Use Of Sodium-glucose Cotransporter-2 Inhibitors Research Articles

Impact of sodium-glucose cotransporter 2 inhibitor on recurrence and cardiovascular outcomes after catheter ablation for atrial fibrillation in patients with heart failure

BackgroundThe impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown. ObjectiveWe investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation. MethodsHF 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 on the basis of 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. ResultsDuring a total of 1315 person-years of follow-up, AF recurred 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 hazard ratio, 0.56; 95% CI, 0.43–0.74; P < .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 hazard ratio, 0.58; 95% CI, 0.41–0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups. ConclusionThe 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.

Focus on heart failure with preserved ejection fraction: from trials to the real world of the Friuli-Venezia Giulia Cardiovascular Observatory

Heart failure with preserved ejection fraction (HFpEF) has been for decades a nosological entity lacking specific therapy, with some even questioning its existence. Recently, targeted therapies have been introduced for specific, albeit rare, phenotypes such as Fabry disease, hypertrophic cardiomyopathy and amyloidosis. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally developed as anti-diabetic drugs, have fortuitously emerged as effective molecules in improving the prognosis for both patients with heart failure with reduced ejection fraction (HFrEF) and those with HFpEF, reducing heart failure exacerbations by almost a third. Although there are some epidemiological differences, depending on the country and the context analyzed, it is generally agreed that HFpEF is the most represented phenotype of heart failure, and its prevalence has been increasing in recent years due to the increase in life expectancy, improved diagnostic sensitivity and accuracy, and an exponential increase in risk factors such as diabetes, hypertension, renal failure, chronic obstructive pulmonary disease and obesity. These are often associated, turning out to be an epiphenomenon of a more complex cardio-nephro-metabolic disease. However, data and characteristics from major trials are not always aligned with the features and needs of these patients in real-world settings.The Cardiovascular Observatory of Friuli-Venezia Giulia is a powerful clinical governance tool that allows us to specifically characterize these patients, identifying and directing them towards the most appropriate diagnostic and therapeutic pathways, contributing significantly to improved prognosis and reduced expenditure paid by the National Health System.The use of SGLT2i in HFrEF patients is poised to match that of historic neurohormonal treatments, while, being the only class of drugs currently recommended by the international guidelines, they should even surpass them in HFpEF patients. However, given the high prevalence of HFpEF, it is unlikely for its treatment to be a prerogative of cardiologists alone. In this regard, it will be crucial in the near future to implement shared and integrated pathways with other medical specialists (internists, diabetologists, and nephrologists), and especially with general practitioners, who most frequently encounter these patients, to select the cases with greater complexity and potential for effective therapeutic intervention.

The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data

We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio= 0.56, 95% confidence interval [CI]= 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (nSGLT2i= 24,155; nDPP4i= 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio= 0.77, 95% CI= 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n4C= 57,779; nUK_Biobank= 165,430), we found little evidence to support the association of HbA1c with prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.

Gender Differences in the Clinical Profile of Sodium-Glucose Cotransporter-2 Inhibitor-Related Urinary Tract Infections.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a novel class of oral antidiabetic agents with proven cardiovascular and mortality benefits. By promoting glucosuria, SGLT2Is increase the risk of genital and urinary tract infections (UTIs), which remain uncomplicated in most cases. Comparative studies detailing the gender differences in the clinical profile of SGLT2I-related UTIs (SUTIs) are lacking. Hence, this study was designed to investigate the gender-related differences in the clinical profile of SUTIs. Methodology This prospective study enrolled 100 consecutive diabetes mellitus patients with UTI symptoms who were on SGLT2Is. In addition to collecting clinical details, patients were subjected to the following investigations: complete blood counts, urea, creatine, liver function, lipid components, urine analysis, urine culture, and ultrasonography. Results Females (n = 80) outnumbered males (n = 20). Although females were younger than males (53.68 ± 10.26 vs. 63.30 ± 10.75 years, p = 0.003), body mass index (29.84 ± 7.22 vs. 24.62 ± 3.10 kg/m2, p = 0.008) and waist circumference (103.01 ± 14.49 vs. 93.75 ± 4.50 cm, p = 0.109) were higher in females. About 22.5% of females had undergone hysterectomy. The mean duration of diabetes mellitus was longer in males (10.64 ± 6.74 vs. 7.78 ± 4.75 years), whereas the median duration of SGLT2I use (4 (interquartile range (IQR) = 1-12) vs. 3 (IQR = 2-4) months) and mean HbA1c levels were not different between the two groups. A greater proportion of males were complicated by retinopathy (55% vs. 15%) and proteinuria (65% vs. 17.5%), while neuropathy (85% vs. 71.25%) rates were similar. Overall, 35% of males had complicated UTIs (renal abscess, pyelonephritis, prostatic abscess) compared to only 3.75% of females (p = 0.001). Conclusions The majority of SUTIs are uncomplicated in females whereas in males one-third are complicated infections. Although females with SUTI had a higher prevalence of obesity and dyslipidemia, males had a longer duration of diabetes mellitus and higher retinopathy prevalence. Extreme caution should be exercised in patients at risk for SUTI before prescribing SGLT2I.

Disparities in Use of Novel Diabetes Medications by Insurance: A Nationally Representative Cohort Study.

Minority racial and ethnic populations have the highest prevalence of type 2 diabetes mellitus but lower use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra), novel medications that reduce morbidity and mortality. Observed disparities may be due to differences in insurance coverage, which have variable cost-sharing, prior authorization, and formulary restrictions that influence medication access. To assess whether racial/ethnic differences in SGLT2i and GLP1ra use differ by payer. Cross-sectional analysis of 2018 and 2019 Medical Expenditure Panel Survey data. Adults ≥ 18years old with diabetes. We defined insurance as private, Medicare, or Medicaid using ≥ 7months of coverage in the calendar year. We defined race/ethnicity as White (non-Hispanic) vs non-White (including Hispanic). The primary outcome was use of ≥ 1 SGLT2i or GLP1ra medication. We used multivariable logistic regression to assess the interaction between payer and race/ethnicity adjusted for cardiovascular, socioeconomic, and healthcare access factors. We included 4997 adults, representing 24.8 million US adults annually with diabetes (mean age 63.6years, 48.8%female, 38.8%non-White; 33.5% private insurance, 56.8% Medicare, 9.8% Medicaid). In our fully adjusted model, White individuals with private insurance had significantly more medication use versus non-White individuals (16.1% vs 8.3%, p < 0.001), which was similar for Medicare beneficiaries but more attenuated (14.7% vs 11.0%, p = 0.04). Medication rates were similar among Medicaid beneficiaries (10.0% vs 9.0%, p = 0.74). Racial/ethnic disparities in novel diabetes medications were the largest among those with private insurance. There was no disparity among Medicaid enrollees, but overall prescription rates were the lowest. Given that disparities vary considerably by payer, differences in insurance coverage may account for the observed disparities in SGLT2i and GLP1ra use. Future studies are needed to assess racial/ethnic differences in novel diabetes use by insurance formulary restrictions and out-of-pocket cost-sharing.

SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum

PurposeThis study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data. MethodsWe conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation. FindingsPrior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74–0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001). ImplicationsIn this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.

Associations of SGLT-2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM) and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over two years from HT initiation. After propensity score matching, 2,155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (HR 0.689, 95% CI 0.582-0.816; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations and all-cause mortality. Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Comparison over Time of Adverse Drug Reactions in Diabetes Patients Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

The prescription of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been increasing due to their additional benefits, including weight loss, cardioprotection and renoprotection. Accordingly, there are concerns about the potential rise in severe adverse drug reactions (ADRs), such as urinary tract infections, diabetic ketoacidosis, volume depletion, and hypoglycemia. The Society has announced recommendations on the proper use of SGLT2 inhibitors. We aimed to elucidate the recent occurrence of severe ADRs which need discontinuation of SGLT2 inhibitors or hospitalization. In this retrospective cohort study, we identified 391 diabetic patients who were prescribed SGLT2 inhibitors upon admission to our hospital between April 2017 and March 2023. Of these, 68 patients who discontinued SGLT2 inhibitors for reasons other than ADRs were excluded. Patients were classified into the 2017 group and the 2020 group based on the treatment period of SGLT2 inhibitors, and the occurrence of ADRs and patient backgrounds were compared between the two groups. A total of 323 eligible patients were identified. Discontinuations of SGLT2 inhibitors decreased in the 2020 group (p < 0.05). However, discontinuations due to frailty increased (p < 0.05). Hospitalization due to ADRs, specifically those due to urinary tract infections, diabetic ketoacidosis, or volume depletion, did not specifically decrease (p = 0.273). This study indicated that there has been some improvement in the awareness of the proper use of SGLT2 inhibitors and there is still a need to continue enlightenment activities.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data.

Background and Objectives: Peritoneal dialysis (PD) is a renal replacement therapy modality in which the dialysis dose can be individually adapted according to the patients' residual kidney function (RKF). RKF is a crucial factor for technique and patient survival. Pharmacological strategies aimed at slowing the loss of RKF in patients on PD are limited. Therefore, we aimed to assess the potential effects and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the preservation of RKF in patients with and without type 2 diabetes mellitus (T2DM) on PD during an average follow-up of 6 months. Materials and Methods: In this retrospective observational, single-center study on real-world data, we included patients from the Peritoneal Dialysis Unit of the Hospital General Universitario de Ciudad Real, who started treatment with SGLT-2 inhibitors during the period from December 2022 to December 2023. Data on analytical and clinical parameters, RKF, and peritoneal membrane transport function were retrospectively collected at months 0, 3, and 6. Results: Out of 31 patients in our unit, 16 prevalent patients initiated treatment with SGLT-2 inhibitors (13 empagliflozin and 3 dapagliflozin). A total of 62.5% were male and the mean age was 67.3 years. The baseline peritoneal ultrafiltration was higher in the non-diabetic patient (NDMP) group than in the diabetic patient (DMP) group. However, the residual diuresis volume, 24 h residual renal clearance rate of urea in urine, and 24 h proteinuria were higher in the DMP group than in the NDMP group. At the sixth month, patients in both groups preserved RKF and diuresis, with a trend towards a non-significant reduction in proteinuria and blood pressure. Only two patients of the DMP group presented adverse effects. Conclusions: The use of SGLT-2 inhibitors in our sample of patients with and without T2DM on PD appears to be safe and effective to preserve RKF.

Impact of sodium-glucose cotransporter-2 inhibitor use on peak VO2 in advanced heart failure patients.

Advanced heart failure (HF) is an epidemic that affects multiple organ systems with high morbidity and mortality rates despite optimal medical therapy (OMT) and remains the leading cause of hospitalizations in type 2 diabetes-related cardiovascular disease. The addition of sodium-glucose co-transporter inhibitors (SGLT2i) in treating these patients has seen improved mortality and hospital admission rates. As such, we felt it was important to investigate whether the use of SGLT2i improved functional capacity in patients with HF when compared to OMT by evaluating maximum oxygen consumption (peak VO2) using cardiopulmonary exercise testing (CPET). We found 94 heart failure patients between August 2020 and August 2021 who underwent CPET before and after treatment at Mayo Clinic in Florida. 50 patients received OMT and 44 received OMT and SGLT2i therapy. CPET results before and after were compared for each group. The baseline ejection fraction was not significantly different between groups, with the OMT group at 38% and the SGLT2i group at 33%, p = 0.10. OMT patients were found to have a significantly lower hemoglobin A1c of 5.7 (5.4-6.1) compared to those with SGLT2i therapy of 6.4 (5.8-7.1), p = 0.01. The baseline peak VO2 was 17.3 ml/kg/min (13.3-21.6) in the OMT group and 17.3 ml/kg/min (14.4-18.9) in the SGLT2i group, p = 0.18, not significantly different. The interesting finding is that the follow-up peak VO2 at one year for the OMT group was 17 ml/kg/min (13.3-21.6), which was not significantly different from the SGLT2i group peak VO2 of 17 ml/kg/min (14.6-19.6), p = 0.19. Our study is the first to compare before and after peak VO2 values of the OMT+SGLT2i group to the patient's own baseline and we found no significant improvement. Our single-center data shows no improvement in functional capacity after the addition of SGLT2i therapy to OMT in patients with advanced heart failure. Improved hospitalization and symptoms may be attributed to other numerous effects of SGLT2i such as volume management.

Medication adherence to sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists: A meta-analysis.

To perform a meta-analysis comparing real-world medication adherence to sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs). A systematic search of Medline and Embase was conducted through October 2023. To meet inclusion criteria, articles had to be published in full text form and directly compare medication adherence to SGLT2is versus GLP-1RAs in adults. Only studies evaluating real-world data and utilizing the proportion of days covered (PDC) to measure adherence were included. Non-adherence, defined as the proportion of patients with a PDC <80%, was the primary outcome. A subgroup analysis evaluating results among studies conducted in the United States was performed. We identified eight studies evaluating 205 103 patients for inclusion. The most common country from which the data was derived was the United States (n = 5 studies). Upon meta-analysis, we observed no difference in non-adherence (i.e. PDC <80%) to SGLT2is versus GLP-1RAs (relative risk = 0.86; 95% confidence interval = 0.72-1.02). In the analysis, including only US studies, SGLT2i use was associated with a 23% lower risk of non-adherence compared with GLP-1RA use (relative risk = 0.77; 95% confidence interval = 0.72-0.82). In this meta-analysis of eight studies that included approximately 200 000 patients, there was no difference in adherence to SGLT2is versus GLP-1RAs. However, SGLT2i use was associated with higher adherence when the analysis was limited to US studies.

Sodium-Glucose Cotransporter-2 Inhibitors Use in Patients with Reduced Kidney Function Hospitalized for Fluid Overload and Heart Failure: An Observational Study.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended in kidney disease and heart failure to reduce adverse clinical outcomes, but utilization can vary. To understand potential gaps in clinical practice and identify opportunities for improvement, we aimed to describe the prevalence and factors associated with SGLT2i prescription in patients with reduced kidney function hospitalized for fluid overload and/or heart failure. Single-center observational study of patients with reduced kidney function (eGFR 20-59 mL/min/1.73 m2) hospitalized for fluid overload or heart failure between January 2022 and December 2023. Data were retrieved from electronic medical records. The outcome was SGLT2i prescription at discharge. Potential variables affecting SGLT2i prescription were identified during stakeholder engagement and evaluated using multivariable logistic regression. Among 2,543 patients, the median age was 79 (71, 86) years and admission eGFR was 38.7 (28.4, 49.4) mL/min/1.73 m2. SGLT2i was prescribed to 630 (24.8%) patients at discharge. SGLT2i prescription at discharge was independently associated with cardiovascular disease (OR 1.76, 95% CI: 1.31-2.35), diabetes (OR 1.59, 95% CI: 1.19-2.14), fluid overload or heart failure as the primary discharge diagnosis (OR 1.71, 95% CI: 1.29-2.28), SGLT2i pre-hospitalization (OR 104.91, 95% CI: 63.22-174.08), RAS blocker (OR 2.1, 95% CI: 1.65-2.89), and higher eGFR (OR 1.01, 95% CI: 1.003-1.02) at discharge; but inversely associated with older age (OR 0.97, 95% CI: 0.96-0.98). SGLT2i prescription at discharge was suboptimal among patients with reduced kidney function hospitalized for fluid overload and/or heart failure, especially in older age and more severe kidney disease. Additionally, cardiovascular disease, diabetes, primary discharge diagnosis of fluid overload or heart failure, prior SGLT2i use, and concurrent RAS blocker at discharge were independently associated with SGLT2i prescription at discharge. Interventions are needed to increase clinicians' knowledge and overcome clinical inertia to increase SGLT2i use in patients with fluid overload and heart failure.

Incidence and progression of diabetic retinopathy in patients treated with glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A population-based cohort study.

Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

Dipeptidyl peptidase 4 inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists do not worsen diabetic macular edema

AimsThere are limited studies on dipeptidyl-peptidase 4 inhibitor (DPP-4i), sodium glucose cotransporter 2 inhibitor (SGLT2-i), and glucagon-like peptide 1 (GLP-1) receptor agonist use and occurrence of diabetic macular edema (DME). The objective of this study was to determine the association between DPP-4i, SGLT2-i, and GLP-1 receptor agonist use and occurrence of DME. MethodsProportional hazard models were used to evaluate the change in hazard of developing DME associated with DPP-4i, SGLT2-i, or GLP-1 receptor agonist use. Models accounted for age at DR diagnosis, DR severity (proliferative vs non-proliferative stage), time-weighted average of HbA1c level, sex, and self-reported race/ethnicity. A p-value ≤ 0.05 was considered statistically significant. ResultsThe hazard ratio of developing DME after diagnosis of DR was 1.2 (CI = 0.75 to 1.99; p = 0.43) for DPP-4i use, 0.93 (CI = 0.54 to 1.61; p = 0.81) for GLP-1 receptor agonist use, 0.82 (CI = 0.20 to 3.34; p = 0.78) for SGLT2-i use, 1.1 (CI = 0.75 to 1.59; p = 0.66) for any one medication use, 1.1 (CI = 0.62 to 2.09; p = 0.68) and for any two or more medications use. ConclusionsWe did not find an association between DPP-4i, SGLT2-i, or GLP-1 receptor agonist use and increased hazard of development of DME among patients with DR.

Relationship between sodium-glucose cotransporter 2 inhibitors and atrial fibrillation recurrence after pulmonary vein isolation in patients with type 2 diabetes and persistent atrial fibrillation.

The impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the postoperative recurrence of atrial fibrillation (AF) in patients with persistent AF undergoing an initial radiofrequency ablation is not yet established. The objective of this study is to assess the impact of SGLT2 inhibitors on the recurrence of AF after radiofrequency ablation in patients with type 2 diabetes complicated persistent AF. A total of 182 patients with type 2 diabetes and persistent AF, who underwent their first radiofrequency ablation for AF at our center, were enrolled and divided into two groups: the SGLT2 inhibitor group and the non-SGLT2 inhibitor group. The main outcome of the follow-up was the postoperative recurrence of AF. A total of 49 participants experienced AF recurrence. The use of SGLT2 inhibitors in patients with type 2 diabetes who underwent AF ablation was associated with a significantly lower risk of AF recurrence (adjusted hazard ratio: 0.65; 95% confidence interval: 0.28-0.83; p < .01). The use of SGLT2 inhibitors is associated with a decreased risk of arrhythmia recurrence after AF ablation in patients with type 2 diabetes complicated with persistent AF.

Kidney outcomes with SGLT2 inhibitor vs. DPP4 inhibitor use in older adults with diabetes.

While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. Using a nationwide claims database, we studied 6354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction<0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a≥20%, ≥ 30%, and≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged≥60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses.

Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.

Risk of Urogenital Bacterial Infection with Sodium-Glucose Cotransporter-2 Inhibitors: A Retrospective Cohort Study Using a Claims Database.

The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan. In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model. We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83-0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03-1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61-1.81). SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks.

SGLT2 inhibitor use in the management of feline diabetes mellitus.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.

CARDIOPROTECTIVE PROPERTIES OF SGLT2-INHIBITORS

Due to its high mortality rate, heart failure (HF) presents a substantial worldwide health burden that calls for efficient treatment approaches. Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) have become essential treatments for heart failure in all left ventricular ejection fraction (LVEF) levels. Their processes, which include enhanced metabolic efficiency and ventricular loading circumstances, present encouraging results. The effectiveness of SGLT2 inhibitors, dapagliflozin and empagliflozin, in lowering cardiovascular mortality and heart failure hospitalizations in heart failure patients with reduced, mildly reduced, and preserved ejection fraction has been shown in several clinical trials, including DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER. These results represent a revolutionary development in the treatment of HF, emphasizing the use of SGLT2 inhibitors in comprehensive treatments, regardless of renal function or diabetes state.