Sodium-glucose Cotransporter 2 Inhibitor Group Research Articles

Cardiovascular protective effect of sodium-glucose cotransporter 2 inhibitors on patients with acute coronary syndrome and type 2 diabetes mellitus: a retrospective study

BackgroundAcute coronary syndrome (ACS) remains the leading cause of death and disability worldwide, especially when combined with type 2 diabetes mellitus (T2DM). Many multicenter randomized controlled trials have established the cardiovascular benefits of Sodium-Glucose cotransporter 2 inhibitors (SGLT-2i) in patients with T2DM at high cardiovascular risk. However, these studies did not include patients in the early stages of acute coronary events. This study investigated the cardiovascular protective effects of SGLT-2i in patients with ACS and T2DM.MethodsA total of 232 hospitalized patients with ACS and T2DM were enrolled and divided into two groups based on their hypoglycemic drug treatment: the SGLT-2i and the non-SGLT-2i groups. Kaplan–Meier analysis and Cox regression were used to compare adverse cardiovascular outcomes in both groups.ResultsThere were no significant differences in the hospital clinical outcomes between the SGLT-2i and non-SGLT-2i groups. The adverse cardiovascular outcomes did not significantly differ between both groups (hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.35–1.25, P = 0.195). Moreover, the rehospitalization rates for ACS or heart failure (HF) were not significantly different between both groups (adjusted HR 0.56, 95%CI 0.28–1.10, P = 0.093). When analyzed separately, there was no significant difference in rehospitalizations for ACS (HR 0.87, 95% CI 0.40–1.87, P = 0.713). However, the SGLT-2i group showed lower rates of rehospitalizations for HF (adjusted HR 0.20, 95% CI 0.04–0.96, P = 0.045). Additionally, there was no significant difference in cardiovascular mortality between both groups (HR 1.75, 95% CI 0.28–10.97, P = 0.543). Notably, the SGLT-2i group exhibited a higher angina symptom control rate than the non-SGLT-2i group (adjusted odd ration (OR) 0.45, 95%CI 0.21–0.93, P = 0.031).ConclusionIn recently diagnosed patients with ACS, who have T2DM, early initiation of SGLT-2i was associated with a lower risk of rehospitalization for HF and a higher rate of angina symptom control.

Clinical outcomes with the use of sodium-glucose cotransporter-2 inhibitors in patients with atrial fibrillation and type 2 diabetes mellitus: a multi-centre, real-world cohort study.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular outcomes and reduce the incidence of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We investigated the clinical outcomes with and without the use of SGLT2is in patients with T2DM and concomitant AF. We derived patient data from a clinical data warehouse constructed from the electronic medical records of seven medical centres. Data for 11 012 patients diagnosed with both AF and T2DM were analysed. New SGLT2i users were classified into the SGLT2i group and those who were not prescribed SGLT2is were classified into the control group. We performed a 1:2 propensity score (PS)-matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure (HF) events in 3 years. The PS-matched population consisted of 1115 patients in the SGLT2i group and 2050 patients in the control group. Incidence of the primary endpoint was significantly lower in the SGLT2i group [8.4 vs. 14.6%, hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.55-0.87]. Sodium-glucose cotransporter-2 inhibitors use was associated with significantly lower all-cause mortality (HR 0.43, 95% CI 0.29-0.67) and HF hospitalization (HR 0.77, 95% CI 0.59-0.99). Adverse renal events, defined as >50% increase in serum creatinine level or initiation of dialysis, occurred less often in the SGLT2i group (HR 0.50, 95% CI 0.38-0.66, P < 0.001). Use of SGLT2is in patients with T2DM and concomitant AF was associated with reduced mortality or HF hospitalization events.

THU287 Comparison Of Renal Protective Effects Between SGLT2 Inhibitors And DPP4 Inhibitors In Real-World Clinical Practice

Abstract Disclosure: H. Park: None. S. Park: None. S. Kwon: None. H. Kim: None. D. Byun: None. Recent prospective randomized studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors had renal protective effects compared to placebo. In this study, we compared the renal composite outcomes between patients with diabetes treated with SGLT2 inhibitors and those treated with dipeptidyl peptidase 4 (DPP4) inhibitors using real-world clinical data. This retrospective observational study used the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database at four different university hospitals (Soonchunhyang university hospitals in Seoul, Bucheon, Chunan, and Gumi) in Korea. Subjects prescribed SGLT2 inhibitors or DPP4 inhibitors for at least 90 days were included in the SGLT2 inhibitor or DPP4 inhibitor group, respectively. Subjects prescribed GLP-1 receptor agonist or insulin were excluded in both groups. Renal composite outcomes included a 30% decline in estimated glomerular filtration rate (eGFR) compared to baseline or creatinine doubling or dialysis or death from any cause. After propensity score matching, clinical characteristics in each group at each hospital were well balanced at baseline. Our results from hospitals in Seoul, Bucheon, and Gumi have shown that SGLT2 inhibitor decreased renal composite outcomes compared to DPP4 inhibitor (hazard ratio (HR) 0.644, p=0.020; HR 0.560, p&amp;lt;0.001; HR 0.657, p=0.010, respectively). Furthermore, when all the data were combined, renal composite outcomes were significantly lower in the SGLT2 inhibitor group compared to the DPP4 inhibitor group (HR 0.659, p&amp;lt;0.001). In conclusion, SGLT2 inhibitors effectively reduce renal composite outcomes compared to DPP4 inhibitors in real-world clinical practice. Presentation: Thursday, June 15, 2023

THU282 Improved Fournier’s Gangrene Outcomes With Prior SGLT2i Or Metformin Usage

Abstract Disclosure: S. Venugopal: None. S. Patel: None. Z. Wu: None. F. Galbiati: None. J. Oh: None. P. Manroa: None. E. Morariu: None. M. Stefanovic-Racic: None. Introduction: Fournier’s gangrene (FG) is a rare, necrotizing fasciitis of the external genitalia with high mortality up to 30% that is more prevalent in males, diabetes, HIV, and immunocompromised states. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been linked with FG. Interestingly, multiple studies have found no significantly increased risk of FG with SGLT2i use. However, these studies have very large confidence intervals due to the rarity of the observed event. Methods: A retrospective study between 3/1/2013-6/12/2020 was performed at four different tertiary hospitals within the University of Pittsburgh Medical Center (UPMC) system to compare the severity and outcome of FG between type 2 diabetes patients who were treated with SGLT2is, metformin, and insulin prior to admission. Results: 202 patients were admitted for FG (8 on SGLT2is, 80 on Metformin, and 88 on insulin). Baseline characteristics such as age, sex, and HbA1c were generally similar. Duration of diabetes was longer in subjects on insulin vs not on insulin (p&amp;lt;0.001). Creatinine(Cr) on admission was lower in SGLT2i vs not on SGLT2i (p=0.056) and metformin vs not on metformin (p=0.037), but was higher in the insulin vs non-insulin group (p=0.004). The SGLT2i group had a shorter hospital stay (p=0.045), a lower rate of ICU admission (p=0.0093), and a trend toward a shorter ICU stay than the non-SGLT2i group (p=0.053). In the metformin group, the cases of amputation were lower compared to the non-metformin group (p=0.026). In the insulin group, there was a trend toward a longer hospital stay (p=0.057) and ICU stay (p=0.052) vs the non-insulin group. Conclusion: The use of SGLT2i does not appear to worsen the clinical course or outcome of FG and may actually improve it based on our data showing decreased ICU admissions and length of stay. Metformin usage may dampen the severity of FG by significantly decreasing cases of amputation. Noteworthy is that Cr was lower in the SGLT2i and metformin groups. Further analysis of baseline characteristics such as renal function, HbA1c, and duration of diabetes will determine whether they may affect the severity of FG. Presentation: Thursday, June 15, 2023

SAT671 SGLT2 Inhibition Decreases Adipose Tissue And Global Inflammaging Profile Of Older Obese Adults With Pre-Diabetes

Abstract Disclosure: J. Nie: None. M.K. Semwal: None. F.M. Acosta: None. A.R. Stepanenko: None. M. Brown: None. A.J. Moody: None. N. Sanchez: None. T.M. Cortes: None. Y. Qin: None. C. Triplitt: None. G. Clarke: None. S.E. Espinoza: None. N. Musi: None. C. Solis-Herrera: None. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are drugs for treating T2D. Through their glucosuric effect, you see a reduced HbA1c, weight loss, and improved insulin sensitivity/ β-cell function. Beyond their glycemic properties, SGLT2i provide substantial cardio-renal benefits. Given their multiple therapeutic advantages and established safety profile, there is the presupposition that SGLT2i may have various beneficial possibilities in medical practice. An area of interest for SGLT2i is their use as agents for late-aging and longevity. SGLT2i are known to promote a calorie restriction (CR) state by promoting glucosuria and fatty acid-oxidation/ketogenesis and reducing insulin levels. CR activates a myriad of anti-aging-related pathways, including senescence-associated “inflammaging,” which can be triggered by obesity and states of overnutrition. However, clinical research in this area remains largely unexplored. A single-center, open-label, randomized-controlled clinical trial was designed to determine the effect of SGLT2i on the aging-related processes of global and adipose tissue inflammation and senescence. Twenty older, obese, pre-diabetic subjects (Age=70±1.5, BMI=33.7±0.6, A1c=5.9±0.03) were randomized dapagliflozin 10mg/day (SGLT2i) vs. nutritional counseling for weight loss (control) in a 1:1 fashion for 12 weeks. Healthspan and clinical evaluation were performed at baseline and weeks 10-12 of the study. The SGLT2i group showed a significant decrease (-5.4±1.7, p=0.01) in weight loss, downward trend in HbA1c (-0.02±0.06 vs. +0.06±0.04), and significant loss in %Fat vs. control (-1%, p=0.05 vs. -0.5%, p=0.1). Given adiposity changes observed with SGLT2i, in a subset of subjects (n=10), subcutaneous fat biopsies were performed, and single nuclei (sn)RNA-seq done to map changes in adipose cellular populations (mature adipocytes, immune, endothelial, and adipogenic progenitor cells) and molecular profiling. Notably, with SGLT2i, the mature adipocyte, immune, and adipogenic progenitor cells, saw a significant (p≤0.05) decrease in senescent score. Globally, plasma-measured inflammaging-associated factors in the IL8 and TNFα families, also saw a significant decrease (p≤0.05) with SGLT2i.Aging and metabolic homeostasis are bidirectional processes. As you age, adiposity tends to increase, associated with an upsurge in the development of metabolic syndrome-related diseases in older adults. Here we demonstrate that in the high-risk population of older obese adults with pre-diabetes, SGLT2i targets multiple points in the spectrum that delay the aging process. In particular, we show evidence that SGLT2i treatment improves the global and adipose senescent and inflammatory profile, alongside glycemic and weight control. These findings support the notion that SGLT2i may contribute to the increase of both healthspan and lifespan. Presentation: Saturday, June 17, 2023

Renoprotective potential of concomittant medications with SGLT2 inhibitors and renin-angiotensin system inhibitors in diabetic nephropathy without albuminuria: a retrospective cohort study

The renal protective effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors and renin-angiotensin system (RAS) inhibitors on diabetic nephropathy without albuminuria have not been fully investigated. This retrospective cohort study focused on patients with type 2 diabetes mellitus who had a baseline estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2, and a urinary albumin-to-creatinine ratio < 30 mg/gCr. After propensity score matching, using covariates such as age, body mass index, systolic blood pressure, hemoglobin A1c levels, and prescription history of RAS inhibitors, we established a cohort of 58 patients: the SGLT2 inhibitor group (n = 28) and the control group (n = 28). In this cohort, we compared the annual eGFR decline rate between the two groups. The SGLT2 inhibitor group exhibited a significantly smaller eGFR change than the control group (− 1.15 vs. − 2.18 mL/min/1.73 m2/year). Within the SGLT2 inhibitor group, patients prescribed RAS inhibitors had demonstrated an even smaller eGFR change (− 0.70 mL/min/1.73 m2/year). In conclusion, SGLT2 inhibitors also have safeguarding effects in the stage of diabetic nephropathy without albuminuria, and the combined use of a SGLT2 inhibitor and a RAS inhibitor appears to be more effective than the single use of each.

Sodium-glucose co-transporter 2 inhibitors & glucagon-like peptide-1 receptor agonists, efficacy & safety in diabetic kidney transplant recipients.

Cardiovascular and renal complications define the outcomes of diabetic kidney transplant recipients (KTRs). The new diabetes medications have changed the management of diabetes. However, transplant physicians are still reluctant to use sodium-glucose cotransporter 2 inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) post kidney transplantation due to fear of drug related complications and lack of established guidelines. We collected 1-year follow-up data from records of 98 diabetic KTRs on SGLT2I, 41 on GLP- 1RA and 70 on standard-of-care medicines. Patients were more than 3 months post-transplant with a minimum estimated glomerular filtration rate (eGFR) of 25ml/min/1.73m2 . Demographic data were similar except for a slightly lower HbA1c in the control group and higher albuminuria in SGLT2i group. HbA1c dropped significantly by .4% in both SGLT2i and GLP-1RA compared to .05% in the control group. A significant decrease in BMI by .32 in SGLT2i and .34 in GLP-1RA was observed compared to an increase by .015 in control group. A tendency for better eGFR in study groups was observed but was non-significant except for the SGLT2i group with an eGFR above 90 (p=.0135). The usual dip in eGFR was observed in the SGLT2i group at 1-3 months. Albuminuria was significantly reduced in both study groups. Adverse events were minimal with comparable safety in all groups. The use of SGLT2i and GLP-1RA appears to be effective and safe in diabetic KTRs with good outcomes. Randomized control trials are required to confirm these findings and establish guidelines.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis.

Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients. We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects. Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was - 141.34mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo. For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.

Impact of sacubitril/valsartan and gliflozins on cardiac resynchronization therapy response in ischemic and non-ischemic heart failure patients

AimsAngiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose co-transporter 2 inhibitor (SGLT2i) improve outcomes in heart failure with reduced ejection fraction (HFrEF) patients, however their effects in cardiac resynchronization therapy (CRT) recipients have been scarcely explored. This study investigated whether ARNi and SGLT2i 1) improve the rate of clinical and echocardiographic CRT response and 2) have different impact based on the ischemic or non-ischemic etiology. MethodsHFrEF patients referred for CRT implant were grouped in no treatment (group 1), only ARNi (group 2) and both ARNi and SGLT2i (group 3). Clinical and echocardiographic response were evaluated at 12 months. ResultsA total of 178 patients were enrolled. At one-year follow-up, 74.4% patients in group 2 (p = 0.031) and 88.9% in group 3 (p = 0.014) were classified as clinical responders vs 54.5% in the no treatments group. In multivariable analysis, ARNi/SGLT2i use was an independent predictor of CRT response (OR 3.72; CI 95%, 1.40–10.98; p = 0.011), confirmed in both groups 2 and 3. At 12 months, the median Δ LVEF increase was 6% and 8.5% in groups 2 and 3 respectively, vs 4.5% in group 1 (p = 0.042 and p = 0.029) with significantly more echocardiographic responders in groups 2 and 3 (76% and 78% vs 50%, p = 0.003 and p = 0.036). Significantly more ischemic HFrEF patients than non-ischemic were considered clinical and echocardiographic responders in the treatment groups. ConclusionsARNi alone or in combination with SGLT2i in CRT patients improves the clinical and echocardiographic response at 12 months. Ischemic patients seem to benefit more from these treatments.

Effect of sodium-glucose cotransporter 2 inhibitors on left atrial remodeling and prognosis in patients with type 2 diabetes and heart failure with reduced ejection fraction.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been found to minimize hospitalization for heart failure and cardiovascular death. Cardiac reverse remodeling may be a mechanism responsible for the favorable clinical efficacy of SGLT2is on heart failure. To date, few studies have examined their effects on the left atrium. Therefore, the purpose of this study was to explore whether SGLT2is improve left atrial adverse remodeling in patients with type 2 diabetes and heart failure with reduced ejection fraction (HFrEF). A single-center, retrospective, observational study was conducted. Consecutive patients with type 2 diabetes and HFrEF hospitalized at the First Affiliated Hospital of Dalian Medical University for acute decompensated heart failure between 1 January 2019 and 1 March 2022 were identified. On the basis of their treatment strategies, the enrolled participants were classified into SGLT2i and non-SGLT2i groups. The primary end point was all-cause mortality. Changes in left atrial echocardiographic indices from baseline to follow-up were also assessed. A total of 198 patients (mean age: 63.96 ± 12.11 years, 20.71% women) were included. Greater reductions from baseline were seen with SGLT2i in the left atrial diameter (P < 0.001), left atrial superior-inferior diameter (P = 0.027), left atrial transverse diameter (P = 0.020), left atrial volume (P = 0.005), and left atrial volume index (P = 0.004). Moreover, 48 cases (48.48%) in the SGLT2i group and 33 (33.33%) in the non-SGLT2i group showed left atrial reverse remodeling (P = 0.003). Survival analysis demonstrated significantly lower overall mortality in the SGLT2i group compared with the non-SGLT2i group. This study found that SGLT2i therapy promoted left atrial structure reverse remodeling. This beneficial effect may be a vital mechanism by which SGLT2i improved clinical outcomes in patients with HFrEF.

Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in bridge-to-transplant patients supported with centrifugal-flow left ventricular assist devices

BackgroundThe safety and tolerability of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with end-stage heart failure supported with left-ventricular-assist-devices (LVADs), irrespective of diabetes mellitus, is not known. MethodsA retrospective analysis of 31 outpatients implanted with LVADs as bridge-to-transplant (BTT) was conducted. Patients with biventricular support, aged under 18 years, who were discharged from the index hospitalisation, or were prescribed SGLT2i prior to their first outpatient clinic were excluded. Patient demographics, laboratory studies, pump haemodynamic and adverse event data was collected. ResultsSixteen (51.6%) of 31 patients were prescribed SGLT2i over median 101.5 days (37.5–190.8). No patients discontinued SGLT2i use or reported attributable adverse symptoms. No significant differences between patients prescribed SGLT2i compared to those SGLT2i-naïve were seen in: [1] renal function; [2] weight; [3] mean arterial pressure. There were numerically lower infection-related (n = 4 vs 7, HR 0.32 (0.08–1.28), p = 0.11) and haemocompatibility-related (n = 3 vs 4, HR 0.52 (0.09–2.83), p = 0.45) adverse events in the SGLT2i group, albeit non-significant. ConclusionsWe found SGLT2i to be safe and well-tolerated in the BTT LVAD cohort with no significant difference in rates of infection or haemocompatibility-related adverse events with SGLT2i use. Larger studies will inform further beneficial effects of SGLT2i prescription in this cohort.

Real-world risk of cardiovascular diseases in patients with type 2 diabetes associated with sodium-glucose cotransporter 2 inhibitors in comparison with metformin: A propensity score-matched model analysis in Japan.

We aimed to compare the effects of cardiovascular disease risk in Japanese patients with type 2 diabetes on sodium-glucose cotransporter 2 inhibitors (SGLT2Is) or metformin. This retrospective, real-world cohort study was carried out using a claims database and propensity score matching; 58,402 eligible patients (29,201 per group) were included. The outcomes included nonfatal myocardial infarction, angina pectoris, nonfatal stroke, hospitalization for heart failure and composite end-points. The hazard ratio (HR) for the composite end-point was 0.79, which was lower for SGLT2Is than for metformin. For male patients (HR 0.76), patients aged <65 years (HR 0.94), patients aged ≥75 years (HR 0.78) and patients with body mass index ≥25 kg/m2 (HR 0.76), the HRs for the composite end-point were significantly lower in the SGLT2I group than in the metformin group. SGLT2Is might be superior to metformin in reducing the composite risk of cardiovascular disease in patients with type 2 diabetes.

Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus

BackgroundAlthough sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI.MethodsThis study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed.ResultsAfter IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio [HR], 0.99; 95% confidence interval [Cl], 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027).ConclusionsOur findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction.Trial registrationNot applicable (retrospectively registered).

Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation.

Background Whether the early use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose-lowering drugs were matched based on a propensity score. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all-cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow-up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54-0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60-0.99]; P=0.04). All-cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all-cause mortality, hospitalizations for heart failure, and major adverse cardiac events.

Exploring the comparative cardiovascular death benefits of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a frequentist and Bayesian network meta-analysis-based scoring.

Cardiovascular death (CV death) is the most objective component of the primary or secondary endpoint in cardiovascular outcome trials (CVOTs) conducted with sodium-glucose cotransporter 2 inhibitors (SGLT-2is). CV death is often incorporated into primary composite outcomes. It is combined with major adverse cardiovascular events (MACEs) in trials with atherosclerotic cardiovascular disease (ASCVD) at baseline and with hospitalization due to heart failure (hHF) in trials with heart failure at baseline. Unlike the primary composites, CV death reduction by itself demonstrated significant variations among the CVOTs with SGLT-2is. Moreover, the impact of the individual agents within the SGLT-2i group on the reduction in CV death has not been explored objectively. This network meta-analysis was undertaken to construct a hierarchy based on indirect pairwise comparisons and rankings among the individual agents within SGLT-2is. A Cochrane library-based web search yielded 13 randomized controlled trials for analysis. Stata/BE 17.0 and RStudio 2022.07.1 Build 554 software were used to conduct a frequentist and Bayesian network meta-analysis. The effect size was assessed based on the risk ratio (RR). Ranking of the individual agents was performed with a frequentist approach (P-score and a multidimensional scaling [MDS] rank system) and a Bayesian ranking (surface under the cumulative ranking [SUCRA]). Regarding the overall data, SGLT-2is reduced the CV death risk by 12% (RR: 0.88, 95% CI 0.80-0.96). All three scoring methods resulted in empagliflozin scoring the highest. There was a 15% RR reduction in CV death (95% CI 0.71-1.02) in the ASCVD and multiple cardiovascular risk factor (MRF) groups and an 11% RR reduction in the HF group, with empagliflozin ranking the highest in the former group and dapagliflozin in the latter. Empagliflozin ranked the highest compared to the other SGLT-2is in the overall population and the trials including type 2 diabetes (T2D) patients with ASCVD or MRF at baseline, while dapagliflozin ranked the highest in the trials of patients with HF at baseline. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022381556, identifier CRD42022381556.

Evaluating the Safety of Sodium-Glucose Cotransporter-2 Inhibitors in a Nationwide Veterans Health Administration Observational Cohort Study

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are indicated in patients with or without type 2 diabetes mellitus atherosclerotic cardiovascular disease, chronic kidney disease, or heart failure. Postmarket surveillance data have identified many safety signals which warrants further investigation. We aimed to compare the safety of SGLT-2i and glucagon-like peptide-1 receptor agonists (GLP-1RA). Using the Veterans Health Administration nationwide database, patients with type 2 diabetes mellitus who were newly initiated on a SGLT-2i or GLP-1RA between April 1, 2013 and September 1, 2020 were identified. The primary outcome was the incidence of any amputation, below-knee amputation (BKA), all clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, diabetic ketoacidosis (DKA), serious urinary tract infections (UTIs), and venous thromboembolism (VTE). All outcomes were compared between the treatment groups. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) for the comparative analysis. A total of 70,694 propensity-matched new users of SGLT-2i and GLP-1RA were identified. The use of SGLT-2 inhibitors, compared with GLP-1RA, was not associated with an increased rate of any amputation (aHR 1.02, 95% confidence interval [CI] 0.82 to 1.27), BKA (aHR 1.05, 95% CI 0.84 to 1.32), all clinical fractures (aHR 0.94, 95% CI 0.86 to 1.03), hip fractures (aHR 0.82, 95% CI 0.50 to 1.32), DKA (aHR 1.66, 95% CI 0.97 to 2.85), VTE (aHR 1.02, 95% CI 0.80 to 1.30), acute pancreatitis (aHR 1.02, 95% CI 0.80 to 1.30), and Fournier gangrene (aHR 0.92 95% CI 0.61 to 1.38). Lower rates of serious UTIs were observed in the SGLT-2i group than in the GLP-1RA group (aHR 0.74, 95% CI 0.64 to 0.84). This real-world study found that SGLT-2i use compared with GLP-1RA did not increase the rate of amputation, BKA, clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, DKA, serious UTIs, and VTE in veteran patients.

SGLT2 inhibitors can reduce the incidence of abnormal blood glucose caused by statins in non-diabetes patients with HFrEF after PCI

BackgroundTaking statins for a long time is associated with an increased risk of new-onset diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can reduce insulin resistance and improve pancreatic β-cell function.Methods and resultsIn total, 333 non-diabetes patients with heart failure with reduced ejection fraction (HFrEF) after percutaneous coronary intervention (PCI) are included. The enrolled patients are divided into a matched group (n = 198) and an SGLT2 inhibitors group (n = 135). There are no statistical differences in general information between the two groups before treatment. After a mean follow-up time of 13 months, abnormal blood glucose levels are significantly higher in the matched group than in the SGLT2 inhibitors group (6.06 vs. 0.74%, P < 0.05). There are no statistically significant differences in the alanine aminotransferase (ALT), uric acid (UA), and estimated glomerular filtration (eGFR) levels between the two groups.ConclusionSGLT2 inhibitors play a significant protective role in reducing the risk of statins-induced abnormal blood glucose in non-diabetes patients with HFrEF after PCI, without increasing the burden on the heart, kidneys, and liver.

468-P: Use of New Glucose-Lowering Drugs and the Risk of Major Adverse Cardiovascular Events in People with Type 2 Diabetes and Prior Stroke

Background: It remains uncertain whether the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and incretin-based drugs is associated with a reduced risk of major adverse cardiovascular events (MACE) compared with that of thiazolidinediones (TZDs) in people with type 2 diabetes and stroke. Objectives: To compare the effectiveness of SGLT2is, incretin-based drugs, and TZDs on MACE in people with type 2 diabetes and prior stroke. Methods: We did a population-based cohort study involving 117,355 individuals who underwent health checkups under the Korean National Health Insurance Service from 2014 to June 2021 and followed up until December 2021. The primary outcome was MACE, defined as a composite of myocardial infarction, ischemic stroke, and all-cause death. We used propensity score weighting for balancing baseline covariates between treatment groups. Weighted cox proportional regression analyses were used to estimate the association of treatments with MACE after adjusting confounders. Results: In a new-user cohort, the incidence rate of MACE was 547, 679, and 625 per 1,000 person-years in the SGLT2i, incretin-based drug, and TZD groups, respectively. Compared with the TZD group, the risk of MACE was significantly reduced in the SGLT2i group (adjusted hazard ratio [HR] 0.87; 95% CI 0.79-0.96) but increased in the incretin-based drug group (adjusted HR 1.11; 95% CI 1.03-1.19). No significant differences were observed in the risk of myocardial infarction and ischemic stroke between the groups. The risk of all-cause death was significantly increased in the incretin-based drug group (adjusted HR 1.14; 95% CI 1.03-1.25) compared with the TZD group. Conclusion: In this population-based study of people with type 2 diabetes and stroke, SGLT2is were associated with a reduced risk of MACE compared with incretin-based drugs and TZDs. Incretin-based drugs were associated with an increased risk of MACE compared with TZDs. Disclosure J.Bae: None. J.Choi: None. N.Kim: None. S.Kim: None.

881-P: Heterogenous Effects of SGLT2 Inhibitors on Nephrolithiasis in Older Adults with Type 2 Diabetes

Mechanistic studies suggested that sodium-glucose cotransporter-2 inhibitors (SGLT2i) may reduce the risk of nephrolithiasis. We aimed to further assess this association using a real-world population of type 2 diabetes (T2D) patients. Among a 15% random sample of 2017-2018 Medicare fee-for-service beneficiaries with T2D, we identified new initiators of SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i). We followed the cohort until the first medical encounter with diagnosis of nephrolithiasis, death, or 12/31/2018. Inverse probability treatment weighting was used to balance the baseline covariates including sociodemographics, prior comorbidities and medications. Of 116,506 included individuals (age 72±10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days. The crude incidence rate was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i exposure was associated with a significantly lower risk of nephrolithiasis (hazard ratio 0.81 [95% CI 0.66-0.99]). This effect was more evident in men, non-Hispanic Black (NHB) individuals, and those without a history of nephrolithiasis. (Figure) SGLT2i was associated with a lower risk of nephrolithiasis, and the effect was more pronounced in men, NHB, and those without a history of nephrolithiasis. Disclosure Y.Li: None. H.Shao: Consultant; Lilly Diabetes. Y.Guo: None. Y.Zhang: None. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. L.Shi: None. J.Bian: None. A.G.Winterstein: Consultant; Bayer Inc., Genentech, Inc., Ipsen Biopharmaceuticals, Inc., Research Support; Merck Sharp &amp; Dohme Corp. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.

880-P: Effects of Sodium–Glucose Cotransporter-2 Inhibitors on the Risk of Atrial Fibrillation in Older Adults with Type 2 Diabetes

Clinical evidence suggested a protective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the risk of atrial fibrillation (AF) in type 2 diabetes (T2D) patients, but the results were mixed. We aimed to compare the risk of AF in SGLT2i users compared to dipeptidyl peptidase-4 inhibitors (DPP4i) users and determine the effect in different subgroups. Using a 15% random sample of 2017-2018 Medicare claims data, we identified individuals with T2D, no preexisting AF, and initiated SGLT2i or DPP4i. The index date was defined as the date of the first filled prescription of SGLT2i or DPP4i. The outcome was the first incident of diagnosed AF. Inverse probability treatment weighted Cox regression models were used for analyses. Of the 97,660 eligible individuals (age 71.2±9.8 years, 54.6% women), 1.01% (n=989) had incident AF over a median follow-up of 361 days. The crude incidence rate was 8.39 (95% CI: 6.67-9.99) and 11.70 (95% CI: 10.9-12.55) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i was associated with a significantly lower risk of incident AF (HR 0.72 [95% CI 0.56-0.89]) than DPP4i. The risk reduction of incident AF was more pronounced in Hispanic individuals and subgroups with existing cardiovascular (CV) and renal conditions. (Figure) Use of SGLT2i was associated with a lower risk of AF in individuals with T2D. Disclosure Y.Li: None. Y.Guo: None. S.Kimmel: Consultant; GlaxoSmithKline plc., Other Relationship; Janssen Research &amp; Development, LLC. J.Bian: None. D.Schatz: Advisory Panel; Medtronic, Avotres Inc., QuLab Medical Ltd., Kriya Therapeutics. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.