SGLT2 Inhibitors Research Articles

Prescribing patterns of SGLT-2 inhibitors and their association with heart failure readmissions: a single-center cross-sectional study from a low- and middle-income country.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular death and heart failure (HF) hospitalizations in patients with reduced and mildly reduced or preserved ejection fraction. This study assesses the effectiveness of SGLT2 inhibitors in reducing HF readmission rates and examines prescription patterns in hospitalized patients. This single-center retrospective cross-sectional study evaluated the impact of SGLT2 inhibitors on HF readmission rates when initiated during index hospitalization or within 14 days of discharge. Patients were divided into an SGLT2 group and a non-SGLT2 group, with 6-month readmission rates compared to the groups. Of the 234 patients, 85 (36.3%) were prescribed SGLT2 inhibitors, while 149 (63.7%) were not. SGLT2 inhibitors were prescribed less frequently to patients with chronic kidney disease (CKD) and patients admitted under cardiology services were more likely to receive SGLT2 inhibitors. Among those prescribed SGLT2 inhibitors, the median ejection fraction was significantly lower compared to those not prescribed, while the median estimated glomerular filtration rate was higher. There were 107 total readmissions (45.7%), with most (55%) occurring within 30 days of the index hospitalization. Total readmissions and 30-day readmissions were significantly lower in the SGLT2 inhibitor group (31.8% vs 53.7%, p = 0.001) and (33.33% vs 62.50%, p = 0.029), respectively. Heart failure readmissions were also lower in the SGLT2 group (29.6% vs 21.3%, p = 0.37). Our study demonstrated a significant reduction in heart failure readmission rates among patients prescribed with SGLT2 inhibitors. However, we also observed a gap in the prescription of SGLT2 inhibitors.

Design considerations for future renoprotection trials in the era of multiple therapies for chronic kidney disease.

Nephrology has benefited from conducting increasingly large high-quality trials in the last 5-10 years. In addition to the long-standing known benefits of renin-angiotensin system inhibitors, we now have multiple pharmacotherapies that provide kidney and/or cardiovascular protection for certain types of patient with chronic kidney disease (CKD). These include sodium-glucose co-transporter 2 inhibitors (SGLT2i), a non-steroidal mineralocorticoid receptor antagonist and a glucagon-like peptide-1 receptor agonist. Trials of SGLT2i have had particularly important impact, as wide eligibility criteria in pivotal trials have enabled safety and efficacy across a wide range of causes of CKD to be demonstrated. These findings support the concept of final common pathways of CKD progression and should encourage similar trial designs recruiting broad ranges of patients at risk of CKD progression. This is important as these new drugs do not completely arrest CKD progression nor do they mitigate the full excess of cardiovascular disease. In the current era of multiple therapies to manage risk of CKD progression, trial design and conduct also need to consider new challenges. These include falling event rates, establishing standard of care for participants pre-randomization and improving the inclusion of trial participants understudied in previous trials. Streamlining trial design and conduct and reducing participation burden for patients and clinicians is increasingly important to facilitate larger sample sizes and to optimize adherence to study interventions and follow-up. Potential other solutions include maintaining a focus on wide generalizability (to include understudied patient groups) and empowering patients to volunteer for trials (through public and patient involvement and large-scale invitation methods), as well as innovations in trial design (including use of pre-randomization run-in periods to implement standard of care and factorial or platform trials to assess multiple treatments simultaneously).

Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) impact iron metabolism in patients with heart failure but mechanisms are incompletely understood. This post hoc analysis explored interrelations between iron homeostasis, cardiac structure/function, exercise capacity, haematopoiesis, and sympathetic activity at baseline, and the effects of 6-month treatment with empagliflozin vs. placebo by anaemia status in EMPATROPISM-FE study participants. Myocardial iron content (MIC, estimated by cardiac magnetic resonance T2* imaging), left ventricular (LV) volumes and LV ejection fraction (LVEF), exercise capacity, laboratory iron markers (LIM), haemoglobin/haematocrit, erythropoietin, and plasma norepinephrine were determined at baseline and 6 months. At baseline, 24/80 participants (30%) had anaemia (haemoglobin < 13/<12 mg/dL in men/women). Patients with vs. without anaemia had higher T2* (indicating lower MIC, P < .001), lower peak oxygen consumption (VO2max, P = .024) and hepcidin (P = .017), and higher erythropoietin (P = .040) and norepinephrine (P = .016). Across subgroups, lower MIC correlated with higher LV volumes (P < .01) and norepinephrine (P < .001), and lower LVEF (P < .01), VO2max (P < .001) and haemoglobin/haematocrit (P < .001). Associations with LIM were poor (all P > .10). Empagliflozin increased MIC (P < .012), improved exercise capacity, and activated haematopoiesis. Changes in LIM and norepinephrine suggested progressive systemic iron depletion and sympatholysis. LV reverse remodelling was greater in individuals with anaemia. Dysregulated cellular iron uptake/availability may be a shared mechanism in myocardial structural/functional impairment, reduced exercise capacity, and restricted haematopoiesis in heart failure, which are worse in patients with anaemia, and improve with empagliflozin. Empagliflozin increases MIC and decreases norepinephrine. Given this inverse association, sympatholysis may help explain the diverse cardiac and systemic benefits from SGLT2i therapy. NCT03485222 (www.clinicaltrials.gov).

A novel soluble guanylate cyclase activator, avenciguat, in combination with empagliflozin, protects against renal and hepatic injury in diabetic db/db mice.

Diabetic complications are linked to oxidative stress, which hampers the cyclic guanosine monophosphate production by inhibiting nitric oxide /soluble guanylate cyclase (sGC) signalling. This study aimed to determine whether administration of a novel sGC activator avenciguat alone or in combination with a SGLT2 inhibitor could slow the progression of renal and liver fibrosis in the type 2 diabetic and uninephrectomized db/db mouse model. Experiment groups included normal controls, untreated db/db mice terminated at 12 and 18 weeks of age, and db/db mice treated with either one of two doses of avenciguat alone, empagliflozin (Empa) alone, or a combination of both from weeks 12 to 18 of age. Untreated db/db mice exhibited obesity, hyperglycemia, elevated levels of HbA1c and triglycerides (TG) and developed progressive albuminuria, glomerulosclerosis, fatty liver and liver fibrosis between weeks 12 and 18 of age, accompanied by increased renal and liver production of fibronectin, type-IV collagen, laminin, and increased oxidative stress markers. Avenciguat had no effect on body weight but reduced both blood HbA1c and TG levels, while Empa reduced HbA1c but not TG levels as compared to untreated db/db. Both avenciguat and Empa alone effectively slowed the progression of diabetes-associated glomerulosclerosis and liver fibrosis. Importantly, avenciguat, especially at high dose in combination with Empa, further lowered these progression markers compared to baseline measurements. These results suggested that either avenciguat alone or in combination with Empa is therapeutic. Avenciguat in combination with Empa shows promise in halting the progression of diabetic complications.

Efficacy and safety of SGLT2 inhibitors in the treatment of maturity-onset diabetes of the young (MODY): a case report and literature review.

Sulfonylureas constitute the standard therapy for patients with HNF1A-MODY (maturity-onset diabetes of the young) but are characterized by an increased risk of hypoglycemia. While SGLT2 inhibitors (SGLT2i) may potentially represent a useful therapeutic option, data from the literature are scant. We report the case of a young woman affected by HNF1A-MODY who was successfully and safely treated with an SGLT2i in addition to sulfonylurea. After SGLT2i initiation, an improvement in the patient's glycemic control was observed and was maintained over time. No adverse effects were noted and, in particular, no increase in ketonemia or ketonuria occurred. The use of SGLT2i under controlled circumstances may represent a useful therapeutic option in patients with HNF1A-MODY.

Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling.

Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabetics and induces retinal angiogenesis. Mechanistic investigations demonstrate that HIF-1α directly regulates AGGF1 expression. AGGF1 upregulates the expression of cell cycle proteins by increasing the binding of tumour necrosis factor ligand superfamily member 12 (TNFSF12) to fibroblast -growth -factor-inducible 14 (FN14, TNFRSF12A). Furthermore, targeting AGGF1 attenuates pathological neovascularisation in ischaemic retinopathy. Additionally, we discover that sodium-glucose cotransporter 2 inhibitors (SGLT2i) could inhibit the AGGF1 signalling pathway early to achieve therapeutic effects. Overall, we elucidate the mechanism underlying pathological retinal angiogenesis involved in endothelial AGGF1-dependent events and highlight a therapy for the effective treatment of ischaemic retinopathy.

GLP-1 and SGLT2 Therapies in Type 2 Diabetes Mellitus. Cutting-Edge Approaches to Advancing Diabetes Care

Type 2 diabetes mellitus (T2DM) is a multifactorial disease characterized by insulin resistance, beta-cell dysfunction, and chronic hyperglycemia. Despite the availability of conventional therapies, significant unmet needs persist in achieving optimal glycemic control and reducing long-term complications. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors represent two novel classes of antidiabetic agents that have transformed the therapeutic landscape. This paper explores their mechanisms of action, clinical benefits, and potential synergistic effects, emphasizing their impact on cardiovascular and renal outcomes. Challenges and future directions for these agents in personalized diabetes care are also discussed.

Investigating the Relationship Between Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors and Blood Pressure.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors were originally approved for use in type 2 diabetes, but in recent years, these medications were found to also have significant cardiovascular benefits in patients with heart failure with reduced and preserved ejection fraction and chronic kidney disease. Part of the cardiovascular benefits of SGLT2 inhibitors likely comes from their antihypertensive effect in addition to other unknown effects, but the mechanism by which these medications reduce blood pressure has not been identified yet. Multiple mechanisms have been proposed to describe SGLT2 inhibitors' antihypertensive effect, including their associated weight loss and diuretic effect. However, studies have shown that these indirect mechanisms alone do not account for the antihypertensive effect seen with this medication, with more recent studies identifying a new potential mechanism by which SGLT2 inhibitors may derive their direct antihypertensive and cardiovascular benefits. In animal models, SGLT2 receptors were identified in parts of the brain responsible for regulating the sympathetic nervous system and adjusting blood pressure. In these studies, SGLT2 inhibitors suppressed the neuronal activity in these brain regions, reducing the sympathetic nervous system activity and blood pressure of the animals. Further investigation is needed to identify whether there are SGLT2 receptors in the central nervous system of humans and whether SGLT2 inhibitors can suppress neuronal activity in these brain regions. This information could be significant in learning more about the susceptibility and severity of primary hypertension in certain patient populations, as well as identifying whether SGLT2 inhibitors can be considered as a primary antihypertensive agent.

Effect of SGLT2i on kidney outcomes of individuals with type 2 diabetes according to body mass index: nationwide cohort study.

To investigate the clinical significance of the modification of the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors by baseline body mass index (BMI). We included individuals with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors newly prescribed for type 2 diabetes using a nationwide epidemiological cohort and performed propensity score matching (1:2). The primary outcome was the annual eGFR decline, assessed using a linear mixed-effects model, compared between individuals with SGLT2 inhibitors and DPP4 inhibitors. We investigated the interaction effect of BMI at the time of prescription using a three-knot restricted cubic spline model. We analysed 2165 individuals with SGLT2 inhibitor prescriptions and 4330 individuals with DPP4 inhibitor prescriptions. Overall, the annual decline in eGFR was less pronounced in the group treated with SGLT2 inhibitors than in those treated with DPP4 inhibitors (-1.34mL/min/1.73 m2 vs. -1.49mL/min/1.73 m2). The advantage of SGLT2 inhibitors in mitigating eGFR decline was augmented in the individuals with higher BMI (P-value for interaction 0.0017). Furthermore, even upon adjusting the definition of outcomes to encompass a 30 or 40% reduction in eGFR, the potential advantages of SGLT2 inhibitors over DPP4 inhibitors persisted, with a trend of augmented effects with higher BMI. This interaction effect was evident in the individuals with preserved kidney function. Our nationwide epidemiological study substantiated the improved kidney outcomes in the SGLT2 inhibitor users compared with the DPP4 inhibitor users across a wide range of BMI, which was pronounced for individuals with higher BMI.

Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors improve hyperglycemia, and SGLT2 inhibitors and GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACEs) among individuals with type 2 diabetes. It is not clear whether efficacy varies by age or sex. To assess whether age or sex are associated with differences in the efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP4 inhibitors. The MEDLINE and Embase databases and US and Chinese clinical trial registries were searched for articles published from inception to November 2022; in August 2024, the search was updated to capture the trial results. Two reviewers screened for randomized clinical trials of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP4 inhibitors vs a placebo or active comparator in adults with type 2 diabetes. Individual participant data and aggregate data were used to estimate age × treatment interactions and sex × treatment interactions in multilevel network meta-regression models. Hemoglobin A1c (HbA1c) and MACEs. Of the 601 eligible trials identified (592 trials with 309 503 participants reported HbA1c; mean age, 58.9 [SD, 10.8] years; 42.3% were female and 23 trials with 168 489 participants reported MACEs; mean age, 64.0 [SD, 8.6] years; 35.3% were female), individual participant data were obtained for 103 trials (103 reported HbA1c and 6 reported MACEs). The use of SGLT2 inhibitors (vs placebo) was associated with less HbA1c lowering with increasing age for monotherapy (absolute reduction [AR], 0.24% [95% credible interval {CrI}, 0.10% to 0.38%] per 30-year increment in age), for dual therapy (AR, 0.17% [95% CrI, 0.10% to 0.24%]), and for triple therapy (AR, 0.25% [95% CrI, 0.20% to 0.30%]). The use of GLP-1 receptor agonists was associated with greater HbA1c lowering with increasing age for monotherapy (AR, -0.18% [95% CrI, -0.31% to -0.05%] per 30-year increment in age) and for dual therapy (AR, -0.24% [95% CrI, -0.40% to -0.07%]), but not for triple therapy (AR, 0.04% [95% CrI, -0.02% to 0.11%]). The use of DPP4 inhibitors was associated with slightly better HbA1c lowering in older people for dual therapy (AR, -0.09% [95% CrI, -0.15% to -0.03%] per 30-year increment in age), but not for monotherapy (AR, -0.08% [95% CrI, -0.18% to 0.01%]) or triple therapy (AR, -0.01% [95% CrI, -0.06% to 0.05%]). The relative reduction in MACEs with use of SGLT2 inhibitors was greater in older vs younger participants per 30-year increment in age (hazard ratio, 0.76 [95% CrI, 0.62 to 0.93]), and the relative reduction in MACEs with use of GLP-1 receptor agonists was less in older vs younger participants (hazard ratio, 1.47 [95% CrI, 1.07 to 2.02]). There was no consistent evidence for sex × treatment interactions with use of SGLT2 inhibitors and GLP-1 receptor agonists. The SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower risk of MACEs. Analysis of age × treatment interactions suggested that SGLT2 inhibitors were more cardioprotective in older than in younger people despite smaller reductions in HbA1c; GLP-1 receptor agonists were more cardioprotective in younger people.

Understanding the disease: euglycemic ketoacidosis with SGLT2 inhibitors.

Understanding the disease: euglycemic ketoacidosis with SGLT2 inhibitors.

Prescription pattern, glycemic control status, and predictors of poor glycemic control among diabetic patients with comorbid chronic kidney disease in Ethiopia: a facility-based cross-sectional study

BackgroundAchieving optimal glycemic control is vital for managing diabetes mellitus and preventing its complications, yet it is particularly challenging for individuals with diabetes and concurrent chronic kidney disease. Chronic kidney disease disrupts glucose metabolism and excretion, leading to pronounced and variable blood glucose fluctuations, thereby complicating diabetes management. So far, the intricate impact of chronic kidney disease on the glycemic control status of diabetic patients remains obscure, especially in Sub-Saharan Africa where both diseases pose an escalating burden.ObjectiveThis study aimed to assess prescription patterns, glycemic control status, and the contributing factors to poor glycemic control among diabetic patients with comorbid chronic kidney disease at Tikur Anbessa Specialized Hospital, Ethiopia.MethodsA facility-based cross-sectional study was conducted from March 15 to May 15, 2024, from the electronic medical records of diabetic patients with comorbid chronic kidney disease who had received regular treatment and follow-up at the adult diabetes mellitus clinic of Tikur Anbessa Specialized Hospital. The sample size was calculated by using a single population proportion formula and accordingly, a total of 384 patients were recruited randomly and enrolled in this study. Descriptive statistics was employed for analyzing quantitative variables. Logistic regression analysis was performed to identify predictors of poor glycemic control status. Statistical significance was established at p-value < 0.05.ResultsThis study found that 98.2% of patients had type 2 diabetes, with a mean diabetes duration of 16.36 years. Only 4.4% achieved good glycemic control (glycated hemoglobin [HbA1c] < 7%), while 95.6% had poor glycemic control (HbA1c ≥ 7%). Insulin, metformin, and sodium glucose cotransporter-2 (SGLT-2) inhibitors were the most frequently prescribed anti-diabetic drug classes which accounted for 80.2%, 59.1%, and 41.4%, respectively. Presence of hypertension (AOR: 3.70, 95% CI: 1.08–12.71, P = 0.038) and regimen change in the past 01year (AOR: 0.34, 95% CI: 0.11–1.01, P = 0.050) were predictors of poor glycemic control status.ConclusionThis study reveals significant challenges in glycemic control among diabetic patients with comorbid chronic kidney disease (CKD). With only 4.4% of participants achieving optimal HbA1c levels, the findings underscore a critical public health concern regarding the management of diabetes in this vulnerable population.Clinical trial numberNot applicable.

Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigated. To assess the beneficial impact of SGLT2 inhibitors on VAs in patients at various stages of HF, a systematic review and meta-analysis of randomized controlled trials involving SGLT2 inhibitors in this patient population was performed.MethodsA comprehensive search of the PubMed, Embase, Ovid, ProQuest, Scopus, and Cochrane databases was performed for clinical trials published up to November 21, 2024. The primary outcomes of interest were incidences of VAs and sudden cardiac death (SCD) between the groups receiving SGLT2 inhibitors and the control drugs. For the outcomes observed in the populations of the included trials and in specific subgroups, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled and meta-analysed across the analyses.ResultsA total of 23 randomized trials (22 placebo-controlled trials and 1 active-controlled trial) involving 74,380 patients (37,372 receiving SGLT2 inhibitors and 37,008 in the control group) were included. The analysed SGLT2 inhibitors included canagliflozin, dapagliflozin, empagliflozin, bexagliflozin, sotagliflozin, and ertugliflozin. The participants were non-advanced HF patients, including at-risk for HF, pre-HF, and symptomatic HF, with follow-up duration ranging from 12 to 296 weeks. Compared with the control, treatment with SGLT2 inhibitors was associated with significantly reduced risk of VAs (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74–0.98; P = 0.02) and SCD (RR 0.79, 95% CI 0.64–0.98; P = 0.03). Subgroup analyses indicated that longer follow-up (≥ 1 year) taking SGLT2 inhibitors can still reduce the risk of VAs (RR 0.79, 95% CI 0.65–0.96; P = 0.02) and SCD (RR 0.80, 95% CI 0.65–0.99; P = 0.04).ConclusionSGLT2 inhibitors have beneficial effects on lowering risks of VAs and SCD in patients with type 2 diabetes, cardiovascular diseases, heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mildly reduced ejection fraction (HFmrEF), with longer follow-up duration reinforcing these findings. However, future prospective trials are needed to verify the effects of SGLT2 inhibitors on VAs and SCD.Systematic review registrationPROSPERO (CRD42024601914)

Canagliflozin reverses doxorubicin-induced cardiotoxicity via restoration of autophagic homeostasis

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been reported as successful for preventing doxorubicin (DOX) -induced cardiotoxicity (DIC), but the underlying mechanisms are elusive. This study aimed to determine whether canagliflozin, an SGLT2i, protects against DIC by regulation of autophagic flux in cardiomyocytes through a mechanism independent of SGLT2. The differentially expressed autophagy-related genes (ARGs) in DIC were analyzed. Neonatal rat cardiomyocytes (NRCMs), H9C2 rat cardiomyocytes or C57BL/6 mice were treated with canagliflozin or vehicle. The effects on cellular apoptosis and autophagy were investigated using qRT-PCR, western blotting and immunofluorescence. Additionally, cardiac function, myocardial fibrosis, and apoptosis of cardiomyocytes were also assessed in mice. The potential molecular targets of canagliflozin were identified through molecular docking analysis. A total of 26 differentially expressed ARGs were identified. Canagliflozin significantly activated autophagic flux and inhibited apoptosis of cardiomyocytes in both DOX-treated H9C2 rat cardiomyocytes and NRCMs. In a murine model of DIC, canagliflozin improved cardiac dysfunction by suppressing cardiac remodeling, fibrosis, and apoptosis. Moreover, canagliflozin promoted autophagy by enhancing SIRT1 levels and inhibiting the PI3K/Akt/mTOR signaling pathway. Immunofluorescence assays revealed that canagliflozin promoted the translocation of LC3 from the nucleus to the cytoplasm. Molecular docking analysis confirmed that canagliflozin has high affinity for targets associated with DIC. These findings suggest that canagliflozin protects cardiomyocytes from DOX-induced cell death by activating SIRT1, inhibiting the PI3K/Akt/mTOR pathway, and enhancing autophagic flux.

Treating chronic kidney disease in Danish primary care: results from the observational ATLAS study

ObjectivesTo describe the clinical characteristics, comorbidity, and medical treatment in a primary care population with chronic kidney disease (CKD). Additionally, to investigate how primary care physicians (PCPs) diagnose, manage and treat impaired kidney function, including uptake of cardio-renoprotective renin–angiotensin–aldosterone system inhibitors (RAASis) and sodium glucose co-transporter 2 inhibitors (SGLT2is).DesignAn observational study of CKD prevalence, treatment patterns and comorbidities in primary care based on patient record data combined with a questionnaire on diagnosis, management and treatment of impaired kidney function in a real-world, primary care setting.SettingIn all 128 primary care clinics in Denmark of 211 randomly invited and a quetionnaire completed by 125/128 participating PCPs.MethodsA computerized selection identified 12 random individuals with CKD per clinic with ≥ 2 measurements of eGFR < 60 mL/min/1.73 m2 or UACR > 30 mg/g within two years (N = 1 497). Pre-specified data collected from individual electronic health records included demographics, clinical variables, comorbidities, and relevant prescribed medications.ResultsOf the CKD study population (N = 1 497), 80% had hypertension, 32% diabetes (DM), 13% heart failure (HF), 59% no DM/HF. ACEis/ARBs were prescribed to 65%, statins to 56%, SGTL2is to 14%, and MRAs to 8% of all individuals. Treatment patterns differed between individuals with varying comorbidities, e.g., ACEis/ARBs usage was higher in DM (76%) or HF (74%) vs. no DM/HF (58%), as was statin usage (76% in DM vs. 45% in no DM/HF). SGTL2i usage in no DM/HF was low. Most PCPs identified CKD using eGFR < 60 mL/min/1.73 m2 (62%) or UACR > 30 mg/g (58%) and 62% reported initiating treatment to retard kidney function decline.ConclusionsDespite good PCP awareness and wish to use relevant guidelines, a gap exists in implementation of cardio-renoprotective treatment, especially in individuals without DM/HF. This offers an opportunity for clear recommendations to PCPs to optimize early cardio-renal protection in individuals with CKD.

Dapagliflozin alleviated seizures and cognition impairment in pilocarpine induced status epilepticus via suppressing microglia-mediated neuroinflammation and oxidative stress.

Status epilepticus (SE) is a neurological emergency with prolonged seizures leading to chronic epilepsy, cognitive impairment, and neuronal damage. Microglial activation, subsequent neuroinflammation and oxidative stress contribute to SE-induced neuronal injury. Single-cell sequencing has delineated the pro-inflammatory microenvironment in epileptic lesions, characterized by widespread microglial activation. Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), has shown potential in modulating neuroinflammatory responses. This study aimed to investigate the effects of Dapagliflozin on seizure and cognitive impairment by alleviating microglia-mediated neuroinflammation, oxidative stress. Single-Cell Transcriptomic Analysis were used to reveal SLC5A2 cellular heterogeneity and subtype-specific signatures of Temporal lobe Epilepsy. Male C57BL/6 mice were administered pilocarpine. Dapagliflozin were injected immediately after the termination of SE and at 24-hour intervals after SE until sacrifice. The latency and seizure score were recorded. Morris water maze were used to evaluate cognitive function of mouse. The neuroinflammation cell model was induced by lipopolysaccharide(LPS) in BV2 cell. Immunofluorescent staining, immunohistochemistry, flow cytometry, western blot, RT-qPCR, ELISA etc were used to examine the activation of microglia, evaluate neuroinflammation and oxidative stress. The expression of SLC5A2 is up-regulated in microglia of epileptic patients. Administration of Dapagliflozin significantly reduced seizure activity and improved cognitive performance in SE mouse. Dapagliflozin reduced microglial activation, as indicated by downregulation of CD86, iNOS expression and increased CD206, Arg-1 level. Dapagliflozin decreased oxidative stress, as evidenced by reduced levels of malondialdehyde (MDA), reactive oxygen species (ROS), increased superoxide dismutase (SOD) and Glutathione (GSH) activity. In addition, Dapagliflozin treatment can rescured the neuronal damage and suppressed the release of inflammatory cytokines such as IL-6, IL-18 and IL-1β. Our findings suggest that Dapagliflozin exerts neuroprotective effects by modulating microglia-mediated neuroinflammation and oxidative stress. The inhibition of SGLT2 may represent a novel therapeutic strategy for the treatment of SE and associated cognitive impairments.

Predictors of Use of Individual Insulin and GLP-1 RA Products Versus Fixed Ratio Insulin/GLP-1 RA Combinations in Medicare Beneficiaries.

Background: In 2022, federal law capped insulin product costs at $35 per month for Medicare prescription drug plan recipients. However, this law did not address the high costs of other antihyperglycemic medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with an average copay of $120 per month. Under the law, fixed-ratio insulin/GLP-1RA combination products are classified as "insulin products," making these effective medications more accessible to patients who might otherwise be unable to afford them. Patients may not be aware of the potential financial benefits of combination products, highlighting the need to identify those using them to better educate both patients and providers. Objectives: The primary objective was to identify predictors of use for the insulin/GLP-1RA combinations. The secondary objective was to determine if there was a difference in medication cost to patients between individual and combination product users and determine cost savings potential of switching. Design: This was a retrospective, observational cohort analysis. Setting: Prescription fill data were examined for antihyperglycemic medications filled between January 1, 2022, and December 31, 2022. Prescriptions were filled within one regional division of a large community-based pharmacy chain, encompassing 71 pharmacies within Kansas, Nebraska, and Missouri. Methods: This retrospective observational cohort analysis examined prescription fill data for antihyperglycemic medications for the calendar year 2022 across one regional division of a large community-based pharmacy chain. Included patients 65 years of age or older with a Medicare prescription drug plan, using any basal insulin and any GLP-1RA, including combinations, as well as metformin, with ≥ 80% proportion of days covered. Demographics, usage predictors, and cost differences were compared between patients using individual products and those using insulin/GLP-1RA combination products. Results: A total of 138 patients were analyzed. The use of insulin/GLP-1RA combination products was associated with increased likelihood of using sodium-glucose cotransporter-2 inhibitors (P = 0.022). Median annual out-of-pocket spending was significantly different between groups (P < 0.001), with most combination users paying more than $1,000 less per year than individual product users. Conclusion: Insulin/GLP-1RA combination products represent a cost-effective alternative to individual antidiabetic pharmacotherapy agents.

American Society for Gastrointestinal Endoscopy position statement on periendoscopic management of patients on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.

American Society for Gastrointestinal Endoscopy position statement on periendoscopic management of patients on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.

WCN25-3864 A Rare Case of Emphysematous Cystitis Linked to Early SGLT-2 Inhibitor Therapy in Diabetes

WCN25-3864 A Rare Case of Emphysematous Cystitis Linked to Early SGLT-2 Inhibitor Therapy in Diabetes

Short-term effects of empagliflozin on preventing contrast induced acute kidney injury in patients undergoing percutaneous coronary intervention, a randomised trial

Contrast-induced acute kidney injury (CI-AKI) is a prevalent cause of hospital-acquired renal impairment in patients undergoing intervention. Limited clinical trials explore SGLT2 inhibitors’ effects on CI-AKI. This study aimed to assess the short-term effect of empagliflozin- an SGLT2 inhibitor- in reducing CI-AKI incidence in PCI patients regardless of diabetes. This research conducted a double-blind randomized clinical trial involving 121 patients undergoing PCI referred to Ghaem Hospital, Mashhad, Iran from 2022 to 2023. Participants were randomly assigned to receive empagliflozin (10 mg daily) or a placebo, starting one day before PCI and continuing for two days post-procedure. Renal function parameters such as estimated glomerular filtration rate (eGFR), creatinine, cystatin C, and urea were evaluated. After the intervention, empagliflozin users exhibited a significant reduction in mean cystatin C levels compared to the placebo users across all age groups (< 50 years, 50–60 years, and > 60 years). Patients older than 60 showed significant improvements in mean changes of eGFR with empagliflozin. Patients with eGFR > 60 and 45 < eGFR < 60 had a significant increase in eGFR in the empagliflozin group. Mean changes in cystatin C levels were significantly reduced with empagliflozin in all eGFR levels (> 60, 45–60, and < 45). There was no significant difference in urea and creatinine levels between the two groups. Empagliflozin notably decreases CI-AKI incidence in PCI patients by improving renal function parameters such as eGFR and cystatin C. These benefits were observed across various age groups, particularly in middle-aged and elderly, and those with varying renal function levels.