Prescription patterns of SGLT2 inhibitors in patients with type 2 diabetes and heart failure with reduced ejection fracture admitted to a tertiary care centre in Ontario, Canada.

OBJECTIVE: To assess early adoption patterns of SGLT2 inhibitors (SGLT2i) in eligible patients with type 2 diabetes (T2DM) and heart failure with reduced ejection fracture (HFrEF) and identify gaps in practice. METHODS: A retrospective chart review of patients with T2DM and HFrEF admitted with decompensated heart failure to The Ottawa Hospital under Cardiology or GIM from June 2019-May 2021 was conducted. Patterns were assessed at 8-months intervals (1 period before the release of Diabetes Canada 2020 guidelines and 2 periods afterwards). Baseline patient characteristics, co-morbidities and prescriber information was collected. RESULTS: Of the 98 patients that met the inclusion criteria, 36.7% had a prescription for an SGLT2i either on admission, discharge or follow-up. Trends showed a gradual increase over time. On admission, 9.8% of patients were on an SGLT2i in period 1, 19.2% in period 2 and 23.3% in period 3. Patients receiving a prescription for SGLT2i on discharge were 0.0% in period 1, 10.0% in period 2 and 9.5% in period 3, all which were admitted under Cardiology. On follow-up, 13.9% of eligible patients were started on an SGLT2i in period 1, 21.1% in period 2 and 35.0% in period 3. Endocrinology was the main prescriber of SGLT2i in the outpatient setting, followed by Cardiology. CONCLUSIONS: Overall, trends show a slow but steady increase in early prescriptions of SGLT2i. However, most eligible patients were not started on therapy during our study period with variability in practice between specialties, highlighting opportunities to boost uptake in the future.

Progress of SGLT2 inhibitors in the treatment of common immune-related nephropathies.

The immune system can lead to a variety of renal diseases through direct or indirect mechanisms. In immune-mediated nephropathy, though standardized treatment, there are still a small number of patients with further decline in renal function, which may even progress to renal failure; sodium-glucose cotransporter protein 2 (SLC5A2,SGLT2) inhibitors not only can significantly reduce blood glucose, but also have an additional protective effect on the kidneys and the heart; this review concludes the potential mechanism of the renal protective effect of SGLT2i and the new advances in the recent years in common immune-mediated nephropathies, which can provide new theoretical references to optimize the therapeutic strategy of common immune-mediated nephropathies.

General physicians' perspectives on SGLT2 inhibitors for heart failure.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are novel agents for heart failure (HF) and are now recommended in guidelines. Understanding general physicians' perspectives can help to optimise utilisation of this new medication. AIM: To understand the clinical concerns and barriers from general physicians about prescribing SGLT2is in a general medicine cohort. METHODS: A questionnaire exploring clinicians' experience, comfort level and barriers to prescribing SGLT2is in patients with HF, incorporating two clinical scenarios, was disseminated to Internal Medicine Society of Australia and New Zealand members over a 2-month period. RESULTS: Ninety-eight participants responded to the questionnaire (10.8% response rate). Most respondents (66.3%) were senior medical staff. Most participants worked in metropolitan settings (64.3%) and in public hospital settings (83.7%). For HF with reduced ejection fraction, 23.5% of participants reported prescribing SGLT2is frequently (defined as prescribing SGLT2is frequently over 75% of occasions). For HF with preserved ejection fraction, 57.1% of participants reported prescribing SGLT2is less than 25% of the time. Almost half of the participants (44%) expressed a high level of familiarity with therapeutic knowledge of SGLT2is, while 47% indicated high familiarity with potential side effects. Patient complexity, cost of medications and discontinuity of care were identified as important barriers. Euglycemic diabetic ketoacidosis was the side effect that caused the most hesitancy to prescribe SGLT2is in 48% of the respondents. CONCLUSION: General physicians in Australia and Aotearoa New Zealand are familiar with the therapeutic knowledge and side effects of SGLT2is. Patient complexity, medication cost and discontinuity of care were significant barriers to the use of SGLT2is for HF among general physicians.

Heterogeneous treatment effects of sodium-glucose cotransporter 2 inhibitors on risk of dementia in people with type 2 diabetes: A population-based cohort study.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

Are Sodium-Glucose Cotransporter-2 Inhibitors the Cherry on Top of Cardio-Oncology Care?

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery: Rationale and design of the EMPOAF trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common types of acute AF and can complicate the treatment course of approximately one third of patients undergoing cardiac surgery. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are among the newest antidiabetic drugs which can be therapeutic options for preventing POAF by different mechanisms. METHODS: Empagliflozin to Prevent POAF (EMPOAF) is an interventional, investigator-initiated, double-blind, placebo-controlled, multicenter, randomized controlled trial which will be conducted in two referral teaching cardiology hospitals in Tehran. Four-hundred ninety-two adult patients who are scheduled for elective isolated coronary artery bypass graft (CABG) surgery will be randomly assigned to one of the groups of intervention (empagliflozin 10 mg daily) or placebo starting at least 3 days before surgery until discharge. Key exclusion criteria are a history of diabetes mellitus, AF, ketoacidosis, or recurrent urinary tract infections along with severe renal or hepatic impairment, unstable hemodynamics, and patients receiving SGLT2 inhibitors for another indication. The primary outcome will be the incidence of POAF. Key secondary endpoints will be the composite rate of life-threatening arrhythmias, postoperative acute kidney injury, hospitalization length, in-hospital mortality, stroke, and systemic embolization. Key safety endpoints will be the rate of life-threatening and/or genitourinary tract infections, hypoglycemia, and ketoacidosis. CONCLUSIONS: EMPOAF will prospectively evaluate whether empagliflozin 10 mg daily can reduce the rate of POAF in patients undergoing elective CABG. Enrolment into this study has started by November 2023 and is expected to be ended before the end of 2025.

Sodium-Glucose Cotransporter Type 2 Inhibitors Use in Elderly Polypathological Patients with Acute Heart Failure: PROFUND-IC Registry.

Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods: A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan-Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is (p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure.

Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

The Role of Sodium-Glucose Co-transporter 2 Inhibitors in Patients With Hypomagnesemia: A Systematic Review.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes, have demonstrated benefits in reducing heart failure hospitalizations, slowing chronic kidney disease, and decreasing major cardiovascular events. Recent studies have shown that SGLT2 inhibitors can elevate serum magnesium levels in patients with type 2 diabetes, suggesting potential benefits in managing refractory hypomagnesemia. This systematic review analyzed relevant case reports, observational studies, and randomized controlled trials (RCTs) to investigate the association between SGLT2 inhibitors and hypomagnesemia. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality was assessed using the CAse REport (CARE) guidelines. It encompassed four case reports, one retrospective observational study, one post-hoc analysis of 10 RCTs, and one meta-analysis of 18 RCTs, with a total study population of 19,767 patients. The meta-analysis revealed that SGLT2 inhibitors significantly increased serum magnesium levels in patients with type 2 diabetes, with a linear dose-dependent increase noted particularly for canagliflozin. Additionally, the case reports and other studies suggested that SGLT2 inhibitors could exert extraglycemic effects, potentially enhancing magnesium balance beyond their impact on urinary magnesium excretion. This systematic review underscores the effectiveness of SGLT2 inhibitors in addressing refractory hypomagnesemia linked with urinary magnesium wasting. It also suggests promising avenues for the application of these drugs in diverse patient populations.

Empagliflozin-Associated Pancreatitis in the Setting of Hyperglycemic Hyperosmolar Syndrome.

Acute pancreatitis is a prevalent gastrointestinal condition in the United States, with approximately 130,000 new cases annually, displaying a rising incidence. Severe cases, constituting 20% of instances, necessitate intensive care unit admission, associated with elevated mortality rates. While gallstones and chronic alcohol use are primary causes, certain medications, including ACE inhibitors, statins, hormone-replacement therapies, diuretics, hypoglycemic agents, and steroids, can induce pancreatitis. Notably, recent reports link empagliflozin, an SGLT-2 inhibitor used in managing type 2 diabetes, to pancreatitis, a rare complication in this drug class. This article details a case study of a 57-year-old African American man presenting with hyperglycemic hyperosmolar syndrome due to empagliflozin-induced pancreatitis, a novel sequela. The discussion underscores the role of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in diabetes management, emphasizing their advantages and associated complications. This report adds a unique dimension to the literature, emphasizing the importance of prompt identification and cessation of culpable agents to prevent adverse outcomes. This article aims to comprehensively address the prevalence and increasing incidence of acute pancreatitis in the United States. This report aims to assist healthcare professionals in recognizing and discontinuing causative agents, thereby providing valuable insights into the comprehension of drug-induced pancreatitis.

Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i.

BACKGROUND: Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans. METHODS: Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications. RESULTS: Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses. CONCLUSION: This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.

Association between clinical and laboratory factors and response to sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: a retrospective observational study.

BACKGROUND: This study aimed to investigate the association between clinical and laboratory parameters and response to therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: We retrospectively analyzed the medical records of people with T2D in whom SGLT2i was started. Clinical and laboratory parameters were recorded before, 3 and 6 months after starting treatment. Specific criteria were applied to classify participants into good and poor responders in terms of weight loss (primary outcome) and glycemic control (secondary outcome), separately. RESULTS: Fifty individuals (64% men) with a mean age of 65.8 ± 8.5 years were included in the analysis. 86% and 64% of the participants were classified into good response categories for glycemic control and weight loss, respectively. Good responders in terms of glycemic control had lower high-density lipoprotein cholesterol levels at baseline compared to poor responders (43.3 vs 57.4 mg/dl, p = 0.044). In the logistic regression analysis, a higher baseline weight was associated with a better response to therapy in terms of weight loss (p = 0.04). CONCLUSIONS: Our findings suggest that specific clinical and laboratory parameters are associated with response to SGLT2i treatment and can contribute to a more personalized approach to T2D care.

Comparative cardiovascular and renal effectiveness of empagliflozin and dapagliflozin: scandinavian cohort study.

AIMS: To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice. METHODS: Cohort study using data from nationwide registers in Sweden, Denmark and Norway, from June 2014 to June 2021 including 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death and diabetic ketoacidosis. RESULTS: Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events (adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, [95% CI 0.97-1.08]), heart failure (6.5 vs. 6.3 events per 1000 person-years; HR 1.05 [0.97-1.14]) and serious renal events (3.7 vs. 4.1 events per 1000 person-years; HR 0.97 [0.87-1.07]). In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis. CONCLUSIONS: Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality and diabetic ketoacidosis.

Research progress on the effects of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome. / SGLT2æŠ‘åˆ¶å‰‚å¯¹ä»£è°¢ç»¼åˆå¾ç›¸å ³ä»£è°¢ç´Šä¹±çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Metabolic syndrome (MS) is a complex group of metabolic disorders with an increasing global incidence rate, posing a serious threat to human health. Currently, there is no specific effective drug for its clinical treatment. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new class of oral hypoglycemic drugs. They not only promote urinary glucose excretion by inhibiting the reabsorption of glucose by renal proximal convoluted tubule epithelial cells, thereby reducing blood glucose in a non-insulin-dependent manner, but also reduce blood glucose by improving the function of islet ß cells, reducing inflammatory responses, and inhibiting oxidative stress. In addition, SGLT2 inhibitors can also reduce body weight through osmotic diuresis and increased fat metabolism; reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and improving vascular function; improve blood lipids by increasing degradation of triglyceride; reduce blood uric acid by promoting uric acid excretion in kidney and intestine and reducing uric acid synthesis. Therefore, this article reviews the improvement effects of SGLT2 inhibitors on multiple metabolic disorders in MS and its related regulatory mechanisms.

New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions.

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future.

Type Disparity in Sodium-Glucose Cotransporter-2 Inhibitors in Incidences of Renal Cell Carcinoma: A Propensity-Score-Matched Cohort Study.

(1) Background: Recently, sodium-glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to significantly reduce renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) or heart failure is unclear. We conducted an observational analysis to explore type disparity in the prescription of SGLT2Is on RCC risk. (2) Methods: A nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2021) was conducted. Patients aged ≥40 years who took SGLT2Is were designated as the SGLT2I group, whereas propensity score 1:1-matched randomly selected patients without SGLT2Is were assigned to the non-SGLT2I group. The primary outcome was the risk of incident RCC between individual SGLT2Is. Multiple Cox regression modeling was conducted to analyze the association between individual SGLT2I use and RCC risk. (3) Results: After a 5.5-year follow-up, SGLT2I use was associated with a significantly lower risk of incident RCC (hazard: 0.62; 95% confidence interval [CI]: 0.44-0.89). Compared with non-users and after adjusting for the index year, sex, age, comorbidities, concurrent medication, and the risk of developing RCC, the hazard ratios of dapagliflozin, canagliflozin, and empagliflozin were 0.66 (95% CI: 0.53-0.83), 0.84 (95% CI: 0.46-1.30), and 0.71 (95% CI: 0.56-0.90), respectively. (4) Conclusions: Our data show a type-based effect of SGLT2Is on RCC risk. The type-based effect of SGLT2Is should be further studied for better clinical management information and for reducing RCC incidence in patients with T2D.

SGLT2 inhibitors as a potential therapeutic option for pulmonary hypertension: mechanisms and clinical perspectives.

Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.

Sodium-glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure.

Background: Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes. Methods: We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes. Results: A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), p = 0.046]. Conclusion: The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.

Cardiovascular Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHODS: This systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m². RESULTS: Nine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04). CONCLUSIONS: Compared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023401081.