SGLT2 Research Articles

Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to exhibit antiarrhythmic effects. However, there is conflicting evidence regarding the association between SGLT2 inhibitors and ventricular arrhythmias or sudden cardiac death (SCD). We utilized the US FDA Adverse Event Reporting System (FAERS) database to investigate the reporting frequencies of SGLT2 inhibitors with ventricular arrhythmias and SCD compared to other glucose-lowering drugs (ATC-A10B). We used the web data mining tool AERSMine to mine reports of ventricular arrhythmias and SCD from FAERS to compare SGLT2 inhibitors versus other glucose-lowering drugs. The mining range was from 2004q1 to 2023q3. Disproportionality analysis used the proportional reporting ratio (PRR) with 95% confidence interval (CI) and information component (IC) with 95% credible interval. From 2004q1 to 2023q3, a total of 121,129 adverse events were reported for SGLT2 inhibitors, with a total of 1,127,485 in the ATC-A10B group. Ventricular arrhythmias reporting frequency in the SGLT2 inhibitors group was similar to that of the control group (1.36/1000 reports vs 1.55/1000 reports; p = 0.10), with a PRR of 0.88 (95%CI 0.75-1.03). However, the reporting frequency of SCD in the SGLT2 inhibitors group was significantly lower than that of the control group (1.43 vs 4.70/1000; p < 0.001), with a PRR of 0.30 (95%CI 0.26-0.35), and this trend was observed within individual molecules of SGLT2 inhibitors. During the sensitivity analysis process, the results obtained when restricting the scope of data mining to between 2013q1 and 2023q3 were similar to those obtained when using data from 2004q1 to 2023q3. In this drug pharmacovigilance assessment, the reporting frequency of ventricular arrhythmias associated with SGLT2 inhibitors was similar to that of other antidiabetic medications, while the reporting frequency of SCD related to SGLT2 inhibitors was lower. This real-world study evidence complements existing clinical evidence.

Cardiovascular Disease in Patients with Chronic Kidney Disease: Current Understanding, Preventative Strategies, and Future Directions.

Chronic kidney disease (CKD) presents a significant burden on global health, with cardiovascular disease (CVD) being a leading cause of mortality in this population. Despite advancements in pharmacotherapies, preventing CVD in CKD patients remains challenging due to the intricate interplay of traditional risk factors and novel pathophysiological processes. This review aims to elucidate the current understanding of CVD prevention in CKD, encompassing epidemiology, risk factors, diagnostic considerations, and pharmacological therapeutic strategies. CKD patients exhibit a unique cardiovascular risk profile characterized by traditional risk factors such as hypertension and dyslipidemia, as well as CKD-specific factors including albuminuria, vascular calcification, and valvulopathies. The utility of coronary artery calcium scoring in risk stratification and the efficacy of aspirin, lipid-lowering agents, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists in CVD prevention are discussed. Despite promising findings, challenges such as lack of specific guidelines and data gaps persist, highlighting the need for multidisciplinary efforts to address the CVD burden in the CKD population effectively. Further research is warranted to optimize preventative strategies and improve outcomes in this high-risk population.

SGLT2 inhibitor downregulates ANGPTL4 to mitigate pathological aging of cardiomyocytes induced by type 2 diabetes

BackgroundSenescence is recognized as a principal risk factor for cardiovascular diseases, with a significant association between the senescence of cardiomyocytes and inferior cardiac function. Furthermore, type 2 diabetes exacerbates this aging process. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) has well-established cardiovascular benefits and, in recent years, has been posited to possess anti-aging properties. However, there are no reported data on their improvement of cardiomyocytes function through the alleviation of aging. Consequently, our study aims to investigate the mechanism by which SGLT2i exerts anti-aging and protective effects at the cardiac level through its action on the FOXO1-ANGPTL4 pathway.MethodsTo elucidate the underlying functions and mechanisms, we established both in vivo and in vitro disease models, utilizing mice with diabetic cardiomyopathy (DCM) induced by type 2 diabetes mellitus (T2DM) through high-fat diet combined with streptozotocin (STZ) administration, and AC16 human cardiomyocyte cell subjected to stimulation with high glucose (HG) and palmitic acid (PA). These models were employed to assess the changes in the senescence phenotype of cardiomyocytes and cardiac function following treatment with SGLT2i. Concurrently, we identified ANGPTL4, a key factor contributing to senescence in DCM, using RNA sequencing (RNA-seq) technology and bioinformatics methods. We further clarified ANGPTL4 role in promoting pathological aging of cardiomyocytes induced by hyperglycemia and hyperlipidemia through knockdown and overexpression of the factor, as well as analyzed the impact of SGLT2i intervention on ANGPTL4 expression. Additionally, we utilized chromatin immunoprecipitation followed by quantitative real-time PCR (ChIP-qPCR) to confirm that FOXO1 is essential for the transcriptional activation of ANGPTL4.ResultsThe therapeutic intervention with SGLT2i alleviated the senescence phenotype in cardiomyocytes of the DCM mouse model constructed by high-fat feeding combined with STZ, as well as in the AC16 model stimulated by HG and PA, while also improving cardiac function in DCM mice. We observed that the knockdown of ANGPTL4, a key senescence-promoting factor in DCM identified through RNA-seq technology and bioinformatics, mitigated the senescence of cardiomyocytes, whereas overexpression of ANGPTL4 exacerbated it. Moreover, SGLT2i improved the senescence phenotype by suppressing the overexpression of ANGPTL4. In fact, we discovered that SGLT2i exert their effects by regulating the upstream transcription factor FOXO1 of ANGPTL4. Under conditions of hyperglycemia and hyperlipidemia, compared to the control group without FOXO1, the overexpression of FOXO1 in conjunction with SGLT2i intervention significantly reduced both ANGPTL4 mRNA and protein levels. This suggests that the FOXO1-ANGPTL4 axis may be a potential target for the cardioprotective effects of SGLT2i.ConclusionsCollectively, our study demonstrates that SGLT2i ameliorate the pathological aging of cardiomyocytes induced by a high glucose and high fat metabolic milieu by regulating the interaction between FOXO1 and ANGPTL4, thereby suppressing the transcriptional synthesis of the latter, and consequently restoring cardiac function.Graphical abstract

New and future heart failure drugs.

In the past decade, our understanding of heart failure pathophysiology has advanced significantly, resulting in the development of new medications such as angiotensin-neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors and oral soluble guanylate cyclase stimulators. Backed by positive findings from large randomized controlled trials, recommendations for their use were recently included in the 2022 AHA/ACC/HFSA guidelines and 2023 ESC guidelines for management of heart failure. Promising drugs for future heart failure treatment include agents that modulate the neurohormonal system, vasodilators, anti-inflammatory drugs, mitotropes, which improve deranged energy metabolism of the failing heart, and myotropes, which increase cardiac contractility by affecting cardiac sarcomere function. Here, we discuss these new and future heart failure drugs. We explain their mechanisms of action, critically evaluate their performance in clinical trials and summarize the clinical scenarios in which the latest guidelines recommend their use. This Review aims to offer clinicians and researchers a comprehensive overview of novel therapeutic classes in heart failure treatment.

Effects of dapagliflozin on liver steatosis in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD) is a common liver comorbidity with considerable global consequences. This study explores the efficacy of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor primarily used to manage type 2 diabetes, in reducing liver steatosis among NAFLD patients. This randomized, open-label, two-arm, parallel-group trial enrolled patients with NAFLD and a controlled attenuation parameter (CAP) score of ≥ 252dB/m. Participants were randomized (1:1) into either the control or dapagliflozin groups. The primary outcome was the change in CAP scores, measured with FibroScan after 24weeks. The trial included 150 patients, 20 of whom (13%) had type 2 diabetes. In week 24, the dapagliflozin group had significantly lower CAP score and fatty liver grade than did the control group (266.3 ± 57.8 50 vs 298.6 ± 59.0dB/m, respectively [p = 0.002]; 1.7 ± 0.7 vs 2.2 ± 0.8, respectively [p < 0.001]). Liver stiffness, waist circumference, and alanine transaminase levels decreased in both the dapagliflozin and control groups, but the between-group differences were nonsignificant (1.0 ± 0.3 vs 1.1 ± 0.3 [p = 0.678], 94.2 ± 12.7 vs 92.4 ± 11.1 [p = 0.382], and 28.8 ± 18.3 vs 28.3 ± 14.2 U/L [p = 0.856], respectively). In the multivariate analysis, a reduction in CAP was associated with dapagliflozin treatment (p = 0.01) and changes in BMI (p = 0.007). No adverse events were observed. Dapagliflozin can reduce CAP score and fatty liver grade in patients with moderate to severe NAFLD, regardless of their diabetes status.

Correction: Sodium-Glucose Cotransporter-2 Inhibitors versus Glucagon-Like Peptide 1 Receptor Agonists Effects on Kidney and Clinical Outcomes in Veterans with Type 2 Diabetes.

Correction: Sodium-Glucose Cotransporter-2 Inhibitors versus Glucagon-Like Peptide 1 Receptor Agonists Effects on Kidney and Clinical Outcomes in Veterans with Type 2 Diabetes.

Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview ofits Chemistry, Pharmacology, and Toxicology.

Empagliflozin is a sodium glucose co-transporter-2 (SGLT2) inhibitor that has gained significant attention in the treatment of type 2 diabetes mellitus. Understanding its chemistry, pharmacology, and toxicology is crucial for the safe and effective use of this medication. This review aims to provide a comprehensive overview of the chemistry, pharmacology, and toxicology of empagliflozin, synthesizing the available literature to present a concise summary of its properties and implications for clinical practice. A systematic search of relevant databases was conducted to identify studies and articles related to the chemistry, pharmacology, and toxicology of empagliflozin. Data from preclinical and clinical studies, as well as post-marketing surveillance reports, were reviewed to provide a comprehensive understanding of the topic. Empagliflozin is a selective SGLT2 inhibitor that works by constraining glucose reabsorption in the kidneys, causing increased urinary glucose elimination. Its unique mechanism of action provides glycemic control, weight reduction, and blood pressure reduction. The drug's chemistry is characterized by its chemical structure, solubility, and stability. Pharmacologically, empagliflozin exhibits favorable pharmacokinetic properties with rapid absorption, extensive protein binding, and renal elimination. Clinical studies have demonstrated its efficacy in improving glycemic control, reducing cardiovascular risks, and preserving renal function. However, adverse effects, for instance, urinary tract infections, genital infections, and diabetic ketoacidosis have been reported. Toxicological studies indicate low potential for organ toxicity, mutagenicity, or carcinogenicity. Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium of antidiabetic medications, offering significant benefits to patients suffering from type 2 diabetes mellitus. This study covers all aspects of empagliflozin, including its history, chemistry, pharmacology, and various clinical studies, case reports, and case series.

Sodium-glucose cotransporter 2 inhibitors in acute heart failure: the EMPULSE trial and literature review

In heart failure management, hospitalization is the main cause of medical costs and is associated with an increased risk of adverse events. This review reports evidence on hospitalization as the ideal setting for disease-modifying therapy implementation, with a particular focus on gliflozins in patients with stabilized acute heart failure. The authors analyze data from the EMPULSE trial, the largest clinical study that evaluated a gliflozin in acute heart failure in patients with both reduced and preserved systolic function. The win ratio approach for statistical analysis is also discussed. The EMPULSE trial showed that empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. Subsequent analyses have also highlighted favorable effects in terms of decongestion. Since clinical benefits due to gliflozin use occur early (after a few weeks) and in order to increase heart failure polypharmacy tolerability, the initiation of gliflozin treatment should be a priority over other treatment titration. Even in complex clinical settings, as in the elderly and in patients with kidney disease, evidence supports safety and good tolerability of gliflozins, which may facilitate initiation/titration of other treatments.

SGLT2 inhibitors and NLRP3 inflammasome: potential target in diabetic kidney disease.

Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) worldwide. The pathogenesis of DKD is influenced by functional, histopathological, and immune mechanisms, including NLRP3 inflammasome activity and oxidative stress. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown metabolic benefits and the ability to slow the progression of DKD in several clinical studies over the years. Recent studies suggest that the antidiabetic activity also extends to inhibition of the inflammatory response, including modulation of the NLRP3 inflammasome, reduction of pro-inflammatory markers and reduction of oxidative stress. Here we review the efficacy of SGLT2i in the treatment of CKD and discuss the role of the inflammatory response in the development of DKD, including its relationship to the NLRP3 inflammasome and oxidative stress.

Incidence of ketoacidosis in diabetic patients treated with sodium–glucose cotransporter-2 inhibitors: A prospective cohort study

Introduction: Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have gained significant attention for their benefits in managing type 2 diabetes mellitus (T2DM), particularly in patients with chronic kidney disease (CKD) and heart failure. However, the potential for SGLT2is to increase the risk of ketoacidosis, particularly euglycemic diabetic ketoacidosis (EDKA), warrants further investigation. This prospective cohort study assesses the incidence of ketoacidosis among T2DM patients treated with SGLT2is and examines related risk factors. Methods: This is a prospective study included 575 patients with T2DM. Patients over 18 years undergoing SGLT2i therapy were followed for six months. Baseline demographics, clinical history, glucose management practices, and medication use, with an emphasis on SGLT2is, were recorded. Blood gas analysis (BGA) and urine ketones were measured monthly. Ketoacidosis was defined by urine ketone positivity with pH &lt;7.30, bicarbonate (HCO3) ≤18 mEq/L, and an elevated anion gap. Results: Out of 575 patients, 35.6% (205) had positive urine ketones at least once during the study, with 11 patients (0.7%) meeting ketoacidosis criteria. Patients with ketoacidosis had a mean hospital stay of 8.2 days compared to 5.4 days in non-ketoacidosis patients (p = 0.02). No in-hospital mortality occurred among ketoacidosis patients. Conclusion: Ketoacidosis was rare but clinically relevant in T2DM patients on SGLT2is. The incidence of euglycemic ketoacidosis highlights the need for monitoring and identifying high-risk individuals early during SGLT2i treatment initiation.

SGLT2 Inhibitors in Cardiovascular Medicine: Panacea or Pandora's Box?

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are antidiabetic agents that effectively lower blood glucose levels in patients with Type 2 Diabetes Mellitus (T2DM). Beyond their glycemic control properties, SGLT2 inhibitors have demonstrated significant cardiovascular benefits, including reductions in major adverse cardiovascular events. However, the limitations of the pivotal trials investigating these outcomes have not been fully explored. This letter aims to critically assess the major randomized clinical trials that evaluated the cardiovascular effects of SGLT2 inhibitors, highlighting both their strengths and limitations.

Correlation between the utilization of sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of dementia: a nationwide population-based study in Taiwan.

The impact of sodium-glucose cotransporter 2 inhibitors (SLGT2i) usage on reducing the risk of dementia remains uncertain. Our research seeks to establish the association between dementia risk and SLGT2 inhibitors among individuals with diabetes.This study relied on data from the Taiwan National Health Insurance Database (NHIRD), which was established in 1995 coinciding with the launch of the National Health Insurance (NHI) program by the Taiwanese government. The NHI program was implemented to enhance the healthcare system and public health in Taiwan. Patients with type 2 diabetes mellitus (T2DM) administered SGLT2i between 2016 and 2019 were included in the SGLT2i cohort. The comparison cohort consisted of patients who did not receive SGLT2i, propensity score matching by sex, age (in 5-y intervals), index date year, insurance fee, urbanization, comorbidities, and medications, with a 1:1 ratio of the exposure group.SGLT2i users had a significantly lower risk of dementia than non-SGLT2i users after adjusting for age, sex, insurance fees, urbanization, comorbidities, and medications (adjusted HR = 0.53, 95%CI: 0.50-0.57).The results revealed that patients treated with SGLT2i have a lower risk of dementia in Taiwan.

Cardiovascular Disease & Diabetes Statistics in Korea: Nationwide Data 2010 to 2019.

This study aimed to provide updated insights into the incidence and management of cardiovascular disease (CVD) in Korean adults with diabetes. Using data from the Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey, we analyzed the representative national estimates of CVD in adults with diabetes. The age- and sex-standardized incidence rate of ischemic heart disease (IHD), ischemic stroke, and peripheral artery disease (PAD) decreased from 2010 to 2019 in individuals with type 2 diabetes mellitus (T2DM). However, an increase in the incidence of heart failure (HF) was observed during the same period. Only 4.96% of adults with diabetes and CVD achieved optimal control of all three risk factors (glycemic levels, blood pressure, and lipid control). Additionally, high-intensity statin treatment rates were 8.84% and 9.15% in individuals with IHD and ischemic stroke, respectively. Treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a glucagon-like peptide-1 receptor agonist (GLP-1RA) was relatively low in 2019, with only 11.87%, 7.10%, and 11.05% of individuals with IHD, ischemic stroke, and HF, respectively, receiving SGLT2i treatment. Furthermore, only 1.08%, 0.79%, and 1.06% of patients with IHD, ischemic stroke, and HF, respectively, were treated with GLP-1RA. The incidence of most CVD (IHD, ischemic stroke, and PAD) decreased between 2010 and 2019, whereas the incidence of HF increased. The overall use of high-intensity statins, SGLT2i, and GLP-1RA remained low among individuals with T2DM and CVD.

Real-Life Individual Comparison of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Heart Failure and Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are breakthrough agents for the treatment of type 2 diabetes mellitus (T2DM) and heart failure (HF). However, among patients with HF and T2DM, some uncertainty remains about individual comparisons, including dosing. We aimed to make a real-life individual comparison of SGLT2is among patients with HF and T2DM. This was a subgroup analysis of the Turkish Ministry of Health's National Electronic Database for adult patients with HF (TRends-HF). All-cause mortality (ACM) data up to 7 years were evaluated. Patients with HF and T2DM who were prescribed an SGLT2i were identified, and individual doses of empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg were compared. For individual comparisons, propensity score-matching analysis was generated as 1:1:1, and disease-modifying therapies (DMTs) for HF were considered. In the triple-matched cohort, 1-, 5-, and 7-year survival rates were 95%, 81%, and 76% versus 94%, 78%, and 72% versus 94%, 80%, and 75% for empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg, respectively. Among patients who were on triple DMT for HF, 1-, 5-, and 7-year survival rates were 95%, 78%, and 70% for empagliflozin 25 mg, 95%, 74%, and 66% for empagliflozin 10 mg, and 94%, 77%, and 69% for dapagliflozin, respectively. Annual emergency department visits were slightly lower with empagliflozin 10 mg and dapagliflozin 10 mg than with empagliflozin 25 mg. A greater proportion of patients on dapagliflozin 10 mg did not experience hospitalization during the 7-year follow-up compared with both doses of empagliflozin, albeit with a small effect size. Among patients with HF and T2DM, SGLT2is are instrumental, and empagliflozin 10 mg remains significantly inferior to dapagliflozin 10 mg and empagliflozin 25 mg in terms of 5- and 7-year ACM.

Kidney hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in diabetes: physiology and clinical implications

Abstract The progressive loss of kidney function in diabetes mellitus is partly attributable to the occurrence of glomerular hyperfiltration. Consequently, therapeutic interventions that lower intra-glomerular pressure are a cornerstone of treatment in diabetic kidney disease. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce glomerular filtration rate (GFR) and calculated intraglomerular pressures across studies. However, the net effect on arteriolar tone that leads to acute GFR declines may differ between cohorts. While pre-glomerular vasoconstriction appears to be the dominant mechanism responsible for GFR dipping in patients with type 1 diabetes (T1D) and glomerular hyperfiltration, other factors, including postglomerular vasodilation, may contribute to the acute GFR decline in normofilterering individuals with T1D and type 2 diabetes. Regardless of the responsible mechanisms, acute changes in GFR are associated with long-term kidney function preservation—a relationship that may reflect an underlying protective decline in glomerular hypertension.

A Systematic Review and Meta-analysis on the Safety and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor Use in Hospitalized Patients.

The safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in hospitalized patients are unclear. To evaluate outcomes of inpatient SGLT2 inhibitor use. MEDLINE, Embase, Emcare, and Cochrane databases were searched through 29 May 2024. Randomized controlled trials (RCTs) and observational cohort studies with assessment of SGLT2 inhibitor use in patients hospitalized for any reason were included. Study characteristics and clinical outcomes were extracted. We performed a random-effects meta-analysis analyzing RCTs and cohort studies separately. Heterogeneity was quantified with the I2 statistic. Twenty-three RCTs comprising 19,846 participants (29.5% with type 2 diabetes) with comparison of SGLT2 inhibitors with placebo or active comparator were included. Ketoacidosis rates were 0.210 per 100 person-years (95% CI 0.119, 0.370) for SGLT2 inhibitors and 0.140 per 100 person-years (95% CI 0.070, 0.280) for control (rate ratio 1.50 [95 CI 0.56, 4.23], P = 0.38). SGLT2 inhibitor use was associated with fewer readmissions and urgent visits (odds ratio [OR] 0.64 [95 CI 0.47, 0.86], P < 0.01) and lower mortality rates (OR 0.74 [95% CI 0.56, 0.98], P = 0.03) in heart failure trials and lower incidence of acute kidney injury (OR 0.76 [95% CI 0.60, 0.97], P = 0.03) among all RCTs. Twenty observational studies were included and did not show increased adverse events. Ketoacidosis rates were low, likely leading to lack of power to detect significant differences. SGLT2 inhibitor use among hospitalized patients was associated with numerically higher rates of ketoacidosis, although further studies are required.

European Society of Cardiology (ESC) guidelines on atrial fibrillation 2024 : What is new and what is important?

The 2024 guidelines of the European Society of Cardiology (ESC) on atrial fibrillation (AF) present current and comprehensive recommendations for the diagnosis, prevention and treatment of AF. They are based on the AF-CARE treatment pathway, which includes modification of cardiovascular risk factors, stroke prevention, symptom management and continuous re-evaluation. Accordingly, all patients with newly diagnosed AF should undergo transthoracic echocardiography. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended for the treatment of heart failure across all clinical and echocardiographic levels of left ventricular ejection fraction (LVEF). The CHA2DS2-VASc score has been simplified to the CHA2DS2-VA score for the risk assessment of thromboembolism. For rate or rhythm control pharmacotherapy with beta-blockers, digitalis, amiodarone and flecainide are still the most important drugs. Pulmonary vein isolation is now also recommended as afirst-line treatment for paroxysmal AF. Re-evaluation of risk factors and treatment of comorbidities is also emphasized. Overall the guidelines represent a further development and update based on recent studies. They remain practical and provide clear and detailed recommendations for action that are globally recognized in the clinical practice.

Prescription Fills Among Patients With Type 2 Diabetes After Hospitalization for Acute Coronary Syndrome

Individuals with type 2 diabetes (T2D) have high rates of mortality following myocardial infarction (MI). Hospitalization is an opportunity to initiate or continue evidence-based treatment to reduce risk in individuals with T2D and acute coronary syndrome (ACS). To determine patterns of evidence-based medication use during the period of transition from admission to discharge after hospitalization for MI or coronary revascularization among individuals with T2D and ACS. This retrospective cohort study used data from the Centers for Medicare & Medicaid Services (CMS) for January 1, 2018, to June 30, 2020. Medicare beneficiaries older than 18 years with T2D with a qualifying hospitalization were included. Individuals were followed before admission (90 days prior), at discharge (≤90 days), and after discharge (91-180 days after) from a hospitalization for MI or coronary revascularization. Data analysis was performed in June 2023. Demographic data (race, sex, rural vs urban location of care, and comorbidities) were abstracted from CMS data using Master Beneficiary and Summary Files and International Statistical Classification of Diseases, Tenth Revision codes. Medicare Part D prescription fill records were examined for the following agents: (1) angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or angiotensin receptor-neprilysin inhibitors (ARNIs); (2) β-blockers; (3) platelet adenosine diphosphate receptor inhibitors (P2Y12Is); (4) statins or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is); and (5) glucagon-like peptide 1 receptor agonists (GLP-1RAs) or sodium glucose cotransporter 2 inhibitors (SGLT2Is). Logistic regression analysis was used to examine the association between covariates and lack of prescription fills in the postdischarge period. A total of 188 651 eligible Medicare beneficiaries with T2D and hospitalization for MI or coronary revascularization were identified. Their median age was 73.0 (IQR, 67.0-79.0) years, and more than half (111 982 [59.4%]) were men; 18 383 (9.7%) were Black and 153 461 (81.3%) were White. Not filling a cardiovascular medication after hospitalization was associated with not filling that medication at the time of discharge (adjusted risk ratio, 0.27 [95% CI, 0.27-0.28] for ACEIs, ARBs, or ARNIs; 0.24 [0.24-0.25] for β-blockers; 0.20 [0.19-0.20] for P2Y12Is; 0.31 [0.31-0.32] for statins or PCSK9Is; and 0.27 [0.26-0.28] for SGLT2Is or GLP-1RAs). In this cohort study of Medicare beneficiaries with T2D, longer-term medication use following hospitalization for MI was associated with medication use at the time of discharge. These findings highlight the critical importance of this period to optimize preventive care for these high-risk individuals. Further implementation science research is needed to develop strategies to improve use of these evidence-based medications.

Effect of dapagliflozin on renal haemodynamics in hyperfiltering T2D patients.

To investigate the effect of sodium-glucose co-transporter 2 inhibitor [SGLT-2i] therapy on renal haemodynamics in T2D patients with glomerular hyperfiltration. Sixty T2D patients with elevated [HYPER] and normal [NORMO] GFR were randomized to dapagliflozin 10 mg/day [DAPA/HYPER, n = 15; DAPA/NORMO, n = 15] or to metformin/glipizide [CONTROL/HYPER, n = 15; CONTROL/NORMO, n = 15] to reach similar glycaemic control after 4 months. GFR was measured with Iohexol and hyperfiltration was empirically defined as >125 mL/min/1.73 m2. GFR, renal plasma flow [RPF], mean arterial pressure [MAP], filtration fraction [FF], and renal vascular resistance [RVR] were determined before/after therapy. HbA1c decreased similarly in all 4 groups. GFR declined by ~18% in DAPA/HYPER and by ~7% in DAPA/NORMO and did not change in CONTROLS (p < 0.05 vs. DAPA). RPF remained unchanged in all four groups. Thus, FF (%) declined from 0.23 ± 0.01 to 0.18 ± 0.01 in DAPA/HYPER and from 0.17 ± 0.01 to 0.15 ± 0.01 in DAPA/NORMO and remained unchanged in CONTROLS (p < 0.05 vs. DAPA). MAP (mmHg) decreased from 95.4 ± 1.4 to 88.1 ± 1.3 in DAPA/HYPER and from 95.6 ± 1.3 to 91.8 ± 0.8 in DAPA/NORMO and remained unchanged in CONTROLS (p < 0.05 vs. DAPA). RVR [mmHg/L/min] declined in DAPA/HYPER (92.7 ± 7.8 to 80.4 ± 6.1) and DAPA/NORMO (90.1 ± 3.0 to 81.4 ± 2.1) but not in CONTROLS (p < 0.05 vs. DAPA). Despite comparable glycaemic control, dapagliflozin treatment, but not metformin and /or glipizide, reduced glomerular hyperfiltration in T2D patients and decreased both filtration fraction and renal vascular resistance. These findings suggest that a post-glomerular vasodilatory action of SGLT2 inhibitors contributes to their renal protective effect in T2D.

The potential role of Sodium/Glucose Cotransporter 2 inhibitors in the treatment of cystinuria.

The Maillard reaction is a non-enzymatic reaction between an amino acid and carbohydrate. We hypothesized that continuous washing of cystine stones with glucose could theoretically prevent growth of an existing cystine stone or even reduce its size leading to a decrease in stone events. Sodium/Glucose Cotransporter 2 (SGLT2) inhibitors, well known for inducing glucosuria, were used to test this hypothesis in an initial series of patients. Patients with cystinuria from September 2019 to May 2023 who received off-label dapaglifozin (Farxiga™) were identified. Patients were allowed to continue thiol and alkalinizing agents per standard of care. A symptomatic stone event was defined by stone passage or surgical intervention. Ten cystinuric patients were prescribed SGLT2 inhibitors with a median follow up of 13.5 months. Each patients' historic stone event rate was compared to the event rate while prescribed SGLT2 medication. Overall, 70% of patients experienced fewer stone events and half had stable stone volume during therapy. Eight patients had negative cystine capacity at baseline, yet seven experienced fewer stone events while on medication: four experienced no stone growth. One patient was taken off the SGLT2 inhibitor due to an adverse reaction; three others experienced mild, self-resolving effects and yet stayed on the medication. Cystinuric patients treated with a SGLT2 inhibitor experienced fewer stone events while on medication compared to their historic rates and exhibited decreased or stable stone growth. There were few medication related side effects. SGLT2 inhibitors may be a promising long-term therapy for patients with cystinuria.