The clinical effective of sodium/glucose co-transporter-2 inhibitors on admission frequency, duration and use of acute non-invasive ventilation in patients with chronic obstructive pulmonary disease: A single-centre 24-month retrospective observational study in a UK tertiary care centre

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to acute exacerbations, cardiovascular disease, and premature death. To compare the risk of COPD exacerbation, cardiovascular diseases, and mortality between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and no use in patients with type 2 diabetes mellitus (T2DM) and COPD. The study included 299,168 patients diagnosed with T2DM and COPD in the National Health Insurance Research Database from January 1, 2009, to December 31, 2020. Cox proportional hazards models were used to examine the relative hazard of major adverse cardiovascular events, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation, lung cancer, and mortality between SGLT-2 inhibitor users and nonusers. We used propensity score matching to select 1288 pairs of SGLT-2 inhibitor users and nonusers. In the matched cohorts, SGLT-2 inhibitor use was associated with a significantly lower risk of mortality (aHR 0.64, 95% CI 0.43-0.95), NIPPV (aHR 0.48, 95% CI 0.27-0.87), and hospitalization for COPD (aHR 0.82, 95% CI 0.69-0.98) than SGLT-2 inhibitor non-use. Subgroup and dose-response analyses showed that SGLT-2 inhibitor use was associated with a significantly lower risk of mortality, NIPPV, and hospitalization for COPD (p<0.05) than no use of SGLT-2 inhibitors. This population-based cohort study showed that SGLT-2 inhibitors use was associated with a lower risk of COPD exacerbations, ventilator support, and mortality than non- SGLT-2 inhibitors use in patients with T2DM and COPD. SGLT-2 inhibitors may have a role in treating patients with COPD and diabetes.

Sodium-glucose co-transporter 2 inhibitors for heart failure: clinical trial efficacy and clinical practice effectiveness.

Comparison of SGLT2 and DPP4 inhibitors on clinical outcomes in COPD patients with diabetes: A nationwide cohort study.

Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus

CE-452774-3 SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITOR USE IN TYPE II DIABETES MELLITUS IS ASSOCIATED WITH A LOWER RATE OF ATRIAL ARRHYTHMIAS IN A REAL-WORLD POPULATION

The impact of sodium-glucose co-transporter 2 inhibitors on the incidence of non-tuberculous mycobacteria infection in diabetes populations.

Identifying Barriers To SGLT2 Inhibitor Use In Eligible Patients With Heart Failure: A Real-world Experience From A Single Centre

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been suggested to exert anti-inflammatory effects in the gastrointestinal tract based on preclinical and observational studies. Whether these effects translate into a reduced risk of inflammatory bowel disease (IBD), compared with other antidiabetic agents of similar therapeutic rank, remains unclear. This study aims to evaluate the association between SGLT-2i use and the risk of IBD in patients with type 2 diabetes mellitus (T2DM), using dipeptidyl peptidase-4 inhibitors (DPP-4i) as an active comparator. A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database from 2016 to 2022. Patients with T2DM who initiated SGLT-2i or DPP-4i therapy were included. Propensity score matching (1:4) was performed based on key covariates. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated for incident IBD, including its subtypes ulcerative colitis (UC) and Crohn's disease (CD), using Cox proportional hazards models and Fine and Gray competing risk models (considering death as a competing event), with further adjustment for residual confounding. Sensitivity analyses were conducted using alternative induction periods and several on-treatment approaches that accounted for treatment discontinuation. Among 258,355 patients (51,671 SGLT-2i users and 206,684 DPP-4i users), the incidence of IBD was lower in the SGLT-2i group (12.51 vs. 35.83 per 100,000 person-years). SGLT-2i use was associated with a significantly reduced risk of IBD (aHR: 0.391; 95% CI 0.237-0.645; p < 0.001), with consistent results across multiple sensitivity analyses. In this nationwide real-world cohort, SGLT-2i use was associated with a lower risk of IBD compared with DPP-4i among patients with T2DM. These findings suggest potential gut-protective effects of SGLT-2i and support their consideration in clinical decision-making for patients at elevated risk of IBD. Further prospective studies are warranted to validate these observations and elucidate the underlying mechanisms.

The association between the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and the occurrence of drug-induced kidney injury has not been evaluated. This study assessed whether the use of SGLT-2 inhibitors decreases the risk of drug-induced acute kidney injury (AKI) using the US Food and Drug Administration's Adverse Event Reporting System and the Medical Data Vision database. The occurrence of AKI in SGLT-2 inhibitor users and dipeptidyl peptidase-4 (DPP-4) inhibitor users was compared using both databases. In the US Food and Drug Administration's Adverse Event Reporting System analysis, disproportionality for AKI was observed between DPP-4 inhibitor users and SGLT-2 inhibitor users administered nonsteroidal anti-inflammatory drugs (reporting odds ratio, 0.65; 95%CI, 0.48-0.88; P < .01) and thiazide diuretics (reporting odds ratio, 0.78; 95%CI, 0.67-0.90; P < .01). In Medical Data Vision analysis, SGLT-2 inhibitor users administered nonsteroidal anti-inflammatory drugs (odds ratio [OR], 0.46; 95%CI, 0.41-0.53; P < .01), anti-herpes simplex virus drugs (OR, 0.20; 95%CI, 0.07-0.53; P < .01), thiazide diuretics (OR, 0.50; 95%CI, 0.36-0.71, P < .01), and loop diuretics (OR, 0.71; 95%CI, 0.62-0.83; P < .01) had a lower incidence of AKI compared with DPP-4 inhibitor users receiving the same drugs. No differences were observed in the risk of AKI between SGLT-2 and DPP-4 inhibitor users administered vancomycin and cisplatin in both databases. The use of SGLT-2 inhibitors might reduce the risk of drug-induced AKI caused by some drugs.

BackgroundThere is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan.MethodsThe patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.ResultsAmong 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan–Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant β-blocker, diuretics, or insulin.ConclusionThe use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence.

BackgroundAcute kidney injury (AKI) following transcatheter aortic valve implantation (TAVI) is associated with significantly worse outcomes, leading to increased short- and long-term mortality. We sought to evaluate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the risk of AKI in patients with type 2 diabetes mellitus (T2DM) and severe aortic stenosis (AS) undergoing TAVI.MethodsMulticenter international registry of consecutive T2DM patients with severe AS undergoing TAVI between 2021 and 2024. The study population was stratified by the presence of chronic kidney disease (CKD), defined according to the KDIGO guideline, and anti-diabetic therapy at hospital admission (SGLT2i versus no-SGLT2i users). AKI was defined according to the Valve Academy Research Consortium 3 (VARC-3) criteria.ResultsThe study population consisted of 514 patients stratified into those without CKD (n = 226, 44%), of whom 43 (19%) were treated with SGLT2i, and 288 (56%) with CKD, of whom 71 (24.7%) were on SGLT2i treatment. The median age was 81 [77–84] years, and 60.1% were males. SGLT2i use did not impact renal function in patients without CKD, with AKI occurring in 7.1% of the cases, regardless of SGLT2i use. Among CKD patients, AKI occurred more frequently in no-SGLT2i users compared to those receiving SGLT2i (19.8% versus 8.5%, p = 0.027), with a significant increase in post-TAVI and discharge serum creatinine values for no-SGLT2i users (p = 0.001 after TAVI and p < 0.001 at hospital discharge). Only in the CKD group, the use of SGLT2i was identified as an independent predictor of a lower rate of AKI (OR 0.70, 95%CI 0.42–0.91, p = 0.014). Patients who developed AKI had a higher incidence of major adverse cardiovascular events during follow-up, regardless of CKD (p < 0.025 for both groups).ConclusionIn diabetic patients with CKD undergoing TAVI, SGLT2i therapy was associated with a lower occurrence of AKI compared to those not treated with SGLT2i, suggesting a potential nephroprotective effect in this high-risk population.Graphical abstractSummary of the main findings of the study.

Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new-onset overall cancer and pre-specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium-glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I. This population-based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong. This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all-cause mortality (HR: 0.92; 95% CI: 0.84-0.99; p= 0.04), cancer-related mortality (HR: 0.58; 95% CI: 0.42-0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59-0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new-onset breast cancer (HR: 0.51; 95% CI: 0.32-0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64-0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43-0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27-0.83; p = 0.001). Sodium-glucose cotransporter 2 inhibitor use was associated with lower risks of all-cause mortality, cancer-related mortality and new-onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.

To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective cohort study by analysing a large multi-institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61-81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4-108.7] mL/min/1.73 m2 and urine albumin-creatinine ratio [UACR] 26.1 [9.7-117.6] mg/g) and 1067 new users of GLP-1RAs (mean [SD] age 58.4(41.5) years, median [IQR] HbA1c 73 [64-84] mmol/mol, eGFR 91.6 [68.6-114.0] mL/min/1.73 m2 and UACR 37.6 [11.1-153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person-years), compared to those receiving GLP-1RAs (10.7/1000 person-years) with an HR of 0.75 (95% CI 0.64-0.88). Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP-1RAs. Future studies are necessary to confirm this observation.

To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28599 patients (mean age 60±11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10586 were new users of SGLT2 inhibitors and 18013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.

Objective To assess the association between the use of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and the incidence of diabetic retinopathy (DR). Research design and methods PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were searched from inception to October 2021. Randomized controlled trials (RCTs) with reports of incidence of DR and other eye disorders between SGLT2i and non-SGLT2i users with type 2 diabetes mellitus were included. Results In general, the incidences of DR were comparable between SGLT2i and non-SGLT2i users (OR = 0.80, 95%CI 0.61 to 1.06, P = 0.12). However, compared with non-SGLT2i users, the incidence of DR was significantly reduced in SGLT2i users with diabetes duration less than 10 years (OR = 0.32, 95%CI 0.13 to 0.76, P = 0.01). Weight reduction in SGLT2i users was associated with a decreased risk of retinal detachment. Moreover, longer study duration was associated with lower incidence of cataract and retinal vasculopathy in SGLT2i users. Conclusions In general, the use of SGLT2i was not associated with the incidence of DR. However, a reduced risk of DR was observed in SGLT2i users with diabetes duration less than 10 years. An early initiation of SGLT2i might be more likely to provide with ocular benefits.