Impact Of Sodium-glucose Cotransporter 2 Inhibitors Research Articles

Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

Abstract 50: Sodium-Glucose Cotransporter 2 Inhibitors Use in Diabetic Patients With Acute Ischemic Stroke is Linked to Favorable Neurological Outcomes

Background: The benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in acute ischemic stroke (AIS) have been demonstrated preclinically. Here, we evaluated the neurological effects of SGLT2i use after stroke in patients with diabetes and AIS. Methods: Using a prospective stroke registry, we reviewed consecutive diabetic patients with AIS. Patients with and without SGLT2i use were 1:4 propensity score-matched for clinical variables. Clinical outcomes, including early neurological deterioration (END) during admission, National Institutes of Health Stroke Scale (NIHSS) score at discharge, and modified Rankin Scale (mRS) scores at discharge and at 3 months, were compared. The impact of SGLT2i on metabolic activity of various organs was examined in another cohort using 18 F-fluorodeoxyglucose positron emission tomography post-stroke. Results: Among the 820 eligible patients, 90 (11.0%) were prescribed SGLT2i on admission, and 76 continued the prescription at discharge. Seventy-four patients with and 266 patients without SGLT2i use were propensity score-matched and analyzed. SGLT2i did not increase the END risk (adjusted odds ratio [aOR] 0.48, 95% confidence interval [CI] 0.20-1.19). There was no significant difference in clinical outcomes at discharge between the two groups (NIHSS: B [standard error] -1.321 [0.952], p=0.17; mRS: aOR for favorable mRS 1.47, 95% CI 0.93-2.32). SGLT2i demonstrated significant improvement in the 3-month mRS (aOR 1.73, 95% CI 1.10-2.74). The positron emission tomography cohort showed that SGLT2i prescription was associated with elevated brown and subcutaneous adipose tissue metabolism. Conclusions: SGLT2i may be a priority for diabetic patients with AIS because of its potential benefits on long-term outcomes.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P=0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P=0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors in the Management of Chronic Kidney Disease: A Middle East and Africa Perspective.

Chronic kidney disease (CKD) is a major public health concern in the Middle East and Africa (MEA) region and a leading cause of death in patients with type 2 diabetes mellitus (T2DM) and hypertension. Early initiation of sodium-glucose cotransporter - 2 inhibitors (SGLT-2i) and proper sequencing with renin-angiotensin-aldosterone system inhibitors (RAASi) in these patients may result in better clinical outcomes due to their cardioprotective properties and complementary mechanisms of action. In this review, we present guideline-based consensus recommendations by experts from the MEA region, as practical algorithms for screening, early detection, nephrology referral, and treatment pathways for CKD management in patients with hypertension and diabetes mellitus. This study will help physicians take timely and appropriate actions to provide better care to patients with CKD or those at high risk of CKD.

Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials.

Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR-Preserved and EMPEROR-Reduced trials. Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy-terminal propeptide (PICP), a fragment of N-terminal type III collagen (PRO-C3), procollagen type I amino-terminal peptide (PINP), a fragment of C-terminal type VIa3 collagen (PRO-C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO-C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high-sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO-C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO-C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91-0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88-0.97, p = 0.003). Additionally, empagliflozin reduced PRO-C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95-1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89-0.98, p = 0.003), without impact on other collagen markers. Our observations are consistent with experimental observations that empagliflozin down-regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated.

Impact of SGLT2 inhibitors on patient outcomes: a network meta-analysis

BackgroundA comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted.MethodsWe searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin).ResultsA total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69–0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80–1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58–0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62–0.90).ConclusionsOur network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors.Trial registration: PROSPERO [CRD42022361906].

Sodium-glucose co-transporter-2 inhibitors and the risk of venous thromboembolism: A nationwide population-based study and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p<0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p=0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p<0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p=0.43), suggesting the robustness of our retrospective analysis. In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.

The Effects of Sodium-Glucose Cotransporter2 Inhibitors on Body Composition in Type2 Diabetes Mellitus: A Narrative Review.

Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM.

Association between Obstructive Sleep Apnea and Heart Failure in Adults-A Systematic Review.

Heart failure (HF) patients commonly experience obstructive sleep apnea (OSA), which may worsen their condition. We reviewed a diverse range of studies to investigate the prevalence of OSA in HF patients, the effects of positive airway pressure (PAP) treatment, and the potential impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and sacubitril/valsartan on OSA outcomes. We analyzed case-control, observational studies, and randomized controlled trials. Prevalence rates, PAP treatment, and HF pharmacotherapy were assessed. Numerous studies revealed a high prevalence of OSA in HF patients, particularly with preserved ejection fraction. PAP treatment consistently improved an apnea-hypopnea index, left ventricular ejection fraction, oxygen saturation, and overall quality of life. Emerging evidence suggests that SGLT2i and sacubitril/valsartan might influence OSA outcomes through weight loss, improved metabolic profiles, and potential direct effects on upper airway muscles. The complex interplay between OSA and HF necessitates a multifaceted approach. PAP treatment has shown promising results in improving OSA symptoms and HF parameters. Additionally, recent investigations into the effects of HF pharmacotherapy on OSA suggest their potential as adjunctive therapy. This review provides insights for clinicians and researchers, highlighting the importance of addressing OSA and HF in patient management strategies.

The Impact of SGLT2 Inhibitors on Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

To evaluate the role of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with preserved ejection fraction (HFpEF). A literature search of PubMed, the Cochrane Library, and Google Scholar databases (January 2015 to June 20, 2023) was performed with keywords: sodium-glucose co-transporter 2 inhibitors OR SGLT2 inhibitors OR bexagliflozin OR canagliflozin OR dapagliflozin OR empagliflozin OR ertugliflozin OR sotagliflozin AND heart failure OR heart failure with preserved ejection fraction, and terms related to CV outcomes including cardiovascular death, hospitalization, hospitalization for heart failure, mortality, death, and major adverse cardiovascular event (MACE). The reference list from retrieved articles as well as relevant review articles was considered. Pivotal randomized controlled trials and meta-analyses with a primary or secondary end point of CV death or heart failure hospitalization were included. Studies conducted solely in a diabetic patient population were excluded. Dapagliflozin and empagliflozin, in a broad population of heart failure patients including, HFrEF, HFmrEF, HFpEF, and without diabetes, have shown consistent improvement in the combined outcome of CV death and hospitalization for heart failure (HR 0.80, 95% CI 0.73-0.87) and in the reduction of heart failure hospitalizations (HR 0.74, 95% CI 0.67-0.83). In patients with HFpEF, cardiovascular mortality was not demonstrated (HR 0.88, 95% CI 0.77-1.00). Rates of adverse events were low. Patients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure derive the most benefit from SGLT2 inhibitors with an overall goal of a reduction in heart failure hospitalizations. The treatment of HFpEF has made progress, but there is still work to be done. Now, SGLT2 inhibitor therapy can be used to further help with symptom control and reduce overall hospitalizations for heart failure.

The impact of sodium-glucose cotransporter-2 inhibitors on the outcome of patients with colorectal adenocarcinoma.

3583 Background: The mortality of colorectal cancer remains high despite the development of novel anti-neoplastic agents. Preclinical studies have shown that colorectal cancer upregulates the expression of sodium-glucose cotransporter 2 (SGLT2) channels and inhibition of these channels by SGLT2 inhibitors (SGLT2i) reduces tumor proliferation. We aimed to investigate the impact of SGLT2i on the outcome of patients with colorectal cancer. Methods: We conducted a retrospective cohort study by including all adult patients with colorectal adenocarcinoma and type 2 diabetes mellitus in two tertiary centers in Taiwan. SGLT2i and non-SGLT2i patients were matched 1:1 based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with the use of SGLT2i. Results: We identified 1347 patients with colorectal cancer and type 2 diabetes mellitus, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of OS (5-year OS: 86.2% [95% CI: 72.0-93.5] vs. 62.3% [95% CI: 50.9-71.8], p = 0.013) and PFS (5-year PFS: 76.6% [95% CI: 60.7-86.7] vs. 57.0% [95% CI: 46.2-66.4], p = 0.021). In Cox proportional hazard analyses, the use of SGLT2i was associated with a 50-70% reduction in the risk of all-cause mortality and disease progression. The rate of cancer-associated mortality was lower in the SGLT2i group (7% vs. 21%, p = 0.005). SGLT2i were not associated with an increased risk of sepsis, hypoglycemia, or acute kidney injury. We did not detect any cases of urosepsis or diabetic ketoacidosis in the SGLT2i group. Conclusions: The use of SGLT2i was associated with a higher rate of survival in colorectal cancer patients with diabetes mellitus. [Table: see text]

Empagliflozin reduces arrhythmogenic effects in rat neonatal and human iPSC-derived cardiomyocytes and improves cytosolic calcium handling at least partially independent of NHE1

The antidiabetic agent class of sodium-glucose cotransporter 2 (SGLT2) inhibitors confer unprecedented cardiovascular benefits beyond glycemic control, including reducing the risk of fatal ventricular arrhythmias. However, the impact of SGLT2 inhibitors on the electrophysiological properties of cardiomyocytes exposed to stimuli other than hyperglycemia remains elusive. This investigation tested the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) affects cardiomyocyte electrical activity under hypoxic conditions. Rat neonatal and human induced pluripotent stem cell (iPSC)-derived cardiomyocytes incubated or not with the hypoxia-mimetic agent CoCl2 were treated with EMPA (1 μM) or vehicle for 24 h. Action potential records obtained using intracellular microelectrodes demonstrated that EMPA reduced the action potential duration at 30%, 50%, and 90% repolarization and arrhythmogenic events in rat and human cardiomyocytes under normoxia and hypoxia. Analysis of Ca2+ transients using Fura-2-AM and contractility kinetics showed that EMPA increased Ca2+ transient amplitude and decreased the half-time to recover Ca2+ transients and relaxation time in rat neonatal cardiomyocytes. We also observed that the combination of EMPA with the Na+/H+ exchanger isoform 1 (NHE1) inhibitor cariporide (10 µM) exerted a more pronounced effect on Ca2+ transients and contractility than either EMPA or cariporide alone. Besides, EMPA, but not cariporide, increased phospholamban phosphorylation at serine 16. Collectively, our data reveal that EMPA reduces arrhythmogenic events, decreases the action potential duration in rat neonatal and human cardiomyocytes under normoxic or hypoxic conditions, and improves cytosolic calcium handling at least partially independent of NHE1. Moreover, we provided further evidence that SGLT2 inhibitor-mediated cardioprotection may be partly attributed to its cardiomyocyte electrophysiological effects.

Potential favorable action of sodium-glucose cotransporter-2 inhibitors on sudden cardiac death: a brief overview.

The primary pharmacological action of sodium-glucose co-transporter 2 (SGLT2) inhibitors is to inhibit the reabsorption of glucose and sodium ions from the proximal tubules of the kidney and to promote urinary glucose excretion. Notably, several clinical trials have recently demonstrated potent protective effects of SGLT2 inhibitors in patients with heart failure (HF) or chronic kidney disease (CKD), regardless of the presence or absence of diabetes. However, the impact of SGLT2 inhibitors on sudden cardiac death (SCD) or fatal ventricular arrhythmias (VAs), the pathophysiology of which is partly similar to that of HF and CKD, remains undetermined. The cardiorenal protective effects of SGLT2 inhibitors have been reported to include hemodynamic improvement, reverse remodeling of the failing heart, amelioration of sympathetic hyperactivity, correction of anemia and impaired iron metabolism, antioxidative effects, correction of serum electrolyte abnormalities, and antifibrotic effects, which may lead to prevent SCD and/or VAs. Recently, as possible direct cardiac effects of SGLT2 inhibitors, not only inhibition of Na+/H+ exchanger (NHE) activity, but also suppression of late Na+ current have been focused on. In addition to the indirect cardioprotective mechanisms of SGLT2 inhibitors, suppression of aberrantly increased late Na+ current may contribute to preventing SCD and/or VAs via restoration of the prolonged repolarization phase in the failing heart. This review summarizes the results of previous clinical trials of SGLT2 inhibitors for prevention of SCD, their impact on the indices of electrocardiogram, and the possible molecular mechanisms of their anti-arrhythmic effects.

Potential Global Impact of Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are effective across the spectrum of the left ventricular ejection fraction (LVEF) in heart failure (HF); however, population-wide medication use in eligible patients remains suboptimal. We evaluated the potential implications of optimal global implementation of SGLT-2 inhibitors in HF. A decision analytical study was performed using the global prevalence of HF from the Global Burden of Disease 2017 report. Exclusion criteria were applied using the NHANES to ascertain an SGLT-2 inhibitor-eligible population, which was mapped onto global LVEF distributions from the REPORT-HF registry. The number needed to treat for 3 years for the composite of worsening HF events and cardiovascular deaths was calculated from estimated event rates in the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, and DELIVER trials and projected onto the eligible population. An estimated 49,329,000 (95%CI, 43,882,000-54,929,000) HF patients would be eligible for SGLT-2 inhibitors across all LVEFs, including 25,651,000 (95%CI, 22,818,000-28,563,000) with LVEF of <40% and 23,678,000 (95%CI, 21,063,000-26,366,000) with LVEF >40%. Optimal implementation of SGLT-2 inhibitors would be projected to prevent/postpone 4,512,011 (95%CI, 4,013,686-5,024,232) to 5,986,943 (95%CI, 5,325,721-6,666,604) total worsening HF events and cardiovascular deaths over 3 years in patients with LVEF <40%. An additional 2,102,606 (95%CI, 1,870,394-2,341,301) to 2,557,224 (95%CI, 2,274,804-2,847,528) events would be prevented/postponed in patients with LVEF >40%. Among all eligible HF patients, irrespective of LVEF, 7,069,235 (95%CI, 6,288,490-7,871,760) to 8,089,549 (95%CI, 7,196,115-9,007,905) total worsening HF events and cardiovascular deaths would be prevented/postponed over this period. Optimal implementation of SGLT-2 inhibitors globally in HF is projected to prevent approximately 7-8 million worsening HF events and cardiovascular deaths over 3 years. This article is protected by copyright. All rights reserved.

Association between SGLT2 (sodium-glucose cotransporter-2) inhibitors and bladder cancer in individuals with type 2 diabetes; a systematic review and meta-analysis

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are the most recent pharmaceutical group for type 2 diabetes (T2D) treatment. Evidence indicates contradictory relationships between sodium-glucose cotransporter-2 inhibitors and bladder cancer (BC). Hence, this study aims to investigate the relationship between SGLT2 inhibitors and BC in patients with T2D. Materials and Methods: This study is a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). International databases including Cochrane, Web of Science, Scopus, PubMed, and Google Scholar were conducted for searching with keywords and without time and language limitations. The reference searching stage continued upgrading until November, 2022. Data analysis was performed with STATA 14 software. The tests with P values lower than 0.05 were considered statistically significant. Results: The four reviewed studies with a sample size comprising 497 755 individuals indicated the impact of SGLT2 inhibitors on BC of patients with T2D (OR: 0.68; 95% CI: 0.37, 1.2). The effect of dapagliflozin, canagliflozin and empagliflozin administration on the incidence of BC among the T2D patients were (OR: 0.72; 95% CI: 0.39, 1.30), (OR: 0.53; 95% CI: 0.23, 1.20), and (OR: 0.51; 95% CI: 0.20, 1.28), respectively. Conclusion: The general conclusion of this study revealed that SGLT2 inhibitors did not increase the risk of BC in T2D patients. The analysis of subgroups also indicated that the administration of dapagliflozin, canagliflozin, and empagliflozin also did not increase the risk of BC in T2D patients. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID=CRD42023389014).

Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Urolithiasis

Urolithiasis is a common disease with an estimated global prevalence of up to 15% and a recurrence rate of up to 50%. Diabetes mellitus has been implicated as a risk factor for urolithiasis.1 The mechanism underlying the increased risk of urolithiasis in patients with diabetes mellitus may involve high uric acid excretion, impaired ammoniagenesis, and a subsequent decrease in urinary pH levels resulting from insulin resistance. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have diuretic and anti-inflammatory effects.

Impact of sodium-glucose cotransporter-2 inhibitors on kidney outcomes in type 2 diabetes: A tertiary center experience.

Diabetic nephropathy (DN) is a complication of chronic hyperglycemia associated with diabetes mellitus (DM). Several studies have demonstrated the positive impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on kidney outcomes. The objective of the study was to evaluate the effects of dapagliflozin, an SGLT2 inhibitor, on kidney outcomes in Saudi patients with type 2 DM. Study included all Saudi patients with type 2 DM who visited our center from August 1, 2021, to July 31, 2022, and had been on dapagliflozin for at least 3 months. Data was abstracted through chart review for all patients included in the study. Paired t-test or Wilcoxon signed-rank test were used to compare the results before and after treatment for continuous variables and the McNemar test was used to compare the results for categorical data. Study included 184 Saudi patients with type 2 diabetes with a mean age of 61.32 years (SD=9.37). Dapagliflozin 10 mg/day significantly reduced hemoglobin A1C (HbA1C) from a mean (SD) of 9.00 to 8.40 (P < 0.001). Among a subgroup of patients with significant proteinuria (n = 83), dapagliflozin significantly reduced ACR from a median of 93.1 to 64.9 mg/g (P = 0.001). Following treatment, the estimated glomerular filtration rate improved from a mean of 69.83 to 71.68 mL/min and the mean arterial pressure (MAP) fell from 90.03 to 89.06 mmHg, both were not statistically significant. Despite a statistically insignificant increase in the episodes of urinary tract infections (UTIs), the hospitalization rate declined. No episodes of amputations or ketoacidosis occurred during the study period. SGLT2 inhibitors had beneficial effects among Saudi patients with type 2 diabetes by improving diabetic control and lowering proteinuria. Dapagliflozin did not result in significant harm, including UTIs, amputations, and ketoacidosis.

Impact of SGLT2 inhibitors on the evolution of echocardiographic parameters of patients with chronic heart failure

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) have shown, in several prospective studies, their cardiovascular benefit with more particularly a rapid and very significant decrease in hospitalizations for heart failure. The precise mechanisms accounting for the improvement of myocardial function under SGLT2 inhibitors are not yet clarified. The objective of this work is to evaluate the effect of the introduction of SGLT2, in patients with heart failure under optimal treatment, on echocardiographic parameters of left ventricular function. Descriptive analytical study conducted in 40 patients with chronic heart failure with reduced LVEF already receiving optimal treatment, based on angiotensine converting enzyme (ACE), beta-blockers and anti-aldosterone, in which we introduced dapagliflozin at 5–10 mg/day. An echocardiographic evaluation of systolodiastolic left ventricular function and longitudinal function by calculating the GLS was performed before and 3 months after initiation of treatment. Of the 40 patients, 28 of them had type 2 diabetes. On average, 82% of patients had high left ventricular systolic pressure, The mean left ventricular ejection fraction was 40 ± 3.6 before and 41.5 ± 2.5 after treatment, (P = 0.2). Analysis of diastolic function shows an E/E’ ratio at 14.2 ± 3.0 before and 08.1 ± 2.5 after treatment, (P = 0.0001), The index at 0.54 ± 0.03 before and 0.47 ± 0.02 after treatment (P = 0.004), systolic pulmonary blood pressures were 45 ± 5 mmHg before and 34 ± 3 after treatment (P < 0.000), the average GLS was −11.5 ± 2.6 before and −14.5 ± 2.7 after treatment (P < 0.000). SGLT2 inhibitors are agents with pleiotropic effects that, in addition to reducing blood sugar, provide cardiovascular benefits, by lowering preload and postloading. Cardiac fibrosis is recognized as an important pathophysiological factor in the development of heart failure. Several studies indicate an antifibrotic effect of SGLT2 inhibitors. Our modest work confirmed the positive impact of SGLT2 on the improvement of left ventricular function parameters and therefore prognosis.

Impact of SGLT2 Inhibitor Therapy on Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction

Background: The impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on the right ventricular (RV) systolic function using advanced echocardiographic analysis among outpatients with heart failure and a reduced ejection fraction (HFrEF) has thus far been poorly investigated. Methods: This was a single-center, prospective, single-blinded study in which an echocardiographic expert was blinded to the allocation of the treatment. A total of 36 outpatients with HFrEF were randomized to either OMT or OMT+SGLT2i. Both groups underwent an echocardiographic examination of the RV systolic function at the baseline and at the 3-month follow-up (3mFU). Results: The patients in both groups did not significantly differ with respect to the relevant baseline comorbidities, therapy, and clinical characteristics. The patients receiving OMT+SGLT2i showed a significant improvement from the baseline to the 3mFU in all the measured RV echocardiographic parameters, while for the OMT group, a significant improvement after the 3mFU was observed for TAPSE and s'. The mean percent change from the baseline to the 3mFU was significant when comparing OMT+SGLT2i to the OMT group concerning RV FWS (+91% vs. +28%, p = 0.039), TR maxPG (-27% vs. +19%, p = 0.005), and TR Vmax (-17% vs. +13%, p = 0.008), respectively. Conclusions: Adding SGLT2i to OMT in patients with HFrEF resulted in a greater improvement in the RV systolic function from the baseline to the 3mFU compared to the OMT alone.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer

ObjectivesSodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer...