Effects Of Sodium-glucose Cotransporter Research Articles

The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis

ObjectivesTo provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). MethodsPubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs). ResultsA total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97). ConclusionIn this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

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

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

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0±11.5years (mean±standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8±9.9% and QRS duration of 161±29ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n=66) and without (n=308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P=0.049). We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cause-Specific Cardiovascular Death in Patients with CKD: A Meta-Analysis of CKD Progression Trials.

Clinical Trial registry name and registration number: ClinicalTrials.gov Identifiers: NCT02065791 (CREDENCE), NCT03036150 (DAPA-CKD), NCT03594110 (EMPA-KIDNEY).

Effects of Sodium-Glucose Co-transporter 2 Inhibitors on Cognition in Patients with Diabetes: A Systematic Review and Meta-analysis (P11-9.002)

Effects of Sodium-Glucose Co-transporter 2 Inhibitors on Cognition in Patients with Diabetes: A Systematic Review and Meta-analysis (P11-9.002)

Effect of sodium glucose cotransporter 2 inhibition immediately prior to heart transplantation

Effect of sodium glucose cotransporter 2 inhibition immediately prior to heart transplantation

Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.

The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

Effect of sodium-glucose cotransporter 2 inhibitor canagliflozin on interstitial glucose concentration in insulin-treated diabetic dogs.

The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs. Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs. Five insulin-treated diabetic dogs. Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL. Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001). Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.

Analysis methods and case analysis of effect modification (3): effect modification in individual patient data Meta-analysis

This paper briefly introduces the unique advantages, overall analysis ideas and existing analysis methods of individual patient data Meta-analysis in terms of effect modification. In addition to Meta-regression and subgroup analysis, this paper also introduces the analysis methods based on part of individual patient data integrated with aggregated data and summarizes the current reporting of the above mentioned methods. In addition, the application and results interpretation of the above mentioned methods in individual patient data Meta-analysis are presented in this paper by taking "Effects of sodium-glucose cotransporter 2 inhibitors on SBP in patients with type 2 diabetes" as an example and by introducing their advantages and limitations.

Effect of sodium-glucose cotransporter 2 inhibitors on serum low-density lipoprotein cholesterol in Japanese patients with type 2 diabetes mellitus.

We aimed to evaluate factors that influence changes in blood low-density lipoprotein cholesterol (LDL-C) levels after treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors in Japanese patients with type 2 diabetes. We retrospectively analyzed clinical data of outpatients newly initiated on SGLT2 inhibitors (n = 176) and other oral antidiabetic drugs (n = 227). The patients were classified into four subgroups according to statin administration and baseline LDL-C levels (<120 or ≥120 mg/dL). Clinical characteristics were compared among the subgroups. Multivariate analysis was carried out to identify factors contributing to changes in LDL-C. The median follow-up period was 13.0 weeks (range 11.9-14.1 weeks, min 8 weeks, maximum 16 weeks) in the SGLT2i group, and 12.0 weeks (range 10.0-14.0 weeks, min 8 weeks, maximum 16 weeks) in the control group. Both groups showed a significant decrease in LDL-C (SGLT2i group -3.8 ± 24.7 mg/dL, control group -3.4 ± 15.0 mg/dL). Multivariate regression analyses showed that in both groups, the change in LDL-C depended on statin use and baseline LDL-C levels. Stratified analyses showed that LDL-C level was significantly decreased in statin users with baseline LDL-C ≥120 mg/dL (from 148.9 ± 33.5 to 109.3 ± 17.9 mg/dL, P = 0.002), and significantly increased in statin non-users with baseline LDL-C <120 mg/dL (from 96.3 ± 27.3 to 104.7 ± 24.8 mg/dL, P = 0.002). These changes were more characteristic for SGLT2 inhibitors than for other oral antidiabetic drugs (P for interaction = 0.010 and <0.001, respectively). LDL-C levels and statin medication at baseline influence changes in LDL-C after SGLT2 inhibitors treatment in Japanese patients with type 2 diabetes.

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10mg once daily and then placebo or vice versa. Each treatment period will last 8weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

The effect of sodium-glucose cotransporter 2 inhibitors on left cardiac remodelling in heart failure with reduced ejection fraction: Systematic review and meta-analysis.

The therapeutic mechanism of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on left cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF) is not well-established. This study meta-analysed the impact of SGLT2i on left cardiac structure and function in patients with HFrEF. Online databases were queried up to April 2023 for trials reporting indicators of left cardiac structure and function in patients with HFrEF treated with SGLT2i. Data from studies were pooled using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). Six trials were included (n = 555). Compared with control, SGLT2i significantly improved left ventricular end-diastolic volume (LVEDV; WMD: -17.07 ml [-23.84, -10.31]; p < 0.001), LVEDV index (WMD: -5.62 ml/m2 [-10.28, -0.97]; p = 0.02), left ventricular end-systolic volume (LVESV; WMD: -15.63 ml [-26.15, -5.12]; p = 0.004), LVESV index (WMD: -6.90 ml/m2 [-10.68, -3.11]; p = 0.001), left ventricular ejection fraction (WMD: 2.71% [0.70, 4.72]; p = 0.008), and left atrial volume index (WMD: -2.19 ml/m2 [-4.26, -0.11]; p = 0.04) in patients with HFrEF. SGLT2i use was associated with a non-significant trend towards a reduction in left ventricular mass index (WMD: -6.25 g/m2 [-12.79, 0.28]; p = 0.06). No significant impact on left ventricular global longitudinal strain was noted (WMD: 0.21% [-0.25, 0.67]; p = 0.38). Sodium-glucose cotransporter 2 inhibitors improve cardiac structure and function in patients with HFrEF.

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n=89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR<60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR≥60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis=0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup<60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

Safety and Effectiveness of Sodium-Glucose Co-transporter 2 Inhibitors on Glycemic Control in Patients with Type 2 Diabetes Mellitus Fasting during Ramadan: A Review.

This review evaluates the current evidence on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. All studies included in the review were conducted in Asia and the Middle East. Overall, the evidence suggests that SGLT2 inhibitors are a safe and effective treatment option for most T2DM patients fasting during Ramadan. The average incidence of symptomatic hypoglycemia is 12.5%, but ranges from 0.7% to 27%, depending on the study population and concomitant use of other medications. The risk of hypoglycemia is increased when SGLT2 inhibitors are used in combination with insulin and/or sulfonylureas. Therefore, patients taking SGLT2 inhibitors in combination with insulin and/or sulfonylureas can take steps to mitigate this risk, such as having their insulin and/or sulfonylurea doses adjusted and being closely monitored for hypoglycemia. Patients taking SGLT2 inhibitors may be at increased risk of dehydration. To mitigate the risk of dehydration, patients should be advised to consume adequate fluids during the fast-breaking hours. Further research is warranted to validate these findings and extend their applicability to high-risk populations and other regions of the world.

The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: A systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM). However, their efficacy in patients with chronic kidney disease (CKD) with or without T2DM has not yet been analyzed. To assess the cardiovascular and renal effects of SGLT-2 inhibitors in patients with CKD with and without T2DM, including all CKD patients in the current literature. We searched MEDLINE, EMBASE, CENTRAL and Scopus for randomized controlled trials of SGLT-2 inhibitors that evaluated cardiovascular and kidney outcomes in patients with CKD, or trials in which these patients were a subgroup. We defined 2 primary outcomes: a composite of cardiovascular death or hospitalization for heart failure, and a composite renal outcome. For each outcome, we obtained overall hazard ratios with 95% confidence intervals by using a random effects model. We included 14 randomized controlled trials. SGLT-2 inhibitors decreased the hazard for the primary cardiovascular outcome (HR 0.76; [95% CI 0.72-0.79]) and the primary renal outcome (HR 0.69; [95% CI 0.61-0.79]) in patients with CKD with or without T2DM. We did not find significant differences in the subgroup analyses according to diabetes status, baseline eGFR values or the type of SGLT-2 inhibitor used. In patients with CKD, treatment with SGLT-2 inhibitors in addition to standard therapy conferred protection against cardiovascular and renal outcomes. Further research on patients with non-diabetic CKD should be done to confirm the utility of these medications in this population. (PROSPERO ID: CRD42021275012).

Short term effect of sodium glucose cotransporter 2 inhibitors and sacubitril/valsartan on comprehensive geriatric assessment and oxidative stress in elderly with chronic heart failure (from MAGIC-HF)

Abstract Background Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) and Sacubitril/Valsartan (Sac/Val) have improved clinical prognosis in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF). Cognitive impairment, depression, and poor physical functional performance are a very common comorbidity in patients with HF and result in a worse prognosis. Purpose The aim of this study was to evaluate the potential effects of SGLT2i on functional, humoral, and cognitive aspects, assessed by performing a comprehensive geriatric assessment (CGA), and on oxidative stress and platelets activation biomarkers, in a cohort of HFrEF elderly, and any differences between men and women. Methods We enrolled 91 HFrEF patients (63 men and 28 women, mean age 73.7±4.7 years) in the "MAgna GraecIa evaluation of Comorbidities in patients with Heart Failure STUDY (MAGIC-HF STUDY). Men and women differed for use of glucagon-like-peptide 1 receptor agonists, antiplatelet drugs, and circulating levels of NADPH Oxidase 2 (Nox-2). SGLT2i therapy was introduced in patients already treated with Sac/Val for at least 12 months who were taking an average dose of 273.6±102.0 mg/die. Results After 3 months follow-up, we observed a significant improvement in cognitive, humoral and functional parameters of CGA, NTpro-BNP levels and echocardiographic parameters. Changes (Δ) in Montreal Cognitive Assessment (MoCA) (p=0.015) and Cardiac Index (CI) which were greater in men (p&amp;lt;0.0001) and Geriatric Depression Scale (GDS) which were greater in women (p=0.029). In the whole population, multivariate analysis shows that Δ of CI, Homeostatic model assessment (HOMA), Sp-Selectina, Nox-2 and 8-Isoprostane contributed for 19.7% (p&amp;lt;0.0001), 9.4% (p=0.001), 6.4% (p=0.002), 3.8% (p=0.013) and 2.9% (p=0.024) to Mini mental state examination (MMSE) variability, respectively, and the whole model accounted for a 42.2% of MMSE variation; moreover Δ of HOMA, Sp-Selectina and highly sensitive c-reactive protein (hs-CRP) contributed for 21.6% (p&amp;lt;0.0001), 5.7% (p=0.002) and 4.0% (p=0.014) to MoCA variability, respectively, and the whole model accounted for a 33.3% of MoCA variation. In addition, Δ of Sp-Selectina, Nox-2, CI and HOMA globally contributed for 37.5% of GDS variation (p&amp;lt;0.05); and Δ of HOMA and Sp-Selectina contributed for 30.9% of Short performance physical battery variation (p&amp;lt;0.0001). Conclusions This represents the first real-world study carried out in an elderly population suffering from chronic HFrEF with several comorbidities, in which the addition of SGLT2i, in patients already treated with the best medical therapy including Sac/Val, after three months induced important improvements in clinical, humoral, hemodynamic, functional outcomes and cognitive performance. This study shows that echocardiographic and cognitive improvements are greater in men than in women, instead metabolic and humoral improvements are greater in women.

Lower risks of new-onset hip fracture risks in users of sodium glucose cotransporter 2 (SGLT2) inhibitors versus users of dipeptidyl peptidase-4 (DPP4) inhibitors: a propensity score-matched analysis

Abstract Purpose This study aimed to compare the effects of sodium glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset hip fractures. Methods This was a retrospective population-based cohort study including type-2 diabetes mellitus patients treated with either SGLT2I or DPP4I between January 1st 2015 and December 31st 2020 in Hong Kong. The primary outcome was new-onset hip fracture and the secondary outcome was all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regression were applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed. Results This cohort included 56393 patients with type-2 diabetes mellitus (median age: 62.1 years old [interquantile range, IQR]: 54.2-71.1; 57.45% males), of which 20432 patients ([incidence rate, IR]: 36.23%) used SGLT2I and 35961 patients (IR: 63.77%) used DPP4I. After the 1:1 propensity score matching, 449 (IR: 1.09%) patients had hip fractures, and 2012 patients (IR: 4.92%) died. SGLT2I was associated with significantly lower risks of hip fractures after adjusting for the demographics, past comorbidities, non-SGLT2I/DPP4I medications and laboratory results (hazard ratio: 0.55; 95% confidence interval: 0.42-0.89; P=0.0036). The results were consistent in the competing risk models and the different propensity matching approaches. Conclusions SGLT2I was associated with lower risks of new-onset hip fractures after propensity score matching and adjustments.Figure 1

Abstract 16478: Effect of Sodium Glucose Cotransporter 2 Inhibitors on Major Adverse Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

Introduction: The cardiac adverse events (irAEs) secondary to immune checkpoint inhibitors (ICI) are associated with a high rate of morbidity and mortality. There are no data on the effect of concomitant sodium glucose cotransporter 2 inhibitors (SGLT2i) on the rates of major adverse cardiovascular events (MACE) among patients treated with an ICI. Hypothesis: Whether, the use of SGLT2i among ICI-treated patients may reduce MACE. Methods: This was a population-based cohort study between 2014 and 2023 including cancer patients treated with ICI aged over 18 years across the United States. SGLT2i use while on an ICI was defined as the initiation of SGLT2i therapy after the first record of ICI treatment among patients currently undergoing ICI therapy. The risk of incident MACE in patients on an ICI who were also prescribed an SGLT2i therapy was compared with 1:1 propensity score-matched patients on ICI who were never prescribed an SGLT2i. Hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE were estimated using Cox proportional hazards regression. MACE was defined as a composite of myocardial infarction, heart failure (HF), and ischemic stroke. Results: There were 216 cancer patients undergoing ICI therapy who were newly treated with SGLT2i. These were compared to 216 controls. Over a mean follow-up period of six years, there were 107 MACE events. There were 44 events (20.4%) among those on an SGLT2i and 63 among controls (HR=0.61, 95% CI: 0.41-0.90; log-rank test p=0.011). Of the individual components of MACE, rates of HF were lower where there were 22 HF events (20.4%) among those on an SGLT2i and 37 among controls (HR=0.51, 95% CI: 0.30-0.86; log-rank test p=0.010). There were no differences in the rates of stroke (HR: 0.55, 95% CI: 0.29-1.04) and myocardial infarction (HR: 0.97, 95% CI: 0.38-2.43). Conclusions: In an observational, retrospective study, SGLT2i therapy was associated with a reduced risk for cardiac events compared to those who never treated with SGLT2i. These findings underscore the potential therapeutic value of SGLT2i in the prevention of MACE in cancer patients receiving immunotherapy and warrant further research.

Evaluation of the clinical value of sodium examination in spot urine in patients presenting with acute heart failure while using SGLT2i – ‘‘SPOT HF STUDY’’

Objectives: Sodium measurement in spot urine provides important information about the adequacy of the initial dose in acute heart failure (AHF) patients using intravenous diuretic (IV) and makes a guiding contribution to the titration decision. It is not clear whether spot urine sodium measurement has the same clinical value as the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) drugs on urinary electrolytes. Our aim in our study is to investigate the clinical value of sodium examination in spot urine in AHF patients while using SGLT2i. Methods: Our study was conducted retrospectively and single-centered. AHF patients, administered IV diuretics were included in the study. Patients who were using and were not using SGLT2i were examined in two groups. The 2nd and 6th-hour sodium values in spot urine were measured. Results: Patients using SGLT2i (n = 46) and not using it (n = 54) were included. The mean age was 69.91 ± 11.84 years and 47% were female. The standard deviation value for the sodium in spot urine in patients using SGLT2i was clearly high and its distribution was significantly higher. A weak correlation was found between the sodium value in spot urine and the 24-hour urine volume in this group. Hospitalization history within 1 month after discharge was found to be 39% in the group using SGLT2i, and 51% in the group that did not use it, and this difference was statistically significant. Conclusions: The measurement of sodium in spot urine does not seem to have the same clinical value in HF patients using SGLT2i. Its correlation with urine volume is also decreasing in this group.

The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Hemoglobin Levels in Patients with CKD

The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Hemoglobin Levels in Patients with CKD