Use Of Sodium-glucose Cotransporter-2 Inhibitors Research Articles

Abstract 4113885: Impact of Sodium-glucose Cotransporter 2 Inhibitor on Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure

Background: Catheter ablation for Atrial fibrillation (AF) has been proven to improve the prognosis in patients with heart failure (HF), while it remains a high risk for AF recurrence and adverse cardiovascular outcomes. The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in HF patients after AF ablation is unknown. Method: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups based on the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n=368) and non-SGLT2i using (n=368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. Results: During a total of 1315 person-year follow-ups, AF recurrence occurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted HR = 0.56, 95% CI: 0.43-0.74, P<0.001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted HR = 0.58, 95%CI: 0.41-0.80, p = 0.001). Although there was a tendency towards benefits, significant differences in all-cause mortality (adjusted HR = 0.76, 95%CI: 0.35-1.63, p = 0.480), cardiovascular mortality (adjusted HR = 0.62, 95%CI: 0.24-1.57, p = 0.312) and thrombotic events (adjusted HR = 0.40, 95%CI: 0.16-1.03, p = 0.056) were not noted between groups. Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Abstract 4138611: Impact of SGLT-2 Inhibitor Use on Atrial Fibrillation Incidence Following Heart Failure Hospitalization

Introduction: The development of atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated cardiovascular benefit in patients with both preserved and reduced ejection fractions. Meta analysis of prospective trials suggest reduced incidence and burden of atrial fibrillation in patients taking SGLT-2 inhibitors, though this has not been specifically addressed in prospective trials. Hypothesis: SGLT-2 inhibitors reduce the incidence of atrial fibrillation in patients with heart failure. Aim: The goal of the study is to assess the impact of SGLT-2 inhibitor on the incidence of atrial fibrillation following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was development of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF after HF hospitalization. Results: Among the 3,953 patients included in our study, 704 (17.8%) patients were prescribed SGLT-2 inhibitors. Of those taking SGLT-2 inhibitors, 559 (79.4%) patients had diabetes. SGLT-2 inhibitor use is associated with significant reduction of AF at one year ( p<0.001; RR 0.65; 95% CI: 0.51-.81 ). This finding was consistent across patients with reduced ejection fractions (EF<50%) ( p=0.001; RR 0.56; 95% CI: 0.40-.80 ) and preserved ejection fraction (EF>50%)( p=0.001; RR 0.58; 95% CI: 0.42-0.80 ). Conclusion: In patients with reduced ejection fraction and preserved ejection fraction heart failure, use of an SGLT-2 inhibitor is associated with a statistically significant lower risk of new-onset atrial fibrillation at one year following HF hospitalization.

Abstract 4134772: Optimizing Heart Failure with Preserved Ejection Fraction Management: Quality Review of SGTL2 Inhibitor Use

Heart failure with preserved ejection fraction (HFpEF) remains a diagnostic challenge despite a 50% incidence of HF admissions. H2FPEF tool is a validated scoring system that estimates HFpEF probability with a sensitivity of 69% and positive predictive value of 85%. Despite clinical research interest and therapeutic advances in HFpEF, implementation of therapies remain inconsistent. Currently ACC/AHA guidelines classify sodium-glucose cotransporter 2 inhibitors (SGLT2i) use a 2A recommendation with benefits for reducing hospital admissions. We assess the utilization of current guidelines. An observational retrospective analysis was performed of patients >18 years with a left ventricular ejection fraction of >50% seen in cardiology clinic with an ICD.10 code of diastolic heart failure from January 2022 to 2024 at a large tertiary hospital. Electronic records were reviewed for patient demographics, documentation of heart failure diagnosis, medication list and echocardiogram parameters. Primary outcome was HF related hospitalization. The study screened 79 patients, 51% females and 49% males. 20.2% of the patients were on SGLT2i, a quarter of which were female. Of those on SGLT2i, 56% were on diuretics, 81% had H2FpEF score > 5, 56% had diabetes, and 19% had a HF hospitalization. SGLT2i was stopped in 1 patient due to cost. Of the (63) 79.8% of patients not on SGLT2I, 65% were on diuretics, 90% had H2FPEF score > 5, 23% had diabetes and 32% had a HF hospitalization. 43% were males, with an average age of 71 for males and 62 for females. Ten patients had documented reasons for not being on SGLT2i including CKD, dialysis, yeast infection and denied insurance coverage. Unadjusted effect measures for HF hospitalization (HR 0.59, RRR 40.9%, OR 0.496; p 0.134). As guidelines are readily investigated and updated by expert consensus groups, evaluating practice patterns is key. Unlike other cardiac medications, SGLT2is are primarily initiated by cardiologists and recognizing barriers can identify generalizability of current guidelines. Our data looked at both objective and clinical endpoints for HFPEF diagnosis. Interestingly, women were less often started on SGLT2i and coverage was not a frequent cause for not using SGLT2i. Our quality metric analysis shows a potential protective effect of HF readmission with SGLT2i use in a highly symptomatic cohort, and suggests future directives need to focus on broadening educational reach among cardiologists.

Abstract 4136724: Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor Among Patients Hospitalized with Heart Failure and Preserved Ejection Fraction in the United States

Introduction: In August 2021, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) found that empagliflozin reduced rates of cardiovascular death and hospitalization by 21% in patients with heart failure with mildly reduced ejection fraction of 41-49% (HFmrEF) and with preserved ejection fraction of > 50% (HFpEF). National trends in Sodium-Glucose Cotransporter-2 Inhibitors ( SGLT2i) use among patients with HFmrEF and HFpEF following this trial are unknown. Methods: We identified patients hospitalized for HFmrEF and HFpEF in the AHA Get With The Guidelines-Heart Failure registry between July 2021 and September 2023. We examined temporal trends in SGLT2i prescriptions at discharge after the publication of the EMPEROR-Preserved trial using the Cochran-Armitage trend test. Results: Among 158,849 hospitalizations with an EF > 40% across 557 hospitals, 27,712 (17.4%) had HFmrEF, and 131,137 (82.6%) had HFpEF. Overall, 22,126 (13.9%) patients were discharged with a prescription for SGLT2i, with higher rates among those with HFmrEF (18.5% vs. 13.0% in those with HFpEF). Patients prescribed SGLT2i were more likely to be younger, male, of Black race, have type II diabetes, have Medicaid insurance, and be discharged from large hospitals. After publication of the EMPEROR-Preserved trial during Q3 2021, rates of SGLT2i prescription at hospital discharge increased from 4.2% in Q3 2021 to 23.5% in Q3 2023, with a 29% relative increase in the rate of SGLT2i prescription for each quarter (adjusted OR, 1.29 [95% CI: 1.28, 1.29]; P<.001). Prescription rates increased from 6.1% in Q3 2021 to 31.6% in Q3 2023 among patients with HFmrEF and from 3.8% to 21.9% for patients with HFpEF (Figure). Conclusion: In the U.S., the use of SGLT2i at discharge has increased for patients hospitalized with HFmrEF and HFpEF following the publication of the EMPEROR-Preserved trial. However, the majority of eligible patients hospitalized for decompensated HF remain untreated with SGLT2i, indicating the need for further efforts to apply the scientific findings into clinical practice.

Sodium-glucose cotransporter 2 inhibition in patients with liver cirrhosis and diabetes: a possible role in ascites control?

The aim of this brief report is to evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2-I) effects on patients with both refractory ascites and type 2 diabetes mellitus (T2D). We consecutively recruited all the diabetic patients with refractory ascites due to decompensated liver cirrhosis admitted between February and May 2023 at the Internal Medicine Unit of the University Hospital of Palermo. Clinical and laboratory data were collected after starting SGLT2-I therapy. SGLT2-I use was associated with a reduction/resolution of ascites and with an improvement in serum albumin and sodium levels and estimated glomerular filtration rate. SGLT2-I might represent a valid therapeutic option in the treatment of patients with refractory ascites and T2D, as already hypothesized by other research groups.

Abstract 4135113: Referral to a Heart Failure Clinic Substantially Increases the Use of Angiotensin Receptor Neprilysin Inhibitor (ARNi) and Sodium-glucose cotransporter-2 Inhibitor (SGLT2i) in Heart Failure Patients.

Introduction: Addressing access to life-saving therapy is crucial in influencing health outcomes. The stark reality of limited access to pharmacological therapy for heart failure with reduced ejection fraction (HFrEF), particularly novel drugs such as angiotensin receptor neprilysin inhibitors (ARNi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for patients with heart failure (HF), underscores the challenges we face. Hypothesis: We analyze the impact of referring patients diagnosed with HF to our HF clinic by evaluating access to the 4 pillars of HFrEF, emphasizing cost-prohibiting pharmacological therapy, and assessing the efficacy of these medications when applied. Methods: This study compared 314 patients who live in counties within and outside the Penn State Health System. The data collected included healthcare insurance coverage, HF etiology, comorbidities, onset, initial and within six months post titration of guideline-directed medical therapy (GDMT) echocardiogram, and medication dose. Results: Among patients referred to our HF clinic, 184 live in counties within, and 130 live outside the Penn State Health System. The average age was 64, 69.4% were male, and a significant number of patients had HFrEF (92.7%). The prevailing comorbidities between the 2 groups were hypertension, hyperlipidemia, and diabetes. Upon completion, there was a significant increase in ARNi (83.1%) and SGLT2i (65.3%) use in both groups. They both (within vs. outside) reached almost similar percentages of triple therapy (77.9% vs. 79.2%; p-value=0.78), except for quadruple therapy (36.4% vs. 44.6%; p-value=0.16) and maximum tolerated dose (83.3% vs. 75%; p-value=0.11). The overall mean ejection fraction (EF) in both groups demonstrated significant improvement from pre-EF (30.5%) to post-EF (45.9%). Conclusion: Despite their location, patients referred to the HF clinic experienced intensified use of cost-prohibiting medications such as ARNi and SGLT2i, compared to the current gap in GDMT use. After optimizing GDMT, both groups had markedly improved EF. These findings suggest that referral to a HF clinic is a promising strategy for addressing the use of life-saving therapy and potentially reducing adverse health outcomes.

The Incidence of Contrast-Induced Nephropathy in Patients on Sodium-Glucose Cotransporter-2 Inhibitors Following Percutaneous Coronary Intervention: An Observational Analysis.

The purpose of this study is to compare the incidence of contrast-induced nephropathy (CIN) following percutaneous coronary intervention (PCI) in patients on sodium-glucose cotransporter-2 (SGLT-2) inhibitors prior to the procedure with a matched cohort of patients not receiving sodium-glucose cotransporter-2 inhibitor therapy. In this retrospective observational study, patients were eligible for inclusion if they underwent PCI at any of the included study centers within the study time period. Patients were assigned to either the SGLT-2 inhibitor group or control group depending on the documentation of receiving any SGLT-2 inhibitors within 24h prior to PCI. Propensity matching was utilized to determine the final subjects to include for comparison. The primary outcome was the incidence of CIN. A total of 192 patients (96 in each group) were matched after exclusion criteria were applied. The incidence of contrast-induced nephropathy was similar between groups, occurring in 8 (8.3%) patients in the SGLT-2 inhibitor group and 6 (6.3%) patients in the comparator group (p = 0.58). There was also no difference between groups in the change in serum creatinine following PCI. Based on our analysis, we did not identify any risk of CIN associated with SGLT-2 inhibitor use prior to PCI. Based on these results and in conjunction with previously published literature, the use of SGLT-2 inhibitors appears safe prior to PCI. These results still warrant further investigation with prospective adequately powered studies to evaluate the incidence of CIN with SGLT-2 inhibitor use in the setting of PCI.

Nephroprotective effect of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus and hypertension: a real-world population-based cohort study

ABSTRACT Objectives This study aimed to investigate the nephroprotective effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in elderly patients with type 2 diabetes mellitus (T2DM) and hypertension based on real-world clinical data. The study aimed to provide a theoretical basis for evidence-based pharmacological treatment of chronic kidney disease in this population. Methods The ‘Health Cloud’ platform of the Shanghai Municipal Health Commission was employed to identify and screen elderly patients with T2DM and hypertension. The propensity score matching cohort was further constructed to estimate the effect of SGLT2i on the risk of rapid decline in renal function (∆eGFR≤-5 ml/min/1.73 m2 or ∆eGFR%≤-5%). Multiple sensitivity analyses were conducted to assess the robustness of the results. Results After propensity score matching, no significant differences of covariates were identified between the SGLT2i and non-SGLT2i groups. The results of multivariate logistic models demonstrated a consistent and inverse correlation between SGLT2i use and the risk of rapid eGFR decline, whether defined as ∆eGFR≤-5 ml/min/1.73 m2 (OR = 0.60, 95% CI:0.38-0.96) or ∆eGFR%≤-5%（OR = 0.57, 95% CI:0.37-0.89). In the stratification of renin-angiotensin system inhibitor (RASi) treatment, SGLT2i was associated with a lower risk of rapid eGFR decline in the RASi group (all ORs < 1, p < 0.05), with no interaction between SGLT2i and RASi (all P for interaction > 0.05) detected. Conclusions SGLT2i significantly reduced the risk of rapid eGFR decline in elderly patients with T2DM and hypertension, but the synergistic effect with RASi remains unclear.

SGLT-2 inhibitors and mortality among patients with heart failure with reduced ejection fraction: linked database study

ObjectiveTo investigate the association between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and risk of all cause mortality among patients with heart failure with reduced ejection fraction.DesignLinked database study.SettingNational registers in Denmark,...

Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study.

Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.

Sodium-Glucose Cotransporter 2 Inhibitors, Malnutrition, Cachexia, and Survival in Patients With Heart Failure With a History of Anthracycline Treatment.

Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure or worsening preexisting heart failure as well as adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in patients with heart failure previously treated with anthracyclines. Using the TriNetX research network, we identified 1545 patients with a history of SGLT2i use and 17,681 patients without a history of SGLT2i use. We then performed 1:1 propensity score matching resulting in 1323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia {hazard ratio (HR) 0.453, 95% confidence interval (CI) [0.286-0.718]}, malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients with heart failure receiving anthracycline therapy.

The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives—A Narrative Review

The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF’s development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium–glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.

Erectile Dysfunction Risk Among Patients With Diabetes Mellitus Using Sodium-Glucose Cotransporter 2 Inhibitors.

The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.

O USO DOS INIBIDORES DO COTRANSPORTADOR DE SÓDIO-GLICOSE-2 (SGLT2) NA INSUFICIÊNCIA CARDÍACA: UMA REVISÃO BIBLIOGRÁFICA

Heart failure (HF) is not a single pathological diagnosis, but a clinical syndrome caused by a structural and/or functional abnormality of the heart, resulting in elevated intracardiac pressure or inadequate cardiac output at rest or during exercise. It is a common clinical condition found in various healthcare settings, with a vast socio-economic impact. In Brazil, HF is the leading cardiovascular cause of hospital morbidity. Thus, heart failure studies play a crucial role in the development of new drugs, enabling significant improvements in the efficacy, safety and tolerability of treatment, as well as the personalization of care for individual patients. Recent advances in pharmacotherapy have led to the evolution of new therapeutic agents with a decrease in hospitalization and mortality rates in HF. The 2023 update of the European Society of Cardiology (ESC) guidelines recommends (class IA) the administration of sodium-glucose transporter 2 inhibitors (SGLT2i) for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced EF (HFpEF). This study aims to analyze the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure. In order to arrive at these topics, articles were collected from the PUBMED and SCIELO databases, and an analysis was carried out based on the material found in order to be able to explain the information relevant to the topic.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies.

To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator. Target trial emulation studies. Canadian population database, January 2014 to June 2022. 20 146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high risk group. Initiation of an SGLT-2 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist, with a dipeptidyl peptidase-4 (DPP-4) inhibitor as alternative comparator. The primary outcome was recurrent nephrolithiasis events ascertained from diagnoses during emergency department visits, hospital admissions, or outpatient visits. Secondary outcomes included nephrolithiasis resulting in hospital admission or emergency department visits and flare-up of gout, as well as a positive control outcome (genital infection) and negative control outcomes (osteoarthritis encounter and appendicitis). Poisson and Cox proportional hazards regression models were used (primary analyses), as well as overlap weighting. After inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14 456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio was 0.67 (95% confidence interval (CI) 0.57 to 0.79) and rate difference was -51 (95% CI -63 to -40) per 1000 person years, with a number needed to treat (NNT) of 20. Among those with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). Protective associations persisted for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and when an SGLT-2 inhibitor was compared with a DPP-4 inhibitor (rate ratio 0.73 (0.68 to 0.78), rate difference -38 (-46 to -29) per 1000 person years (NNT of 26)). Protective associations also persisted among patients with nephrolithiasis and concomitant gout, with a rate ratio of 0.67 (0.57 to 0.79) and rate difference of -53 (95% CI -78 to -27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and 0.63 (0.55 to 0.72) and-62 (-81 to -42) per 1000 person years, respectively, versus a DPP-4 inhibitor (NNT of 16). Furthermore, SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio 0.72, 0.54 to 0.95, rate difference -16, -31 to -1 per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and -21, -33 to -9 per 1000 person years) compared with DPP-4 inhibitors. SGLT-2 inhibitor initiators showed higher risk of genital infection (eg, hazard ratio 2.21, 95% CI 1.68 to 2.90, and rate difference 13 per 1000 person years), but no altered risk of osteoarthritis encounter (0.87, 0.68 to 1.1, and -2 per 1000 person years) or appendicitis (1.07, 0.69 to 1.67, and 1 per 1000 person years). Results were similar when propensity score overlap weighting was applied. The benefits associated with SGLT-2 inhibitor for patients with nephrolithiasis in these target trial emulations suggest they may be a useful addition to current treatments to simultaneously manage nephrolithiasis recurrence and comorbidities, including gout.

SGLT2-'eyes' on the reno-protection prize: reduction of post-PCI contrast-associated AKI in diabetic patients using SGLT2 inhibitors

Abstract Background Chronic therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) is associated with long term reno-protective benefits. There are limited data on the benefits of these agents against the risk of contrast-associated acute kidney injury (CA-AKI). Purpose The goal of our study was to assess the comparative efficacy of SGLT2i for the prevention of CA-AKI in diabetic patients undergoing PCI. Methods The study population included all diabetic patients enrolled in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Percutaneous Coronary Intervention (BMC2PCI) registry, a clinical registry of all PCI cases at non-federal hospitals in the state of Michigan, USA. Included patients underwent PCI between January 2022 and September 2023. Patients on dialysis were excluded. Predicted AKI risk was calculated using a previously validated and published machine learning BMC2 risk model. The primary outcome of CA-AKI was defined as an elevation in serum creatinine of ≥0.5 mg/dL following PCI. Risk-adjusted AKI rates were estimated by the product of event observed/expected ratio and overall collaborative AKI rate. Propensity matching on 23 covariates was used to adjust for the non-random use of SGLT2i. Results A total of 19,078 diabetic patients were included, of whom 3,087 (16.2%) were prescribed SGLT2i prior to PCI. Patients treated with SGLT2i were younger (66.1 vs 68.3 years), more likely to be men (73.3% vs 65.3%), have heart failure (50.4% vs 42.4%), have prior PCI (58.4% vs 48.8%), and have co-prescription of insulin (43.8% vs 37.3%) (p&amp;lt;0.001 for all). After propensity matching, no significant baseline difference between cohorts remained, with an absolute standardized difference less than 10% on all covariates. The pre-procedural use of SGLT2i was associated with a lower incidence of CA-AKI in unadjusted analysis (2.7% vs 3.8%, p=0.003) and after adjusting for the baseline predicted risk of CA-AKI (2.2% vs 2.8%, adjusted OR 0.69, 95% CI 0.54-0.89, p=0.0045). In a propensity-matched analysis, the use of SGLT2i was strongly associated with a reduced adjusted risk for CA-AKI (2.2 % vs 2.8%, adjusted OR 0.72, 95% CI 0.62-0.84, p=0.026). Conclusions Among patients with diabetes presenting for PCI, pre-procedural use of SGLT2i was associated with a significant reduction in the risk of CA-AKI. These results should compel further investigation into the beneficial effects of SGLT2 inhibitors in reducing the risk of CA-AKI.

Changes in N-terminal pro b-type natriuretic peptide according to SGLT2 inhibitor utilization patterns in patients hospitalized for decompensated heart failure: a prospective cohort study

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors have found success in treating patients with chronic heart failure (HF) across the entire spectrum of left ventricular ejection fraction (EF). Their benefits may also extend to patients with acute HF decompensation, as they may aid effective decongestion. Purpose This study aims to present the various patterns in changes of N-terminal pro b-type natriuretic peptide (NT-proBNP) according to SGLT2 inhibitor use in patients hospitalized for acute HF decompensation. Methods In this prospective cohort study, we enrolled consecutive patients hospitalized for HF decompensation during a 4-month period in a cardiology department. Prior medical history and cardiovascular risk factors were recorded. The patterns in SGLT2 inhibitor use were noted and patients were classified into three groups; Group 1 (No SGLT2 inhibitor use/Discontinuation), Group 2 (Prior SGLT2 inhibitor use and continuation), and Group 2 (SGLT2i-naïve and initiation). Categorization according to left ventricular (EF) to HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) was also performed. Moreover, estimated glomerular filtration rate (eGFR) was used as an estimate of renal function. Results In this analysis, 159 patients were included (median age: 79 years old, male sex: 64.8%, median duration of hospitalization: 6 days). In this population, 67.9% of the patients were not receiving a SGLT2 inhibitor on admission. Concerning demographic and clinical variables (Figure 1), there were no major differences in age, sex distribution, history of diabetes mellitus, dyslipidemia, and atrial fibrillation, as well as in renal function. Group 2 patients had a lower prevalence of arterial hypertension compared to Group 3 (36.6% vs. 52.6%, p&amp;lt;0.05). Moving to the changes in NTproBNP (Figure 2), we observed that patients who did not use SGLT2 inhibitors and did not initiate them during hospitalization had negligible changes in NTproBNP, either as an absolute change (Group 1: 506 (8792) pg/ml vs. Group 2: -5610 (9461) pg/ml vs. Group 3: -3602 (4409) pg/ml, p=0.001) or as percentage change (Group 1: -2.1 (63.4) % vs. Group 2: -30.3 (39.0) % vs. Group 3: -38.3 (41.5) %, p=0.001), compared to the rest of the study population who were already taking SGLT2 inhibitors or initiated them during hospitalization. Conclusion In this study we found NTproBNP, a widely used biomarker of congestion and prognosis in HF, was significantly reduced in decompensated HF patients receiving SGLT2 inhibitors, with the greatest change being observed in those being treatment-naïve prior to admission. These findings further highlight the role of this drug class even in the acute phase of the disease.Figure 1Figure 2

Risk of Incident colorectal carcinoma in patients with type 2 diabetes on SGLT-2 inhibitor users: a population-based cohort study

Abstract Background Patients with type 2 diabetes (T2D) are at substantially higher risk for developing colorectal carcinoma (CC) than the general population. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use on the development of incident CC in patients with T2D, but the findings are inconsistent. Purpose This study aimed to examine the association between SGLT-2i use and incident CC risk in patients with T2D. Methods We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database (2015–2021). The primary outcome was the risk of incident CC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Therefore, multiple Cox regression modeling was conducted to analyze the association between SGLT-2i use and incident CC risk in patients with T2D. Results 268,495 propensity score-matched pairs of patients with T2D using SGLT-2i and non-using SGLT-2i, 1557 and 1264 incident CCs were recorded, respectively. There was a decreased risk of incident CC for SGLT-2i users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.79, 95% CI 0.74–0.84) compared with non-SGLT-2i users. The sensitivity test for the propensity score 1:2-matched analyses showed similar result (adjusted HR 0.79, 95% CI 0.74–0.85). Conclusions This population-based cohort study found that SLGT2i user was associated with a lower risk of CC by 21% compared to non-SGLT-2i users in T2D patients. More studies are needed to credibly evaluate the effects of SGLT-2i therapy on CC prevention in patients with T2D.

What does routinely-collected electronic health record data tell us about the use of heart failure medication among older people in Wales? Making progress but could do better

Abstract Background European Society of Cardiology 2021 guidelines recommend 4 pillars of treatment to reduce mortality for those with heart failure (HF) and reduced ejection fraction (HFrEF): pillar 1) angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), pillar 2) beta-blocker (BB), pillar 3) mineralocorticoid receptor antagonist (MRA), pillar 4) sodium-glucose co-transporter 2 inhibitor (SGLT2i). When there is heart failure with preserved ejection fraction (HFpEF), guidelines recommend diuretics to alleviate congestion and treatment of risk factors such as hypertension and diabetes. Prior to 2021, United Kingdom guidelines did not include SGLT2i. Purpose To examine how HF treatment is recorded in routinely-collected electronic health record (EHR) data for older people in Wales, and to explore how that has changed since 2015. Methods We conducted a retrospective, population-level, observational study using linked anonymised EHR data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period (21.5% of population in 2022). Of these, 65,010 had a code for heart failure in their primary or secondary care records. We excluded 13,990 individuals with fewer than 12 months data pre- or post-diagnosis. We looked forward, from HF diagnosis, for codes associated with specific medications. Results The final cohort comprised 51,020 individuals aged 65y and over with a diagnosis of heart failure between 2015-2022. Incidence and prevalence of heart failure increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Preceding cardiovascular diagnoses included hypertension (69.5%), atrial fibrillation (36.7%), myocardial infarction (30.5%), coronary artery disease (25.7%), and valve disease (17.7%). Diabetes (41.7%), chronic kidney disease (30.9%) and cancer (26.4%) were the most common comorbidities. The subtype of HF (HFrEF or HFpEF) was only evident in 5,850. Treatments recorded most often were loop diuretics, ACE-I, and BB (Table 1). SGLT2i codes increased in 2020/2021(Figure 1). At 10-12 months post diagnosis, the proportion with simultaneous pillar combinations was; 27.4% 1 + 2, 12.5% 1, 2 + 3, and only 2% 1, 2, 3 + 4. Conclusions In Wales, there is a need to improve the coding of HF subtype in primary care records. We suggest interpreting data with the assumption that approximately half of the cohort are likely to have HFrEF. While the cohort proportion on ACE-I or beta-blockers may be appropriate, the proportion with more than 1 simultaneous pillar of treatment recorded appears low. The use of SGLT2i in codes is increasing. These results are important in evaluating health service delivery and in establishing baseline data from which to monitor improvements.