Impact Of SGLT2 Inhibitors Research Articles

Impact of SGLT2 Inhibitors on the Risk of Postoperative AKI

Impact of SGLT2 Inhibitors on the Risk of Postoperative AKI

V-110.1: The impact of SGLT2 inhibitors on clinical outcomes in kidney transplant recipients with post-transplant diabetes mellitus.

V-110.1: The impact of SGLT2 inhibitors on clinical outcomes in kidney transplant recipients with post-transplant diabetes mellitus.

Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data.

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19-0.82]) and glomerular filtration rate (HR 0.98 [0.98-0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16-0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study.

Impact of SGLT2 Inhibitors on Atrial Fibrillation Recurrence after Catheter Ablation in Type 2 Diabetes Mellitus: A Meta-Analysis of Reconstructed Kaplan-Meier Curves with Trial Sequential Analysis.

The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in managing cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is evolving. This meta-analysis seeks to explore the influence of SGLT2i on the recurrence of atrial fibrillation (AF) following catheter ablation (CA) in individuals with T2DM qualitatively and quantitatively. A comprehensive literature search was conducted in electronic databases. Studies meeting predefined criteria were included. Individual patient data (IPD) were used from reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals for AF recurrence. IPD meta-analysis was followed by a direct meta-analysis to assess the risk of AF recurrence. A total of five studies [one randomized controlled trial (RCT) and four cohort studies] were included in this study, and five studies were included in the qualitative analysis, while four studies comprising 1043 patients with T2DM were included in the quantitative analysis. The pooled Kaplan-Meier curve based on reconstructed data showed a significantly lower risk of AF recurrence in the SGLT2i group compared with all antidiabetic drugs (log-rank P = 0.00011) and dipeptidyl-peptidase IV inhibitors (DPP4i) (log-rank P = 0.01). Cox regression analysis showed consistent results. Direct meta-analysis showed that SGLT2i, compared with all antidiabetic medications (HR 0.57, 95% CI [0.44, 0.73], I2) and DPP4i (HR 0.41, 95% CI [0.24, 0.70], I2), was associated with a lower risk of AF recurrence. SGLT2i are associated with a reduced risk of AF recurrence after CA in patients with T2DM. These results suggest that SGLT2i is promising in improving clinical outcomes for this population.

Impact of SGLT2 Inhibitors on Renal Function in Type 2 Diabetic Patients with Coronary Artery Disease Undergoing Percutaneous Intervention: A Systematic Review and Meta-Analysis.

Contrast agents directly cause kidney toxicity in patients undergoing Percutaneous Intervention for cardiovascular disease with Type 2 diabetes. This meta-analysis aims to evaluate the effects of SGLT2-i on renal function in individuals undergoing Percutaneous Intervention. The databases used for the search included PubMed, Scopus, Cochrane Central Registry of Controlled Trials, and Google Scholar. We considered Randomized controlled trials and observational studies published from January 2013 to August 2023. The eligibility to include the studies was assessed independently. The Cochrane modified data extraction form, and Joanna Briggs Institute was used. The Cochrane risk of bias tool and Newcastle-Ottawa quality assessment scale were used to assess the quality of the studies. The certainty of the evidence was assessed using GradePro software. The pooled estimate showed a substantial reduction in serum creatinine levels at 48- and 72-hours post-PCI who received SGLT2i (MD -9.57; 95% CI -18.36, -0.78; p-value 0.03) and (MD -14.40; 95% CI -28.57, -0.22; p-value 0.05). There was a decrease in the incidence of the CI-AKI among SGT2i users (RR: 0.46; 95% CI: 0.32, 0.67; p value< 0.0001). There was no significant difference in the number of patients requiring hemodialysis, but a smaller number of patients required hemodialysis among the SGLT2i users (RR: 0.88; 95% CI: 0.19, 4.07; p-value = 0.87). The use of SGLT2i confers substantial beneficial effects on kidney function and reduction of incidence of Contrast-induced acute kidney injury among patients undergoing PCI procedures for cardiovascular disease with diabetes.

A-23 | Impact of SGLT-2 Inhibitors on intra-hospital length of stay after Acute Myocardial Infarction in Patients with Type II Diabetes Mellitus treated with PCI

A-23 | Impact of SGLT-2 Inhibitors on intra-hospital length of stay after Acute Myocardial Infarction in Patients with Type II Diabetes Mellitus treated with PCI

A-24 | Impact of SGLT-2 Inhibitors on Mortality after Acute Myocardial Infarction in Patients with Type II Diabetes Mellitus treated with PCI

A-24 | Impact of SGLT-2 Inhibitors on Mortality after Acute Myocardial Infarction in Patients with Type II Diabetes Mellitus treated with PCI

Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

BackgroundSodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been widely taken into consideration. But there are controversial results in the study on the effect of SGLT2 inhibitors on bone metabolism in patients with T2DM. Therefore, we aimed to examine whether and to what extent SGLT2 inhibitors affect bone metabolism in patients with T2DM.MethodsA literature search of randomized controlled trials (RCTs) was conducted through PubMed, Web of Science, Embase, Cochrane databases, and Scopus from inception until 15 April 2023. Eligible RCTs compared the effects of SGLT2 inhibitors versus placebo on bone mineral density and bone metabolism in patients with T2DM. To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences (SMD).ResultsThrough screening, 25 articles were finally included, covering 22,828 patients. The results showed that, compared with placebo, SGLT2 inhibitors significantly increased parathyroid hormone (PTH, SMD = 0.13; 95%CI: 0.06, 0.20), and cross-linked C-terminal telopeptides of type I collagen (CTX, SMD = 0.11; 95%CI: 0.01, 0.21) in patients with T2DM, decreased serum alkaline phosphatase levels (ALP, SMD = -0.06; 95%CI: -0.10, -0.03), and had no significant effect on bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxy vitamin D, tartrate resistant acid phosphatase-5b (TRACP-5b) and osteocalcin.ConclusionsSGLT2 inhibitors may negatively affect bone metabolism by increasing serum PTH, CTX, and decreasing serum ALP. This conclusion needs to be verified by more studies due to the limited number and quality of included studies.Systematic review registrationPROSPERO, identifier CRD42023410701

Impact of SGLT-2 inhibitors on modifiable cardiovascular risk factors in Romanian patients with type 2 diabetes mellitus.

Modifiable cardiovascular risk factors are high blood pressure, smoking, diabetes, sedentary lifestyle, obesity, and hypercholesterolemia. To investigate the impact of sodium-glucose 2 co-transporter inhibitors (SGLT-2i) on modifiable cardiovascular risk factors in Romanian patients diagnosed with type 2 diabetes mellitus (T2DM). A retrospective study was conducted on 200 Romanian patients with T2DM who were being treated with SGLT-2i, either Dapagliflozin or Empagliflozin. Collected data included demographic characteristics, such as weight, body mass index (BMI), fasting blood glucose (FBG), creatinine, glycated hemoglobin (HbA1c), abdominal circumference (AC), urine albumin-to-creatinine ratio (UACR), systolic blood pressure (SBP), diastolic blood pressure (DBP), C-reactive protein (CRP) and N-terminal pro b-type natriuretic peptide (NT-proBNP). The patients were observed for one year after being treated with SGLT-2i. The mean value of FBG decreased from 180.00mg% (IQR: 154.50-207.00) to 130.00mg% (IQR: 117.50-150.00) (p < 0.001), and the mean of HbA1c values decreased from 8.40% (IQR: 7.98-9.15%) to 7.30% (IQR: 6.90-7.95%) (p < 0.001). We also obtained significant positive effects on body weight, i.e., the weight decreased from 90.50kg (82.00-106.50) to 89.00kg (77.50-100.00) (p = 0.018), BMI from 32.87kg/m2 (29.24-36.45) to 31.00kg/m2 (27.74-34.71) (p < 0.001) and AC from 107.05 (± 16.39) to 102.50 (± 15.11) (p = 0.042). The UACR decreased from 23.98mg/g (19.76-36.85) to 19.39mg/g (1.30-24.29) (p < 0.001). Initially, the median value for SBP was 140.00mmgHg (130.00-160.00), and for DBP was 80.00 mmgHg (72.00-90.00), and one year after treatment, the medium value was 120.00 mmgHg (115.50-130.00) for SBP (p < 0.001), and 72.00 mmgHg (70.00-78.00) for DBP (p < 0.001) The mean CRP values decreased from 68.00mg/dL (56.25-80.25) to 34.00mg/dL (28.12-40.12) (p < 0.001), and the mean NT-proBNP decreased from 146.00pg/mL (122.50-170.50) to 136.00 pg/mL (112.50-160.50) (p = 0.005). Treatment with SGLT-2i in Romanian patients with T2DM has beneficial effects on modifiable cardiovascular risk factors.

Impact of SGLT2 inhibitors on erythropoiesis and iron exchange in patients with diabetes mellitus and chronic heart failure

Impact of SGLT2 inhibitors on erythropoiesis and iron exchange in patients with diabetes mellitus and chronic heart failure

Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction: data from SGLT2-I AMI PROTECT Registry

Abstract Background Diabetes patients presenting with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have an increased risk of contrast induced-acute kidney injury (CI-AKI). It has been shown that SGLT2-I have a nephroprotective effect. Purpose To analyze the association between SGLT2-I treatment and the development of contrast-induced acute kidney injury (CI-AKI) in diabetic patients with AMI (both ST- and non-ST segment elevation myocardial infarction - STEMI and NSTEMI) treated with PCI. Methods In this multicenter international registry, all consecutive diabetic AMI patients undergoing PCI between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, they were divided into SGLT-I users versus non-SGLT2-I users. All patients had estimated glomerular filtration rate (eGFR) of &amp;gt;30 mL/min/1.73 m2. No patient discontinued SGLT2-I during hospitalization. Serum creatinine was collected at admission and within 72 h post-PCI. CI-AKI was defined as absolute (≥0.5 mg/dl) or relative increase (≥25%) in serum creatinine at 48-72 h after PCI compared to baseline serum creatinine values. Results The study population consisted of 646 AMI patients: 111 SGLT2-I users and 535 non-SGLT-I users. The mean age of the overall study population was 70 [61-79] years, and more than 77% were males. The mean T2DM duration was similar for both groups. SGLT2-I patients were younger and with better renal function at admission compared to non-SGLT2-I users (p&amp;lt;0.018 for both). Gender, cardiovascular risk factors, glucose-metabolic control, and comorbidities were similar in the two groups. The rate of STEMI and the main angiographic characteristics were similar between the two study groups, except for the higher number of stents implanted in the SGLT2-I group (p=0.041). Vascular access and contrast dosage did not differ between the 2 cohorts. A similar rate of complete revascularization, staged procedure and complex PCI was observed between the study groups. After PCI, the overall rate of CI-AKI was 76 (11.8%). SGLT2-I users exhibit a lower rate of CI-AKI compared to non-SGLT-I ones (5.4% vs 13.1%, p=0.02), with significantly lower creatinine values both after PCI (p=0.016) and at discharge (p=0.046). At multivariate analysis, after adjusting for all confounding factors, the use of SGLT2-I was identified as independent predictor of reduced rate of CI-AKI (OR 0.374; 95% CI 0.142-0.987, p=0.040). During a median follow-up of 24±13 months, patients with CI-AKI showed a higher incidence of MACE compared to patients without (44.7% vs 25.8%, p=0.001). Conclusion In diabetic patients with AMI, the use of SGLT2-I was associated with a lower risk of CI-AKI during index hospitalization, providing new insights into the cardioprotective effects of SGLT2-I in the setting of AMI.

Impact of SGLT2 inhibitors on contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions

Impact of SGLT2 inhibitors on contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions

Impact of SGLT2 Inhibitors on Corneal Nerve Morphology and Dendritic Cell Density in Type 2 Diabetes

ABSTRACT Purpose This study aims to determine the effects of SGLT2 inhibitors on corneal dendritic cell density and corneal nerve measures in type 2 diabetes. Methods Corneal dendritic cell densities and nerve parameters were measured in people with type 2 diabetes treated with SGLT2 inhibitors (T2DM-SGLT2i) [n = 23] and those not treated with SGLT2 inhibitors (T2DM-no SGLT2i) [n = 23], along with 24 age and sex-matched healthy controls. Results There was a reduction in all corneal nerve parameters in type 2 diabetes groups compared to healthy controls (All parameters: p < 0.05). No significant differences in corneal nerve parameters were observed between T2DM-SGLT2i and T2DM-no SGLT2i groups (All parameters: p > 0.05). Central corneal dendritic cells were significantly reduced [mature (p = 0.03), immature (p = 0.06) and total (p = 0.002)] in the T2DM-SGLT2i group compared to the T2DM-no SGLT2i group. Significantly, higher mature (p = 0.04), immature (p = 0.004), total (p = 0.002) dendritic cell densities in the T2DM-no SGLT2i group were observed compared to the healthy controls. In the inferior whorl, no significant difference in immature (p = 0.27) and total dendritic cell densities (p = 0.16) between T2DM-SGLT2i and T2DM-no SGLT2i were observed except mature dendritic cell density (p = 0.018). No differences in total dendritic cell density were observed in the central (p > 0.09) and inferior whorl (p = 0.88) between T2DM-SGLT2i and healthy controls. Conclusion The present study showed a reduced dendritic cell density in people with type 2 diabetes taking SGLT2 inhibitors compared to those not taking these medications.

Effect of sodium-glucose transporter 2 inhibitors on bone

Diabetes mellitus is a common illness, and the number of people affected by this condition is expected to increase significantly. Complications associated with type 2 diabetes mellitus, such as cataracts, retinopathy, neuropathy, and orthostatic hypotension, can increase the risk of falls and subsequent bone fractures. Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and ipragliflozin are a group of medications known as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which are oral drugs used to treat type 2 diabetes mellitus. This group of medications is a recent addition to the current treatment options for this condition. There are concerns about the impact of SGLT-2 inhibitors on bone health. Although drugs in this category have similarities in reducing blood glucose and preventing cardiovascular disease, they can have varying effects on bone metabolism. The effect of SGLT-2 inhibitors (SGLT-2is)-induced weight loss on bone mineral density (BMD) and bone turnover is significant and cannot be disregarded. Although SGLT-2 inhibitors were initially predicted to increase the likelihood of bone fractures, clinical evidence contradicts this assumption. It is noteworthy to emphasize that empagliflozin and dapagliflozin did not indicate an increased risk of fractures. It is also interesting to note that SGLT2i drugs positively affect heart function and can reduce the incidence of heart failure, which can lead to a decrease in osteoporosis and bone fractures. Based on clinical trials and real-world evidence, there does not appear to be a link between the administration of SGLT2 inhibitors and the risk of fractures. However, caution should still be exercised when prescribing these drugs to patients with advanced disease or kidney complications who may be at higher risk of bone fractures. It is always important to consider individual patient factors and potential risks before making treatment decisions.

Impact of SGLT2 Inhibitors on AF Recurrence After Catheter Ablation in Patients With Type 2 Diabetes

BackgroundThe effects of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on recurrent atrial fibrillation (AF) among patients undergoing catheter ablation is not well described. ObjectivesThis study sought to assess the impact of SGLT2-Is on the recurrence of AF among patients with type 2 diabetes mellitus (DM) after catheter ablation. MethodsUsing the TriNetX research network, we identified, by means of Current Procedural Terminology codes, patients ≥18 years of age with type 2 diabetes mellitus (DM) who had undergone AF ablation from April 1, 2014, to November 30, 2021. Patients were stratified based on the baseline SGLT2-I use. Propensity-score matching resulted in 2,225 patients in each cohort. The primary outcome was a composite of cardioversion, new antiarrhythmic drug (AAD) therapy, or re-do AF ablation after a blanking period after the index ablation. Additional outcomes included heart failure exacerbations, ischemic stroke, all-cause hospitalization, and death during 12 months of follow-up. ResultsSGLT2-I use in patients with type 2 DM undergoing AF ablation was associated with a significantly lower risk of cardioversion, new AAD therapy, and re-do AF ablation (adjusted OR: 0.68; 95% CI: 0.602-0.776; P < 0.0001). At 12 months, patients on SGLT2-Is had a higher probability of event-free survival (HR: 0.85, 95% CI: 0.77-0.95; log-rank test chi-square = 8.7; P = 0.003). All secondary outcomes were lower in the SGLT2I group; however, the ischemic stroke did not differ between groups. ConclusionsUse of SGLT2-Is in patients with type 2 DM is associated with a lower risk of arrhythmia recurrence after AF ablation and thence a reduced need for cardioversion, AAD therapy, or re-do AF ablation.

SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: Meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type

Background and aimsSodium glucose co-transporter 2 (SGLT2)-inhibitors were developed as glucose-lowering drugs. Surprisingly, SGLT2-inhibitors also reduced risk of cardiovascular disease. The impact of SGLT2-inhibitors on lipids and lipoproteins is unclear, but an effect might contribute to the observed lower cardiovascular risk. We conducted a meta-analysis to examine this, overall and by dose, ethnicity, and drug type. MethodsPubMed, EMBASE and Web of Science were searched for randomized controlled trials examining all available SGLT2-inhibitors. Studies with available lipid measurements were included. Quantitative data synthesis was performed using random and fixed effects models. ResultsWe identified 60 randomized trials, including 147,130 individuals. Overall, using random effects models, SGLT2-inhibitor treatment increased total cholesterol by 0.09 mmol/L (95% CI: 0.06, 0.13), low-density lipoprotein (LDL) cholesterol by 0.08 mmol/L (0.05, 0.10), and high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (0.05, 0.07), while it reduced triglycerides by 0.10 mmol/L (0.06, 0.14). Fixed effects estimates were similar but with smaller effect sizes for HDL cholesterol and triglycerides. For higher SGLT2-inhibitor doses, there was a nominally higher non-significant effect on lipids and lipoproteins. In Asian compared to non-Asian populations, a slightly larger increase in HDL cholesterol and a decrease in triglycerides were observed, but with similar results for total and LDL cholesterol. Treatment effects on lipids and lipoproteins were generally robust across different SGLT2-inhibitor drugs. ConclusionIn meta-analyses, SGLT2-inhibition increased total, LDL, and HDL cholesterol and decreased triglycerides. Effect sizes varied slightly by drug dose and ethnicity but were generally robust by drug type.

500-P: Causal Effect of SGLT2 Inhibition on Diabetes-Related Retinopathy (DR) and Macular Edema (DME)

Background: SGLT2 inhibitors have been shown to slow cardiac and renal disease progression. Currently, there is limited literature on the impact of SGLT2 inhibitors on DR and more specifically DME. Objective: Evaluate the effect of SGLT2 inhibitors on central subfoveal thickness (CST) in patients with T2D and on the need and frequency of intravitreal injections (IVI) for DME. Methods: A retrospective matched cohort study with propensity score matching to reduce confounding and determine treatment effect. Covariates: age, sex, type of DM, last A1c, level of retinopathy, insurance, IVI, Visual Acuity (VA). Treatment: SGLT2i use. Primary Outcome: CST on Optical Coherence Tomography (OCT). Secondary Outcomes: IVI use and frequency for DME. By ICD-10 codes 10,026 patients were found to have diabetes and were seen in 2021 at Retina Associates, LLC Kansas City. Retrospectively screened 1,000 consecutive patient medical records from this cohort and included those with T2D and on an SGLT2i. We excluded those with incomplete records, T1D, and those who had a second diagnosis that could cause macular edema. Results: 321 patients had DR; 280 with T2D of which 71 were on an SGLT2i and included for analysis. Baseline cohort characteristics: mean age (SD): 62.2 yr (11.4); 58.9% were male; 76.1% White, 11.1% Black, 6.8% Hispanic/Latino; 13.2% used tobacco; 75.4% had HTN; last recorded A1C 7.6 (1.6); Visual Acuity in ETDRS letters OD: 74.1 (12.9) OS: 73.8 (14.7); CST OD: 279.9 (56.6) OS: 279.6 (54.7). Comparing CST and the need for IVI to those not on an SGLT2i the CST OD/OS was 280.1 (32)/280.3 (36.3) vs 279.9 (62.8)/279.4 (59.7) and 40.8% vs 36.8% required IVI with a risk ratio of 1.13 and a risk difference of 0.03 and p-value of 0.55 95% CI [-0.07, 0.14]. After Propensity Score Matching: ATE risk difference was 0.04 and a p-value of 0.37 and 95% CI [-0.05, 0.14]. Conclusions: No positive or negative effect on mean CST or difference in the average treatment effect for DME was found for those taking an SGLT2 inhibitor. Disclosure H.Stevens: None. J.M.Breen: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.

Impact of SGLT2 inhibitors on the mechanisms of myocardial dysfunction in type 2 diabetes: A prospective non-randomized observational study in patients with type 2 diabetes mellitus without overt heart disease

AimsThis prospective observational study evaluated the possible mechanisms of action of SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) without overt heart disease. MethodsThe study was designed to verify whether SGLT2i impact biomarkers of: myocardial stress–NT-proBNP, inflammation–high sensitivity C-reactive protein, oxidative stress –myeloperoxidase, functional and structural echocardiographic parameters, in patients with T2DM on metformin (heart failure stages A and B) who needed treatment intensification with a second antidiabetic agent. The patients were divided in two groups – the ones planned to receive SGLT2i or DPP-4 inhibitor (except saxagliptin). At baseline, and after six months of therapy, 64 patients underwent blood analysis, physical and echocardiography examination. ResultsThere were no significant differences between the two groups in terms of biomarkers of myocyte and oxidative stress, inflammation and blood pressure. Body mass index, triglycerides, aspartate aminotransferase, uric acid, E/E′, deceleration time and systolic pressure in the pulmonary artery significantly decreased, while stroke volume, indexed stroke volume, high-density lipoprotein, hematocrit and hemoglobin significantly increased in the group on SGLT2i. ConclusionsAccording to the results, SGLT2i mechanisms of action comprise rapid changes in body composition and metabolic parameters, reduced cardiac load and improvement in diastolic and systolic parameters.

Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction with and without chronic kidney disease: Insight from SGLT2-I AMI PROTECT registry

AimsTo analyze the association between chronic SGLT2-I treatment and development of contrast-induced acute kidney injury (CI-AKI) in diabetic patients with acute myocardial infarction (AMI) undergoing PCI. MethodsMulticenter international registry of consecutive patients with type 2 diabetes mellitus (T2DM) and AMI undergoing PCI between 2018 and 2021. The study population was stratified by the presence of chronic kidney disease (CKD) and anti-diabetic therapy at admission (SGLT2-I versus non-SGLT2-I users). ResultsThe study population consisted of 646 patients: 111 SGLT2-I users [28 (25.2%) with CKD] and 535 non-SGLT2-I users [221 (41.3%) with CKD]. The median age was 70 [61–79] years. SGLT2-I users exhibited significantly lower creatinine values at 72 h after PCI, both in the non-CKD and CKD stratum. The overall rate of CI-AKI was 76 (11.8%), significantly lower in SGLT2-I users compared to non-SGLT2-I patients (5.4% vs 13.1%, p = 0.022). This finding was also confirmed in patients without CKD (p = 0.040). In the CKD cohort, SGLT2-I users maintained significantly lower creatinine values at discharge. The use of SGLT2-I was an independent predictor of reduced rate of CI-AKI (OR 0.356; 95%CI 0.134–0.943, p = 0.038). ConclusionIn T2DM patients with AMI, the use of SGLT2-I was associated with a lower risk of CI-AKI, mostly in patients without CKD.

The impact of SGLT2 inhibitors on αKlotho in renal MDCK and HK-2 cells.

αKlotho is a transmembrane protein predominantly expressed in the kidney serving as a co-receptor for phosphate homeostasis-regulating hormone FGF23 and has an extracellular domain that can be cleaved off and is a hormone. αKlotho deficiency results in accelerated aging and early onset of aging-associated diseases while its overexpression strongly expands the lifespan of mice. Moreover, αKlotho exerts health-beneficial anti-inflammatory, anti-neoplastic, anti-fibrotic, and anti-oxidant effects. Higher αKlotho levels are associated with better outcomes in renal and cardiovascular diseases. SGLT2 inhibitors are novel drugs in the treatment of diabetes by inhibiting renal glucose transport and have additional nephro- and cardioprotective effects. We explored whether SGLT2 inhibitors affect αKlotho gene expression and protein secretion. Experiments were performed in renal MDCK and HK-2 cells, and αKlotho transcripts were determined by qRT-PCR and Klotho protein by ELISA. SGLT2 inhibitors canagliflozin, sotagliflozin, and dapagliflozin enhanced whereas empagliflozin reduced αKlotho gene expression in MDCK cells. By the same token, canagliflozin, sotagliflozin, dapagliflozin, but not empagliflozin down-regulated p65 subunit of pro-inflammatory NFκB. In HK-2 cells, all SGLT2 inhibitors reduced αKlotho transcripts. Canagliflozin and sotagliflozin, however, increased Klotho protein concentration in the cell culture supernatant, an effect paralleled by up-regulation of ADAM17. Taken together, our investigations demonstrate complex effects of different SGLT2 inhibitors on αKlotho gene expression and protein secretion in renal MDCK and HK-2 cells.