SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317).
  • Thumbnail Image
    ItemOpen Access
    Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors Among Medicare Beneficiaries Hospitalized for Heart Failure.
    (Journal of cardiac failure, 2022-04) Vaduganathan, Muthiah; Greene, Stephen J; Zhang, Shuaiqi; Solomon, Nicole; Chiswell, Karen; Devore, Adam D; Butler, Javed; Heidenreich, Paul A; Huang, Joanna C; Kittleson, Michelle M; Joynt Maddox, Karen E; Mcdermott, James J; Owens, Anjali Tiku; Peterson, Pamela N; Solomon, Scott D; Vardeny, Orly; Yancy, Clyde W; Fonarow, Gregg C

    Background

    The sodium-glucose cotransporter-2 (SGLT-2) inhibitors form the latest pillar in the management of heart failure with reduced ejection fraction (HFrEF) and appear to be effective across a range of patient profiles. There is increasing interest in initiating SGLT-2 inhibitors during hospitalization, yet little is known about the putative benefits of this implementation strategy.

    Methods

    We evaluated Medicare beneficiaries with HFrEF (≤ 40%) hospitalized at 228 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry in 2016 who had linked claims data for ≥ 1 year postdischarge. We identified those eligible for dapagliflozin under the latest U.S. Food and Drug Administration label (excluding estimated glomerular filtration rates < 25 mL/min per 1.73 m2, dialysis and type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age ≥ 75 years, gender, race, hospital region, kidney function, diabetes status, triple therapy). We then projected the potential benefits of implementation of dapagliflozin based on the risk reductions observed in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial.

    Results

    Among 7523 patients hospitalized for HFrEF, 6576 (87%) would be candidates for dapagliflozin (mean age 79 ± 8 years, 39% women, 11% Black). Among eligible candidates, discharge use of β-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+β-blocker+MRA) was recorded in 88%, 64%, 29%, 3%, and 20%, respectively. Among treatment-eligible patients, the 1-year incidence (95% CI) of mortality was 37% (36-38%) and of HF readmission was 33% (32-34%), and each exceeded 25% across all key subgroups. Among 1333 beneficiaries eligible for dapagliflozin who were already on triple therapy, the 1-year incidence of mortality was 26% (24%-29%) and the 1-year readmission due to HF was 30% (27%-32%). Applying the relative risk reductions observed in DAPA-HF, absolute risk reductions with complete implementation of dapagliflozin among treatment-eligible Medicare beneficiaries are projected to be 5% (1%-9%) for mortality and 9% (5%-12%) for HF readmission by 1 year. The projected number of Medicare beneficiaries who would need to be treated for 1 year to prevent 1 death is 19 (11-114), and 12 (8-21) would need to be treated to prevent 1 readmission due to HF.

    Conclusions

    Medicare beneficiaries with HFrEF who are eligible for dapagliflozin after hospitalization due to HF, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. If the benefits of reductions in death and hospitalizations due to HF observed in clinical trials can be fully realized, the absolute benefits of implementation of SGLT-2 inhibitors among treatment-eligible candidates are anticipated to be substantial in this high-risk postdischarge setting.