Novel therapies for heart failure with reduced ejection fraction (HFrEF) are angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose co-transporter 2 inhibitor (SGLT2i), etc. The purpose of this review is to determine the effects of ARNI and SGLT2i in heart failure (HF), compare the impact of SGLT2i with ARNI, and finally evaluate the current data regarding the combination of these two drugs in HF. Various trials on the respective medications have shown some significant reduction in all-cause mortality and cardiovascular (CV) death. The combination of these drugs has shown more CV benefits than monotherapy. There is emerging data about these two drugs in patients with heart failure with preserved ejection fraction (HFpEF). At present, there are less head-to-head comparison trials of these two drugs. This review provides insights on the current evidence, comparative efficacy, and combination therapy of ARNI and SGLT2i in managing HF, focussing on HFrEF and HFpEF.

Chronic kidney disease (CKD) is a noncommunicable condition that has become a major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause that leads to the development of renal impairment is diabetes mellitus and, in contrast to other chronic complications such as retinopathy or neuropathy, it has been suggested that intensive glycemic control is not sufficient in preventing the development of diabetic kidney disease. Nevertheless, a novel class of antidiabetic agents, the sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shown multiple renoprotective properties that range from metabolic and hemodynamic to direct renal effects, with a major impact on reducing the risk of occurrence and progression of CKD. Thus, this review aims to summarize current knowledge regarding the renoprotective mechanisms of SGLT2i and to offer a new perspective on this innovative class of antihyperglycemic drugs with proven pleiotropic beneficial effects that, after decades of no significant progress in the prevention and in delaying the decline of renal function, start a new era in the management of patients with CKD.

OBJECTIVE: Contrast agents directly cause kidney toxicity in patients undergoing Percutaneous Intervention for cardiovascular disease with Type 2 diabetes. This meta-analysis aims to evaluate the effects of SGLT2-i on renal function in individuals undergoing Percutaneous Intervention.
METHODS: The databases used for the search included PubMed, Scopus, Cochrane Central Registry of Controlled Trials, and Google Scholar. We considered Randomized controlled trials and observational studies published from January 2013 to August 2023. The eligibility to include the studies was assessed independently. The Cochrane modified data extraction form, and Joanna Briggs Institute was used. The Cochrane risk of bias tool and Newcastle-Ottawa quality assessment scale were used to assess the quality of the studies. The certainty of the evidence was assessed using GradePro software.
RESULTS: The pooled estimate showed a substantial reduction in serum creatinine levels at 48- and 72-hours post-PCI who received SGLT2i (MD -9.57; 95% CI -18.36, -0.78; p-value 0.03) and (MD -14.40; 95% CI -28.57, -0.22; p-value 0.05). There was a decrease in the incidence of the CI-AKI among SGT2i users (RR: 0.46; 95% CI: 0.32, 0.67; p value< 0.0001). There was no significant difference in the number of patients requiring hemodialysis, but a smaller number of patients required hemodialysis among the SGLT2i users (RR: 0.88; 95% CI: 0.19, 4.07; p-value = 0.87).
CONCLUSIONS: The use of SGLT2i confers substantial beneficial effects on kidney function and reduction of incidence of Contrast-induced acute kidney injury among patients undergoing PCI procedures for cardiovascular disease with diabetes.

Patients with diabetes mellitus (DM) are at higher risk of cardiovascular events, particularly acute myocardial infarction (MI). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can improve cardiac outcomes among heart failure individuals, however, the effects on acute myocardial infarction remain unclear. This meta-analysis investigates the impact of empagliflozin in diabetic patients following acute myocardial infarction. We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science through August 10th, 2023. We included studies comparing empagliflozin versus placebo in diabetes patients with acute myocardial infarction. We used Revman to report the data as mean difference (MD) and 95% confidence interval (CI), and our effect size with a random effects model. Additionally, we performed Trial Sequential Analysis (TSA) to test the robustness of the results. The study protocol was published on PROSPERO with ID: CRD42023447733. Five studies with a total of 751 patients were included in our analysis. Empagliflozin was effective to improve LVEF% (MD: 1.80, 95% CI [0.50, 3.10], p = 0.007), left ventricular end-diastolic volume (LVEDV) (MD: -9.93, 95% CI [-16.07, -3.80], p = 0.002), and left ventricular end-systolic volume (LVESV) (MD: -7.91, 95% CI [-11.93, -3.88], p = 0.0001). However, there was no difference between empagliflozin and placebo groups in terms of NT-pro BNP (MD: - 136.59, 95% CI [-293.43, 20.25], p = 0.09), and HbA1c (MD: -0.72, 95% CI [-1.73, 0.29], p = 0.16). Additionally, empagliflozin did not prevent hospitalization due to heart failure (RR: 0.59, 95% CI [0.16, 2.24], p = 0.44, I-squared = 0%), and mortality (RR: 1.34, 95% CI [0.15,11.90], p = 0.79, I-squared = 25%). Empagliflozin initiation in diabetic patients following acute MI may improve echocardiographic parameters. However, empagliflozin might not be effective in heart failure prevention and optimal glycemic control in this patient population. Further large-scale trials are warranted to ascertain our findings.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.

OBJECTIVE: Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM).
METHODS: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis.
RESULTS: Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i were associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i.
CONCLUSIONS: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i.

BACKGROUND: Dapagliflozin and empagliflozin are antidiabetic medications. They are the first two sodium-glucose cotransporter-2 inhibitors (SGLT2i) to receive the US Food and Drug Administration approval to manage heart failure. Emerging new trials have examined changes in the 6-min walk distance as a clinically significant response to dapagliflozin and empagliflozin in patients with heart failure with reduced ejection fraction (HFpEF) and heart failure with preserved ejection fraction (HFrEF). This meta-analysis aims to evaluate the effects of dapagliflozin and empagliflozin on the 6-min walk distance in patients with HFpEF and HFrEF. To our knowledge, no such meta-analysis has been published.
METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) to identify eligible studies reported up to December 16, 2023. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). A p-value ≤ 0.05 is considered as statistically significant.
RESULTS: The meta-analysis included a total of 8 studies with 2624 patients. Overall, the results showed insignificant differences in the 6-min walk between the SGLT2i and placebo (MD 24, 95% CI -0.30 to 18.78, p = 0.06). Results became significant after resolving the heterogeneity (MD 6.72, 95% CI 0.13 to 13.31, p = 0.05). Notably, the results of each drug separately were insignificant. More robust observations occurred in the HFpEF group (MD 10.73, 95% CI 1.08 to 20.39, p = 0.03). Compared to placebo, patients on dapagliflozin reported significant improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary (KCCQ-CS) and Overall Summary (KCCQ-OS) with values of MD 5.18 (95% CI 2.80 to 7.57, p < 0.0001) and MD 4.06 (95% CI 1.66 to 6.46, p = 0.0009), respectively. The dapagliflozin group and patients with HFpEF had reported a significant reduction in their weight compared with the control group (MD -0.59 CI -1.09 to -0.08, p = 0.02) and (MD -0.80 CI -1.47 to -0.13, p = 0.02), respectively. No significant side effects were observed for dapagliflozin or empagliflozin.
CONCLUSIONS: Patients with HFpEF experienced benefits from SGLT2i administration, as evidenced by improved 6-min walk distances and weight reduction. Dapagliflozin demonstrated clinical and overall improvements in KCCQ scores and was more effective in reducing weight than the placebo. Both Dapagliflozin and Empagliflozin were well-tolerated and exhibited favorable safety profiles. Future studies could benefit from a larger patient population, a longer follow-up period, and a broader range of SGLT2i.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA). The clinical data regarding the use of SGLT2i and its potential side effects in oncology patients is limited. We are retrospectively reporting four oncology patients with type 2 diabetes mellitus using SGLT2i who were admitted with DKA. The mean age of the patients was 61.25 years, and male to female ratio was 1:1. The duration of type 2 diabetes ranged from 10 to 20 years (mean 15.75 years) and the types of SGLT2i used were empagliflozin 25 mg and dapagliflozin 10 mg. The types of malignancy in our case series included squamous cell carcinoma of the cheek, ovarian cancer, and two patients had laryngeal carcinoma (squamous cell carcinoma). Diabetic ketoacidosis was diagnosed in three patients following chemotherapy or concurrent chemo-radiotherapy. Poor oral intake and infections were the main risk factors in our patients. Mean blood glucose level, anion gap, and bicarbonate level were 11.7 mmol/l, 32.25, and 5 mmol/l, respectively. The majority had moderate DKA based on pH (mean 7.13). The hospital course was complicated by acute kidney injury (n=4), infections (n=4) (urinary tract infections, and pneumonia), and three patients required critical care. The mean length of hospitalization was 19.2 days and no mortality was reported among our patients. SGLT2i-related DKA is an emerging complication recognized in oncology patients. Some of the risk factors for this complication are starvation, poor oral intake, and infection which are quite prevalent in oncology patients. Temporary holding of SGLT2i medication during this period might have a potential preventive role.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce morbidity and mortality for heart failure (HF) patients and are recommended as cornerstones for their medical therapy. Utilization in clinical practice remains low for multiple reasons, one of which may be adverse events. We investigated the incidence of these events to see if they are associated with SGLT2i use. A systematic search was performed in databases, including PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and WHO\'s International Clinical Trials Registry Platform. Relevant randomized controlled trial studies assessing the safety outcomes of SGLT2i in HF patients were included in this study. We conducted the common-effect meta-analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of safety outcomes in SGLT2i compared with placebo. Eighteen studies were included in the meta-analysis composed of 12 925 HF patients taking an SGLT2i and 12 747 taking a placebo. The meta-analysis indicated that the all-cause mortality and serious adverse events (SAEs) were lower in the SGLT2i group (RR, 0.91; 95% CI, 0.85-0.97; P = 0.005, I2 = 0%; and RR, 0.92; 95% CI, 0.90-0.95; P < 0.001, I2 = 43%, respectively). Volume depletion and genitourinary infections were more prevalent in the SGLT2i group (RR, 1.17; 95% CI, 1.06-1.28; P = 0.001, I2 = 0%; and RR, 1.27; 95% CI, 1.13-1.43; P < 0.001, I2 = 17%, respectively). Our meta-analysis demonstrated that using SGLT2is in HF patients was correlated with reduced mortality and SAEs, with a more prominent effect in HF with reduced ejection fraction patients and those taking dapagliflozin.

UNASSIGNED: Obesity is a chronic disease with a myriad of complications including cardiovascular disease. There is a growing interest to examine if obesity treatment is associated with cardiovascular outcomes.
UNASSIGNED: In this narrative review, we focused on randomized controlled trials (RCT) with cardiovascular outcomes (CVO) from lifestyle intervention, bariatric surgery, glucagon-like peptide-1 analogues (GLP-1a) and other pharmacotherapy. Additionally, we provide a comprehensive look into the RCT of sodium glucose cotransporter 2 inhibitors (SGLT2i) and CVO in obesity, while also summarizing several ongoing randomized cardiovascular outcome controlled trials for the pharmacological treatment of obesity.
UNASSIGNED: To date, the results from the randomized controlled trials supported the association between obesity treatment and cardiovascular outcomes. Studies have large sample sizes, conducted over long duration, with the majority demonstrating superiority in primary cardiovascular outcome end points compared to placebo.
UNASSIGNED: Future data from several ongoing anti-obesity medications cardiovascular outcome trials such as SELECT, SURPASS, SUMMIT and SURMOUNT-MMO hold promises. Further studies are warranted to investigate the long term cardiovascular outcomes following lifestyle intervention and bariatric surgery.