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Background: Many studies reported a renal protection by sodium glucose cotransporter-2 inhibitor (SGLT2i) using in Type 2 diabetes mellitus (T2DM). Objective: Our study was designed to evaluate the renal benefit offered by SGLT2 inhibitor (dapagliflozin) in type 2 diabetic patients. Patients and Methods: 100 diabetic patients, 50 treated by dapagliflozin 10 mg once daily for 12 months and 50 treated by placebo for the same period. Patients were recruited from those attending Endocrinology Unit in Benha University Hospital. Clinical and laboratory data were performed to patients who were followed up every 3 months for 1 year. Results: No significant difference among the two groups regarding age, sex, residence, and the common adverse effects. Urinary albumin/creatinine ratio was statistically lower in SGLT2i group compared to placebo group at the end of the study but was non-significant at base line. Estimated glomerular filtration rate (eGFR) was statistically higher in SGLT2i group compared to placebo group at the end of the study although there was non-significant difference at base line. No significant difference between the two groups regarding HbA1c at base line, 3 and 6 months later but was statistically lower in SGLT2i group after 9 months and 1 year. BMI, SBP and DBP were statistically lower in SGLT2i group at the end of the study but there was non-significant difference at base line. Conclusion: We found reno protective properties by using sodium glucose cotransporter-2 inhibitor (dapagliflozin) in type 2 diabetic patients, a great impact on glycemic control and other pleiotropic effects without significant differences regarding common adverse effects. [ABSTRACT FROM AUTHOR]

Morbidity and mortality associated with heart failure (HF) has remained high despite advances in therapy. Furthermore, HF-associated risk in patients with type 2 diabetes mellitus (T2D) is even higher than in patients without T2D owing to the strong reciprocal relationship between conditions. However, until recently, no therapy to treat patients with diabetes also reduced cardiovascular risks related to HF. Recent clinical studies (DAPA-HF, EMPEROR-Reduced and EMPEROR-Preserved, SOLOIST-WHF trial) and meta-analysis have demonstrated that sodium–glucose cotransporter-2 inhibitors (SGLT2i) are among the first antidiabetic drugs capable of reducing cardiovascular risks related to HF and improving the prognosis of patients with and without diabetes. Their pleiotropic mechanisms of action place them at the intersection of hemodynamic, metabolic, and neurohumoral pathways, with clear advantages for treating these patients independent of its glucose-lowering effect. Moreover, the benefits of SGLT2i were consistent across the cardiorenal continuum in different populations and clinical settings, which has led to different guidelines introducing SGLT2i as a first-line treatment for HF. [ABSTRACT FROM AUTHOR]

The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium–glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly benefit cardiac function through multifaceted interorgan cross talk, which can break the cardiorenal vicious circle linked to T2D. In this article, we briefly review the different mechanisms of action that may explain the renal beneficial effects of SGLT2i and disclose the results of the key renal outcome trials and the subsequent update of related clinical guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies suggest that sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective at slowing the progression of kidney disease and lowering the risk of kidney failure in people with kidney disease and type 2 diabetes. There is no such study from India. The present study was performed to evaluate the effects of SGLT2i in Indian patients with diabetes and chronic kidney disease (CKD). Materials and Methods: This prospective study included 86 patients with diabetes and chronic kidney disease and with an estimated creatinine clearance of >30 mL/minute. Forty-one patients received SGLT2i and 45 patients did not receive SGLT2i. Patients were followed up for at least 12 months. Body mass index (BMI), blood pressure, HbA1c, urine protein to creatinine ratio (UPCR), doubling of serum creatinine and rate of decline of the estimated creatinine clearance were compared between the two groups. Results: The two groups were comparable at baseline in terms of age, sex, blood pressure, BMI, HbA1c, and degree of renal impairment. Over 12 months the UPCR decreased by 0.03 in SGLT2i group and increased by 1.1 in non SGLT2i group (P < 0.05). Doubling of serum creatinine occurred in 4.8% of patients in the SGLT2i group as compared to 18% in the control group (P < 0.05). The rate of decline of the estimated creatinine clearance in the SGLT2i group was 4.9 ml/min/year as compared to 9.4 ml/min/year in the non SGLT2i group (P < 0.05). At 12 months the BMI in the SGLT2i group decreased by 1.49 as compared to 0.12 in the non SGLT2i group (P < 0.05). The blood pressure and HbA1c control were similar in both groups during the study period suggesting that the observed effect was due to SGLT2 inhibition itself and not due to blood pressure or blood glucose control. Conclusion: Our study showed that treatment with SGLT2i had significant renoprotective effects, as shown by a reduction in urinary protein excretion, less percentage of patients developing doubling of serum creatinine, and a slower rate of decline in creatinine clearance. [ABSTRACT FROM AUTHOR]

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) prevent heart failure (HF) in patients with type 2 diabetes mellitus (T2DM) but prescription rates are low. The effect of an electronic health record (EHR) alert notifying providers of patients' estimated risk of developing HF on SGTL2i prescriptions is unknown., Methods: This was a pragmatic, randomized clinical trial that compared an EHR alert and usual care among patients with T2DM and no history of HF or SGLT2i use at a single center. The EHR alert notified providers of their patient's HF risk and recommended HF prevention strategies. Randomization was performed at the provider level across general and subspecialty internal medicine as well as family medicine outpatient clinics. The primary outcome was proportion of SGLT2i prescriptions within 30 days. Proportion of natriuretic peptide (NP) tests within 90 days was also assessed., Results: A total of 1524 patients (median age 75 years, 45% women, 23% Black) were enrolled between September 28, 2021, and April 29, 2022 from 189 outpatient clinics. SGLT2i were prescribed to 1.2% (9/780) of patients in the EHR alert group and 0% (0/744) of those in the usual care group ( P value = 0.009). Natriuretic peptide testing was performed within 90 days among 10.8% (84/780) of patients in the EHR alert group and 7.3% (54/744) of patients in the usual care group ( P value = 0.02)., Conclusions: In a single-center trial with low overall SGLT2i use, an EHR alert incorporating HF risk information significantly increased SGLT2i prescriptions and NP testing although the absolute rates were low., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MWS has received personal fees from Merck and serves on the advisory board at descendants DNA. KVP has received consultant fees from NovoNordisk. NK has received consultant fees from HeartSciences and Tricog Health. AP received grant funding outside this study from National Institute of Health, Gilead Sciences, Ultromics, Roche Diagnostics, and Applied Therapeutics; has received honoraria outside of this study as an advisor/consultant for Tricog Health Inc, Lilly, USA, Rivus, Roche Diagnostics, Axon Therapies, Semler Scientific, Medtronic, Edwards Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharamcuticals, Emmi Solutions, Palomarin Inc (Stocks compensation) and has received nonfinancial support from Pfizer and Merck. All other authors declare no competing interests.

Background: Vericiguat has demonstrated efficacy in improving the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical deterioration. However, its real-world impact on reducing N-terminal B-type natriuretic peptide (NT-proBNP) levels and improving ventricular remodeling remains uncertain in stable HFrEF patients receiving guideline-directed medical therapy (GDMT) over the short term., Methods: This multicenter, observational cohort study included 200 HFrEF patients. Patients were grouped based on their preference for vericiguat use. We evaluated the impact of vericiguat on HFrEF patients by analyzing the difference in the proportion of patients with NT-proBNP levels ≤1000 pg/ml between two groups after a 6-month follow-up, using logistic regression and covariance analysis. Changes in echocardiographic parameters, left ventricular reverse remodeling (LVRR) ratio, and safety outcomes were also evaluated., Results: During the 6-month follow-up, 105 patients (82.68 %) in the vericiguat group and 46 patients (63.01 %) in the control group reached the primary endpoint. Multivariate logistic regression confirmed vericiguat as a significant factor in reducing NT-proBNP levels (Model 2: odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.24-5.77, P = 0.013), but it showed no significant association with LVRR (Model 2: OR = 0.52, 95 % CI: 0.24-1.13, P = 0.097). The safety analysis indicated a higher incidence of mild to moderate gastrointestinal symptoms in the vericiguat group compared to the control group (23.62 % vs. 2.74 %, P < 0.001)., Conclusions: Vericiguat significantly reduced NT-proBNP levels in patients with chronic HErEF under GDMT but was ineffective for LVRR during the 6-month follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Despite sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor/neprilysin inhibitors (ARNi) being cost-effective evidenced-based therapies for the management of Heart Failure with Reduced Ejection Fraction (HFrEF), research shows that less than 30% of patients with HFrEF are prescribed these agents., Objective: This study aimed to understand clinician-perceived barriers and facilitators to prescribing ARNi and SGLT2i in patients with HFrEF., Methods: We conducted virtual and in-person semi-structured interviews in a large integrated healthcare delivery system in the United States. Twenty cardiology clinicians managing patients with HFrEF were recruited using purposeful sampling to target providers across professions and practice sites. The interview guide was developed based on a literature review and insights from a practicing cardiologist. It inquired about perceived prescribing behaviors, focusing on factors affecting the use of ARNi and SGLT2i. We identified key themes using rapid qualitative analysis., Results: Twenty clinicians were interviewed: 13 physicians, five advanced practitioners, and two clinic-based pharmacists. Eighteen interviews were analyzed; we excluded two as the clinicians interviewed did not meet the inclusion criteria. Three major themes were identified: 1) clinician-reported prescribing patterns don't always align with the American College of Cardiology/American Heart Association guidelines for the use of SGLT2i and ARNi due to clinical inertia, lack of familiarity, knowledge, and comfort with use, and concerns over polypharmacy or adverse events, 2) clinician-perceived and actual out-of-pocket cost reduced prescribing of ARNi or SGLT2i to patients, exacerbated by a lack of visibility into patients' prescription coverage, denials of coverage by insurance, and navigating prior authorization related workflows, and 3) incorporation of a clinic-based pharmacist increased the prescribing of these medications., Conclusions: Increasing cost transparency, implementing interventions to overcome clinical inertia and cost hurdles, and increasing clinic-based pharmacist support may improve evidenced-based prescribing in patients with HFrEF, especially for comparatively novel classes such as ARNi and SGLT2i., (Copyright © 2024. Published by Elsevier Inc.)

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a novel class of oral antidiabetic agents with proven cardiovascular and mortality benefits. By promoting glucosuria, SGLT2Is increase the risk of genital and urinary tract infections (UTIs), which remain uncomplicated in most cases. Comparative studies detailing the gender differences in the clinical profile of SGLT2I-related UTIs (SUTIs) are lacking. Hence, this study was designed to investigate the gender-related differences in the clinical profile of SUTIs. Methodology This prospective study enrolled 100 consecutive diabetes mellitus patients with UTI symptoms who were on SGLT2Is. In addition to collecting clinical details, patients were subjected to the following investigations: complete blood counts, urea, creatine, liver function, lipid components, urine analysis, urine culture, and ultrasonography. Results Females (n = 80) outnumbered males (n = 20). Although females were younger than males (53.68 ± 10.26 vs. 63.30 ± 10.75 years, p = 0.003), body mass index (29.84 ± 7.22 vs. 24.62 ± 3.10 kg/m 2 , p = 0.008) and waist circumference (103.01 ± 14.49 vs. 93.75 ± 4.50 cm, p = 0.109) were higher in females. About 22.5% of females had undergone hysterectomy. The mean duration of diabetes mellitus was longer in males (10.64 ± 6.74 vs. 7.78 ± 4.75 years), whereas the median duration of SGLT2I use (4 (interquartile range (IQR) = 1-12) vs. 3 (IQR = 2-4) months) and mean HbA1c levels were not different between the two groups. A greater proportion of males were complicated by retinopathy (55% vs. 15%) and proteinuria (65% vs. 17.5%), while neuropathy (85% vs. 71.25%) rates were similar. Overall, 35% of males had complicated UTIs (renal abscess, pyelonephritis, prostatic abscess) compared to only 3.75% of females (p = 0.001). Conclusions The majority of SUTIs are uncomplicated in females whereas in males one-third are complicated infections. Although females with SUTI had a higher prevalence of obesity and dyslipidemia, males had a longer duration of diabetes mellitus and higher retinopathy prevalence. Extreme caution should be exercised in patients at risk for SUTI before prescribing SGLT2I., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board, Government Medical College, Srinagar issued approval IRBGMC-SGR/Endo/512. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bhat et al.)

Background: Cardiac remodeling is an adverse phenomenon linked to heart failure (HF) progression. Cardiac remodeling could represent the real therapeutic goal in the treatment of patients with HF and reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as ACEi/ARBs and β-blockers with anti-remodeling effects. More recently, ARNI effects on cardiac remodeling were also demonstrated; additional potential benefits of gliflozins remain non clearly demonstrated., Aim of Study: To evaluate possible changes in cardiac remodeling in patients with HFrEF/HFmrEF in treatment with ARNI or ARNI plus SGLT2i and the potential benefit on cardiac remodeling of adding SGLT2i to ARNI., Methods: Between June 2021 and August 2023, 100 consecutive patients with HFrEF/HFmrEF underwent conventional and advanced echocardiography (TDI, 2DSTE): patients were therefore divided into three groups according to therapy with neither ARNI nor SGLT2i, just ARNI or both. After 3 months, all patients underwent echocardiographic follow-up., Results: After a 3 months of therapy, significant improvements were observed for LVEF, LVEDD, LVEDV, LVESV, LV mass, E/e', LV GLS, TAPSE (ANOVA p< 0.01 in all cases), RV S' velocity (ANOVA p< 0.001).The trend in favor of additional treatment with SGTL2i over ARNI remained statistically significant even after multivariable analysis (p< 0.001 for LVEF, LVEDD; p< 0.01 for LV GLS, TAPSE, TRVS; p< 0.05 for LV mass)., Conclusions: SGLT2i therapy when added to the standard treatment for HFrEF and HFmrEF is associated with an improved biventricular function and ventricular dimensions at follow-up., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown., Objective: We investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation., Methods: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups on the basis of the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n = 368) and non-SGLT2i using (n = 368) in each group. The primary outcome was AF recurrence after a 3-month blanking period., Results: During a total of 1315 person-years of follow-up, AF recurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted hazard ratio, 0.56; 95% CI, 0.43-0.74; P < .001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted hazard ratio, 0.58; 95% CI, 0.41-0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups., Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF., Competing Interests: Disclosures Changsheng Ma has received honoraria for presentations from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, and Pfizer. Jianzeng Dong has received honoraria for presentations from Johnson & Johnson., (Copyright © 2024. Published by Elsevier Inc.)

Integrating sodium-glucose co-transporter 2 inhibitors (SGLT2i) into the treatment for chronic kidney disease (CKD) has marked a significant therapeutic advance in nephrology. Clinical trials such as DAPA-CKD and EMPA-KIDNEY have demonstrated the beneficial effects of SGLT2i in slowing CKD progression and reducing proteinuria. However, the applicability of these results to patients with glomerulonephritis is still unresolved due to various limitations. This manuscript combines the evidence supporting the use of SGLT2i in glomerular diseases, highlights the limitations and strikes a conclusive balance on their role in clinical practice., Competing Interests: F.C.-F. reports fees from Novartis, Apellis, SOBI and AstraZeneca, outside the submitted work. M.P. reports fees from Alexion, Apellis, Vifor, GSK, Novartis, Otsuka, STADA and Travere, and loyalties from UpToDate. L.d.V. was a member of an Advisory Board for TRAVERE. She received speaker fees at meeting with indirect support from Vifor, Bayer, AstraZeneca, Boehriger, Amgen and Astella. She had been National leader for the PROTECT study with sparsentan and she is National Leader for the VISIONARY study with sibeprelimab. J.F. is the Editor-in-Chief of CKJ. C.Z. is member of the CKJ Editorial Board., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Inhibition of sodium-glucose cotransporter 2 (SGLT2) by empagliflozin (EMPA) and other "flozins" can improve glycemic control under conditions of diabetes and kidney disease. Though they act on the kidney, they also offer cardiovascular and liver protection. Previously, we found that EMPA decreased circulating triglycerides and hepatic lipid and cholesterol esters in male TallyHo mice fed a high-milk-fat diet (HMFD). The goal of this study was to determine whether the liver protection is associated with a change in metabolic function by characterizing the hepatic and circulating metabolic and lipidomic profiles using targeted LC-MS. In both male and female mice, HMFD feeding significantly altered the circulating and hepatic metabolome compared with low-fat diet (LFD). Addition of EMPA resulted in the restoration of circulating orotate (intermediate in pyrimidine biosynthesis) and hepatic dihydrofolate (intermediate in the folate and methionine cycles) levels in males and acylcarnitines in females. These changes were partially explained by altered expression of rate-limiting enzymes in these pathways. This metabolic signature was not detected when EMPA was incorporated into an LFD, suggesting that the restoration requires the metabolic shift that accompanies the HMFD. Notably, the HMFD increased expression of 18 of 20 circulating amino acids in males and 11 of 20 in females, and this pattern was reversed by EMPA. Finally, we confirmed that SGLT2 inhibition upregulates ketone bodies including β-hydroxybutyrate. Collectively, this study highlights the metabolic changes that occur with EMPA treatment, and sheds light on the possible mechanisms by which this drug offers liver and systemic protection. NEW & NOTEWORTHY Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, have emerged as a new treatment option for individuals with type 2 diabetes that have positive impacts on kidney and cardiovascular disease. However, less is known about their impact on other tissues, including the liver. Here, we report that empagliflozin reduces hepatic steatosis that is associated with restoring metabolic intermediates in the folate and pyrimidine biosynthesis pathways. These changes may lead to new approaches to treat nonalcoholic fatty liver disease.

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., Conclusion: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data., Methods: We conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation., Findings: Prior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74-0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001)., Implications: In this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population., Competing Interests: Declaration of competing interest UA has received honoraria from Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings. UA has also received investigator-led funding by Procter & Gamble. DJC has received investigator-led funding and conference support from Astra Zeneca, NovoNordisk and Perspectum. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals., Methods: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials., Results: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1612851.54 up to EUR 6587360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data., Conclusions: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Advanced heart failure (HF) is an epidemic that affects multiple organ systems with high morbidity and mortality rates despite optimal medical therapy (OMT) and remains the leading cause of hospitalizations in type 2 diabetes-related cardiovascular disease. The addition of sodium-glucose co-transporter inhibitors (SGLT2i) in treating these patients has seen improved mortality and hospital admission rates. As such, we felt it was important to investigate whether the use of SGLT2i improved functional capacity in patients with HF when compared to OMT by evaluating maximum oxygen consumption (peak VO 2 ) using cardiopulmonary exercise testing (CPET)., Methods: We found 94 heart failure patients between August 2020 and August 2021 who underwent CPET before and after treatment at Mayo Clinic in Florida. 50 patients received OMT and 44 received OMT and SGLT2i therapy. CPET results before and after were compared for each group., Results: The baseline ejection fraction was not significantly different between groups, with the OMT group at 38% and the SGLT2i group at 33%, p  = 0.10. OMT patients were found to have a significantly lower hemoglobin A1c of 5.7 (5.4-6.1) compared to those with SGLT2i therapy of 6.4 (5.8-7.1), p  = 0.01. The baseline peak VO 2 was 17.3 ml/kg/min (13.3-21.6) in the OMT group and 17.3 ml/kg/min (14.4-18.9) in the SGLT2i group, p  = 0.18, not significantly different. The interesting finding is that the follow-up peak VO 2 at one year for the OMT group was 17 ml/kg/min (13.3-21.6), which was not significantly different from the SGLT2i group peak VO 2 of 17 ml/kg/min (14.6-19.6), p  = 0.19. Our study is the first to compare before and after peak VO 2 values of the OMT+SGLT2i group to the patient's own baseline and we found no significant improvement., Conclusion: Our single-center data shows no improvement in functional capacity after the addition of SGLT2i therapy to OMT in patients with advanced heart failure. Improved hospitalization and symptoms may be attributed to other numerous effects of SGLT2i such as volume management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Desai, Sharma, Abuah, Jang, Desai, Paghdhar and Goswami.)

Introduction and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD)., Methods: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome., Results: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively)., Conclusions: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) have gained immense attention for a variety of indications. Limb amputations (LA) and fractures were reported in clinical trials. This network meta-analysis and meta-regression were carried out to quantify the risks of these events., Research Design and Methods: Randomized clinical trials evaluating SGLT2is and reporting patients developing LA/fracture were included. Odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. Sub-group analyses and meta-regression analysis were carried out., Results: Ninety articles were included (LA: 36 studies; 96522 participants and fracture: 66 studies; 102,862 participants). An increased risk of LA (OR: 1.2; 95% CI: 1.1, 1.3) was observed. Amongst SGLT2is, canagliflozin was associated with increased risk of LA (OR: 1.6, 95% CI: 1.1, 2.4) while dapagliflozin with fracture (OR: 1.1, 95% CI: 1, 1.2). Sub-group analysis revealed increased risk of LA with an OR of 1.3 among those in the age group of > 40 to < 65, body-mass index of > 30 kg/m 2 , HbA1c category of > 7%, duration of diabetes of > 10 years, type 2 diabetes, and an OR of 1.2 for SGLT2is administration of > 6 months., Conclusions: SGLT2is were observed with an increased risk of LA. High- risk categories were identified for which precautions should be recommended in the standard treatment guidelines., Protocol Registration: Open Science Framework (https://osf.io/5fwyk).

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy's potential effects on the risks of dementia and Parkinson's disease are not well established, with conflicting results based on observational studies. Hence, we sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson's disease in patients with type 2 diabetes mellitus, heart failure, or chronic kidney disease., Methods: We performed a systematic literature search on PubMed, and Clinicaltrial.gov for relevant randomized controlled trials from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model., Results: A total of 12 randomized controlled trials with 74,442 patients (40,784 in the SGLT2i group and 33,658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years, respectively. Pooled analysis showed that there is no significant association between SGLT2i use and the risk of dementia (OR 1.37; 95% CI, 0.70-2.69; P = .36), dementia Alzheimer's type (OR 1.99; 95% CI, 0.59-6.71; P = .27), vascular dementia (OR 0.40; 95% CI, 0.09-1.85; P = .24), and Parkinson's disease (OR 0.63; 95% CI, 0.25-1.61; P = .33) when compared with the control groups., Conclusion: Our study suggests that there is no significant association between SGLT2i use and the risk of dementia, its subtypes, and Parkinson's disease when compared with the control groups., (Copyright © 2024. Published by Elsevier Inc.)

Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower anthracycline-induced cardiotoxicity. Methods: PubMed and Google Scholar were searched until September 2023 for studies regarding SGLT2i for treating anthracycline-induced cardiotoxicity. Overall mortality and cardiovascular events were considered. Using a random-effects model, data pooled RR and HR at a 95% confidence interval (CI). Results: 3 cohort studies were identified, analyzing 2817 patients. Results display a significant reduction in overall mortality [RR = 0.52 (0.33-0.82); p  = 0.005; I 2 = 32%], HF hospitalization [RR = 0.20 (0.04-1.02); p  = 0.05; I 2 = 0%] and no significant reduction in HF incidence [RR = 0.50 (0.20-1.16); p  = 0.11, I 2 = 0%]. Conclusion: SGLT2i mitigates mortality and hospitalization due to heart failure, improving cancer patient's chances of survival by undergoing anthracycline treatment.

Background and Objectives: 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Diabetic nephropathy represents the leading cause of end-stage kidney disease in developed countries. Cardiovascular outcome trials have found that in participants who received a glucagon-like peptide-1 receptor agonist (GLP1RA) and a sodium-glucose cotransporter 2 inhibitor (SGLT2i), the risk of incidence and progression of diabetic nephropathy in type 2 diabetes mellitus was reduced. The aim of this study was to compare the decline in estimated glomerular filtration rate (eGFR) among people taking a GLP1RA with that among people taking an SGLT2i in a real-world setting., Methods: Data for 478 patients with type 2 diabetes mellitus who initiated therapy with a GLP1RA (n = 254) or an SGLT2i (n = 224) between January 1, 2018 and December 31, 2021 were extracted. The primary outcome was any reduction ≥30% in eGFR after the start of therapy. Weight loss and drug discontinuation were also assessed., Findings: Over a median follow-up of 24 months, an eGFR reduction ≥30% occurred in 34 of 254 patients (13.4%) starting a GLP1RA and in 26 of 223 patients (11.6%) starting an SGLT2i (hazard ratio = 0.89; 95% CI, 0.54-1.49; P = 0.67). Median eGFR change over the whole follow-up was similar between groups (SGLT2i: median, -2 mL/min/1.73 m 2 ; 25th, 75th percentile, -13, 8 mL/min/1.73 m 2 ; GLP1RA: median, 0 mL/min/1.73 m 2 ; 25th, 75th percentile, -10, 7 mL/min/1.73 m 2 ; P = 0.54). No worsening of kidney function was observed, even when considering the ratio eGFR mean. The value of eGFR at baseline indicated a statistically significant indirect correlation with the observed absolute value of eGFR change over the follow-up (ρ = -0.36; P < 0.001). The difference in eGFR changes over time observed by eGFR categories was statistically significant (P = 0.0001) in both treatment groups. No significant differences in weight loss and drug discontinuations were observed between groups., Implications: Although acting on different molecular mechanisms, both GLP1RA and SGLT2i might have similar effects on eGFR decline in diabetes, as suggested by the results of the present study conducted in a real-world setting. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc., Competing Interests: Declaration of competing interest E. Maddaloni reported personal speaker/consultancy fees from PikDare, Abbott, MTD, MSD, EliLilly, NovoNordisk, and Merck-Serono KgA and support for attending scientific meetings from Abbott and Theras. R. Buzzetti reported research grants from AstraZeneca and speaker/consultancy fees from EliLilly, Sanofi, Abbott, Vertex, NovoNordisk, Boehringer Ingheleim, AstraZeneca, Mundipharma, and Guidotti. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Abstract Background Randomized controlled trials showed that sodium/glucose cotransporter-2 inhibitors (SGLT2i) protect the heart and kidney in an array of populations with type 2 diabetes (T2D) and increased cardiorenal risk. However, the extent of these benefits also in lower kidney-risk T2D populations needs further investigation. Methods Members of Maccabi Healthcare Systems listed in their T2D registry who initiated new glucose lowering agents (GLA), were divided into SGLT2i initiators and other GLAs (oGLAs). Groups were propensity score-matched by baseline demographic and medical characteristics. Two composite cardiovascular outcomes were defined: all-cause mortality (ACM) or hospitalization for heart failure (hHF); and ACM, myocardial infraction (MI) or stroke. The cardiorenal outcome was: ACM, new end-stage kidney disease (ESKD) or ≥ 40% reduction from baseline estimated glomerular filtration rate (eGFR). Renal-specific outcome was new ESKD or ≥ 40% eGFR reduction. Single components of cardiovascular and kidney outcomes were also assessed. Three subgroup definitions of low baseline kidney-risk were used: eGFR > 90 ml/min/1.73 m2; urinary albumin below detectable levels; and low risk according to Kidney Disease: Improving Global Outcomes (KDIGO) classification. Analyses were performed utilizing an unadjusted model, and a model adjusted to baseline eGFR and urinary albumin-to-creatinine ratio. Results Between April 1, 2015 and June 30, 2018; 68,187 patients initiated new GLAs — 11,321 SGLT2i initiators and 42,077 oGLAs initiators were eligible. Propensity score-matching yielded two comparable cohorts; each included 9219 participants. Median follow-up was 1.7 years. Compared to oGLAs, SGLT2i initiators had lower incidence of ACM or hHF [HR95%CI = 0.62(0.51–0.75)]; ACM, MI or stroke [0.67(0.57–0.80)]; the cardiorenal outcome [0.65(0.56–0.76)]; and the renal-specific outcome [0.70(0.57–0.85)]. SGLT2i initiators also had lower risk for ACM, hHF and ≥ 30%, ≥ 40%, ≥ 50%, ≥ 57% eGFR reduction. No difference between groups was observed for MI or stroke. In the low baseline kidney-risk subgroups, SGLT2i initiation was generally associated with lower risk of the cardiovascular and cardiorenal outcomes, driven mainly by lower ACM incidence. Conclusions Our findings in the general population of patients with T2D demonstrates lower risk of cardiorenal outcomes associated with initiation of SGLT2i compared with oGLAs, including specifically in patients with low baseline kidney-risk.

Abstract Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p

Background: The Food and Drug Administration issued a warning on the risk of acute kidney injury and a signal of nephrolithiasis for patients using sodium–glucose co-transporter 2 inhibitors (SGLT2i). We performed a descriptive analysis on acute renal failure (ARF) and nephrolithiasis cases reported to SGLT2i in the VigiBase®, in the scope of characterizing the patients and reactions and to report on the disproportionality analysis.Methods: We analyzed all ARF and nephrolithiasis reports for SGLT2i in VigiBase from inception to September 2021. ARF cases were defined as reports containing at least one of the preferred terms (PTs) included in the ARF narrow Medical Dictionary for Regulatory Activities Standardised Queries (MedDRA SMQ). SGLT2i exposure was considered for reports with at least one gliflozin as a suspected/interacting drug. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR).Results: Of 27,370,413 total reports in VigiBase, we found 3,972 ARF reactions to gliflozins as suspected/interacting drugs in 3,751 patients and 231 nephrolithiasis reactions in 227 patients. Most cases were reported from American regions (3057; 81.49%), for patients of age group 45–64 years (1590; 59%). About 30% (1156) of the ARF reports were registered in 2018, most from spontaneous reporting, and from consumers followed by healthcare professionals (2,235; 61% and 1440; 38%, respectively). Canagliflozin was the most involved gliflozin in the ARF and nephrolithiasis cases (2,640; 67% and 109; 47%, respectively). The great majority of ARF and nephrolithiasis reports were serious (3,761; 95% and 182; 79%, respectively). Of the total ARF cases reported, 51 had fatal outcome, while 152 had not recovered/not resolved outcome. No fatal outcome was reported for nephrolithiasis. Disproportionality analysis in full database showed a PRR of 4.68 (95% CI 4.53–4.83) for all gliflozins–ARF and a PRR of 3.44 (95% CI 3.00–3.95) for all gliflozins–nephrolithiasis.Conclusion: Most of ARF reports associated with gliflozins were serious, with an important number of cases with fatal outcome. A drug safety signal was found between ARF narrow SMQ and gliflozins. Also, gliflozins were associated with an increase in the proportion of nephrolithiasis reports compared to other medications.

Diabetes mellitus (DM) is one of the leading causes of morbidity and mortality worldwide. DM patients with diabetic neuropathy (DN) usually present with distal pain, sensorimotor polyneuropathy, postural hypotension, or erectile dysfunction. They also may present with other nerve pathologies such as inflammatory neuropathies and carpal tunnel syndrome. We conducted a systematic review and meta-analysis to assess the benefits of using sodium–glucose co-transporter-2 inhibitors (SGLT2Is) to manage DN. An extensive systematic literature review was conducted to include all articles published up to 24 February 2022. All clinical studies included patients with DM and reported the outcomes of SGLT2I on diabetes-associated neuropathy. Six studies were identified for meta-analysis, including a total of 5312 diabetic patients. The average age of the included patients ranged from 41 to 74 years and 34–73 years in the SGLT2I treatment and control groups, respectively. SGLT2I moderately improved the manifestations of diabetic peripheral neuropathy events and nerve conduction velocity. Furthermore, the SGLT2I treatment group had a statistically significant higher mean heart-to-mediastinum ratio (MD 0.41; 95% 0.17, 0.64; p = 0.0006). However, the mean heart rates (MD −4.51; 95% −10.05, 1.04; p = 0.11) and wash out rates (MD 2.13; 95% −8.48, 12.75; p = 0.69) were not significantly different between the two groups. SGLT2Is could therefore be considered neuroprotective in patients with DN, possibly by considerably increasing the sensory and motor nerve conduction velocity, improving the clinical manifestations of DPN, and reducing sympathetic nervous system activity.Systematic Review Registration:http://www.crd.york.ac.uk/prospero/, identifier CRD42022312828

Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.

Nutritional and pharmacological therapies represent the basis for non-dialysis management of CKD patients. Both kinds of treatments have specific and unchangeable features and, in certain cases, they also have a synergic action. For instance, dietary sodium restriction enhances the anti-proteinuric and anti-hypertensive effects of RAAS inhibitors, low protein intake reduces insulin resistance and enhances responsiveness to epoetin therapy, and phosphate restriction cooperates with phosphate binders to reduce the net phosphate intake and its consequences on mineral metabolism. It can also be speculated that a reduction in either protein or salt intake can potentially amplify the anti-proteinuric and reno-protective effects of SGLT2 inhibitors. Therefore, the synergic use of nutritional therapy and medications optimizes CKD treatment. Quality of care management is improved and becomes more effective when compared to either treatment alone, with lower costs and fewer risks of unwanted side effects. This narrative review summarizes the established evidence of the synergistic action carried out by the combination of nutritional and pharmacological treatments, underlying how they are not alternative but complementary in CKD patient care.

Sodium-glucose cotransporter inhibitors (SGLT2i) play an increasingly important role in type 2 diabetes mellitus (T2DM) due to their significant cardiovascular benefits and renal protection in addition to their hypoglycemic effects. In recent years, the application of SGLT2i in patients with type 1 diabetes mellitus (T1DM) has attracted more and more attention. Studies have shown that SGLT2i improves glycemic control, reduces total daily insulin dose, decrease body weight in patients with T1DM, without increasing the risk of severe hypoglycemia. SGLT2i also reduces urinary protein levels, prevents atherosclerosis, and offers cardiorenal benefits in patients with T1DM. But simultaneously, they significantly increased risk of diabetic ketoacidosis (DKA), which leads to increased hospitalization and mortality. Hence SGLT2i is recommended to T1DM who are motivated, adhere to self-glucose monitoring, well-trained in identifying DKA, and closely followed to ensure the efficacy and safety.

Despite the significant impact of statin therapy, patients continue to face substantial residual cardiovascular risk. These risks are particularly prominent in patients with both type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We examine the effectiveness of a cardiometabolic clinic, embedded within a suburban cardiology private practice, in identifying and managing several of these multifaceted risks. We collated interventions for the first 100 patients with T2D and ASCVD who attended a minimum of two appointments at the clinic. Following an average of 2.4 clinic visits, 44 of 100 patients had undergone intensification of lipid-lowering therapy, with 16 initiated on PCSK9-directed therapies. This resulted in 85 of 100 patients achieving LDL-C levels below the 2022 ACC Expert Consensus Decision Pathway recommendations for intensification. Lipoprotein(a) was measured in 80 patients, revealing elevated levels in 22. At baseline, 18 and 32 patients were on glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), respectively. This increased to 80 and 66 patients on GLP1RA and SGLT2i, respectively, with 94 patients on either class and 52 patients on both. Figure 1 presents baseline and follow-up use of cardiometabolic therapies. The cardiometabolic clinic effectively identified and intensified management of several residual cardiovascular risks in patients with T2D and ASCVD. Extensive use of combination lipid-lowering therapies substantially addressed cholesterol-related risk, and initial experiences support the feasibility of high-volume implementation of GLP1RA and SGLT2i therapies in this population. [ABSTRACT FROM AUTHOR]

Arrhythmias are clinically prevalent with a high mortality rate. They impose a huge economic burden, thereby substantially affecting the quality of life. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) is a new type of hypoglycemic drug, which can regulate blood glucose level safely and effectively. Additionally, it reduces the occurrence and progression of heart failure and cardiovascular events significantly. Recently, studies have found that SGLT2i can alleviate the occurrence and progression of cardiac arrhythmias; however, the exact mechanism remains unclear. In this review, we aimed to discuss and summarize new literature on different modes in which SGLT2i ameliorates the occurrence and development of cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Aims: This three-year follow-up study aimed to elucidate whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) have any protection against diabetic neuropathy and nephropathy in patients with type 2 diabetes via reducing variability in glycemia and extraglycemic factors or their averages. Methods: Two type 2 diabetic cohorts of 40 and 73 patients treated with or without SGLT2i along with 60 control subjects were recruited. Two diabetic cohorts matched for HbA1c levels and oral hypoglycemic agents other than SGLT2is underwent glycemic control with or without SGLT2is more than two years. The urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) every 3 months and neuropathy outcome measures and mean Z-score of 8 neurophysiological tests were determined at the baseline and endpoint. Glycemic variability, evaluated by the coefficient of variation of monthly measured HbA1c levels and casual postprandial plasma glucose (CPPG), and coefficient of variation and average of extraglycemic parameters in diabetic cohorts were determined. Results: The glycemic variability and variability of some extraglycemic factors in SGLT2i cohort were smaller than those in non-SGLT2i cohort. However, only smaller coefficient of variation of HbA1c improved some neuropathy outcome measures, and ameliorated eGFR decline. SGLT2i improved the Z-score of neurophysiological tests. The optimized changes in the blood pressure, HDL-cholesterol and uric acid by SGLT2i led to neurological and renal protection. SGLT2i decreased the prevalence of nephropathy significantly and the prevalence of neuropathy insignificantly. Conclusion: Over 3 years period, SGLT2i significantly improved some neuropathy outcome measures, mean Z-score of 8 neurophysiological tests, and attenuated nephropathy in modestly controlled type 2 diabetes by reducing glycemic variability and mean nonglycemic factors of diabetic microvascular complication. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) has been unequivocally proven in randomized, controlled trials. However, real-world evidence assessing the implementation of SGLT2i in clinical practice and their benefit in HF outside of highly selected study populations is limited. Methods: Patients with HF and T2DM admitted to the cardiology ward of the Medical University of Vienna between 01/2014 and 04/2020 were included in the present analysis. All first-time prescriptions of SGLT2i were identified. The outcome of interest was cardiovascular mortality. The median follow-up time was 2.3 years. Results: Out of 812 patients with T2DM and HF (median age 70.4 [IQR 62.4–76.9] years; 70.3% males), 17.3% received an SGLT2i. The frequency of SGLT2i prescriptions significantly increased over the past 6 years (+ 36.6%, p < 0.001). In propensity score–adjusted pairwise analyses, SGLT2i treatment was inversely associated with long-term cardiovascular mortality in patients with HFrEF presenting with an adjusted HR of 0.33 (95%CI: 0.13–0.86; p = 0.024). Conclusion: Despite large outcome trials showing a cardiovascular benefit, SGLT2i remain underutilized in clinical practice in patients with T2DM and HF. National and European Medical Agency remuneration regulations would allow more patients at high risk to receive these cardiovascular protective drugs. Most importantly, an SGLT2i therapy was associated with a survival benefit in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter 2 inhibitors, also known as gliflozins, were developed as a novel class of anti-diabetic agents that promote glycosuria through the prevention of glucose reabsorption in the proximal tubule by sodium-glucose co-transporter 2. Beyond the regulation of glucose homeostasis, they resulted as being effective in different clinical trials in patients with heart failure, showing a strong cardio-renal protective effect in diabetic, but also in non-diabetic patients, which highlights the possible existence of other mechanisms through which gliflozins could be exerting their action. So far, different gliflozins have been approved for their therapeutic use in T2DM, heart failure, and diabetic kidney disease in different countries, all of them being diseases that have in common a deregulation of the inflammatory process associated with the pathology, which perpetuates and worsens the disease. This inflammatory deregulation has been observed in many other diseases, which led the scientific community to have a growing interest in the understanding of the biological processes that lead to or control inflammation deregulation in order to be able to identify potential therapeutic targets that could revert this situation and contribute to the amelioration of the disease. In this line, recent studies showed that gliflozins also act as an anti-inflammatory drug, and have been proposed as a useful strategy to treat other diseases linked to inflammation in addition to cardio-renal diseases, such as diabetes, obesity, atherosclerosis, or non-alcoholic fatty liver disease. In this work, we will review recent studies regarding the role of the main sodium-glucose co-transporter 2 inhibitors in the control of inflammation. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to highlight the evidence behind landmark trials involving these two novel drug classes in conjunction with a review of long-standing therapies used to improve cardiovascular (CV) outcomes among patients with peripheral artery disease (PAD) patients and type 2 diabetes mellitus (T2DM). Recent Findings: Recently, societal guideline recommendations have expanded the management of T2DM to incorporate therapies with CV risk factor modification. This is due to CV outcome trials (CVOT) uncovering advantageous cardioprotective effects of several novel therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Providers who manage high-risk patients with T2DM, such as those with concomitant PAD, are expected to incorporate these novel medical therapies into routine patient care. Summary: The body of evidence surrounding GLP-1 RA demonstrates a strong benefit in mitigating the innate heightened CV risk among patients with T2DM. Furthermore, SGLT2i not only have a favorable CV profile but also reduce the risk of HF hospitalizations and progression of renal disease. Patients with T2DM and PAD are known to be at a heightened risk for major adverse cardiac and lower extremity events, heart failure, and chronic kidney disease. As such, the use of novel therapies such as GLP-RA and SGLT2i should be strongly considered to minimize morbidity and mortality in this vulnerable population. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) have been shown to reduce the risk of worsening heart failure (HF) in subjects with HF and a reduced ejection fraction (HFrEF) in multiple clinical trials. The DAPACARD clinical trial was conducted to examine the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency, and myocardial contractile work in subjects with type 2 diabetes mellitus. As a complement to the clinical study, a mechanistic mathematical model of cardiorenal physiology was used to quantify the influence of established natriuretic/diuretic effects of SGLT2i on cardiac function (myocardial efficiency and global longitudinal strain). Virtual participants reflecting the participant‐level characteristics in the DAPACARD trial were produced by varying model parameters over physiologically plausible ranges. A second virtual population was generated by inducing a state of HFrEF in the DAPACARD virtual participants with type 2 diabetes mellitus for comparison. Cardiac responses to placebo and SGLT2i were simulated over 42 days. Cardiac hemodynamic improvements were predicted in DAPACARD‐HFrEF virtual participants but not in DAPACARD virtual participants. In particular, the natriuresis/diuresis induced by SGLT2i improved the global longitudinal strain and myocardial efficiency in DAPACARD‐HFrEF virtual participants within the first 14 days (change from baseline: global longitudinal strain, –0.95%; and myocardial efficiency, 0.34%), whereas the global longitudinal strain and myocardial efficiency in DAPACARD virtual participants were slightly worse (change from baseline: global longitudinal strain, 0.35%; and myocardial efficiency: –0.01%). The results of the DAPACARD virtual participants modeling were in line with the clinical data but do not preclude additional effects from other mechanisms of SGLT2i. [ABSTRACT FROM AUTHOR]

A major paradigm in nephrology states that the loss of filtration function over a long time is driven by a persistent hyperfiltration state of surviving nephrons. This hyperfiltration may derive from circulating immunological factors. However, some clue about the hemodynamic effects of these factors derives from the effects of so-called nephroprotective drugs. Thirty years after the introduction of Renin-Angiotensin-system inhibitors (RASi) into clinical practice, two new families of nephroprotective drugs have been identified: the sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the vasopressin receptor antagonists (VRA). Even though the molecular targets of the three-drug classes are very different, they share the reduction in the glomerular filtration rate (GFR) at the beginning of the therapy, which is usually considered an adverse effect. Therefore, we hypothesize that acute GFR decline is a prerequisite to obtaining nephroprotection with all these drugs. In this study, we reanalyze evidence that RASi, SGLT2i, and VRA reduce the eGFR at the onset of therapy. Afterward, we evaluate whether the extent of eGFR reduction correlates with their long-term efficacy. The results suggest that the extent of initial eGFR decline predicts the nephroprotective efficacy in the long run. Therefore, we propose that RASi, SGLT2i, and VRA delay kidney disease progression by controlling maladaptive glomerular hyperfiltration resulting from circulating immunological factors. Further studies are needed to verify their combined effects. [ABSTRACT FROM AUTHOR]

Aims: Sodium‐glucose cotransporter 2 (SGLT2) inhibitors have been shown to be an effective therapy in improving heart failure outcomes. We conducted a meta‐analysis of randomized controlled trials to evaluate the efficacy of SGLT2 inhibitors in heart failure patients with either a reduced or preserved ejection fraction. Methods and results: We searched MEDLINE and EMBASE for large (≥1000 patients) randomized controlled trials evaluating the effects of SGLT2 inhibitors compared with placebo in the setting of heart failure until September 2021. Our primary outcome was the composite of heart failure hospitalization and cardiovascular death, and secondary outcomes included all‐cause mortality and total heart failure hospitalizations. We pooled hazard ratios and risk ratios and evaluated risk of bias with the Cochrane Collaboration tool. Four randomized controlled trials (DAPA HF, EMPEROR‐Preserved, EMPEROR‐Reduced, and SOLOIST‐WHF) were included (n = 15 684); two of which evaluated patients with a reduced LVEF, one of which evaluated patients with a preserved LVEF, and one of which included both. Treatment with SGLT2 inhibitors resulted in a significant reduction in the composite of CV death and heart failure hospitalization (HR: 0.76, 95% CI: 0.70, 0.82, I2: 0%, P < 0.00001). This was consistent in sub‐groups of patients with LVEF ≤40% (n = 9199, HR: 0.74, 95% CI: 0.68, 0.81, I2: 0%) and LVEF >40% (n = 6482, HR: 0.78, 95% CI: 0.68, 0.89, I2: 0%, P‐for‐interaction: 0.57), as well as in sub‐groups of patients with and without diabetes mellitus at baseline (P‐for‐interaction: 0.81). SGLT2 inhibitors were associated with a significant reduction in cardiovascular death (HR: 0.87, 95% CI: 0.79, 0.97, I2: 0%, P < 0.00001) and total heart failure hospitalization (RR: 0.71, 95% CI: 0.67, 0.76, I2: 0%, P < 0.00001); although a potential trend towards reduced all‐cause mortality was noted with SGLT2 inhibitors, no statistically significant difference was observed (HR: 0.91, 95% CI: 0.83, 1.00, I2: 14%, P = 0.05). Conclusions: Sodium‐glucose cotransporter 2 inhibitors reduce cardiovascular death and heart failure hospitalization among patients with heart failure, regardless of LVEF status. [ABSTRACT FROM AUTHOR]

Yihai Liu,1,2,* Mingyue Wu,1,* Biao Xu,1 Lina Kang1 1Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lina Kang; Biao XuDepartment of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of ChinaEmail kanglina@njglyy.com; xubiao62@nju.edu.cnBackground: Recent clinical studies have revealed that sodium glucose co-transporter 2 inhibitors (SGLT2i) reduced cardiovascular events in type 2 diabetes. Here, we investigated whether empagliflozin, as a kind of SGLT2i, could alleviate atherosclerosis progression in non-diabetic mice.Methods: ApoE-/- mice were fed on a western diet for 12 weeks to induce atherosclerosis. The treatment group of mice was treated with drinking water containing empagliflozin (10mg/kg/day). On the 12th week, the whole aortas of each group were harvested. HE and Movat staining were performed for atherosclerotic lesion area and size. CD 68 and MCP-1 immunohistochemistry were used to evaluate inflammatory cell infiltration. Mouse serum lipid profiles (total cholesterol, triglyceride, low-density lipoprotein-C, and high-density lipoprotein-C), systemic inflammation level (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) and sympathetic activity (norepinephrine and neuropeptide Y) were measured by ELISA.Results: Empagliflozin could reduce the atherosclerotic lesion areas. Specifically, empagliflozin could significantly decreased inflammatory levels, RAAS and sympathetic activity in vivo. In vitro studies also showed that empagliflozin could inhibit IL-1β expression in oxLDL-treated macrophages by regulating NF-κB signaling.Conclusion: Empagliflozin could prevent atherosclerosis by repressing inflammation and sympathetic activity.Keywords: atherosclerosis, SGLT2i, empagliflozin, sympathetic activity, RAAS

Arrhythmias are clinically prevalent with a high mortality rate. They impose a huge economic burden, thereby substantially affecting the quality of life. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) is a new type of hypoglycemic drug, which can regulate blood glucose level safely and effectively. Additionally, it reduces the occurrence and progression of heart failure and cardiovascular events significantly. Recently, studies have found that SGLT2i can alleviate the occurrence and progression of cardiac arrhythmias; however, the exact mechanism remains unclear. In this review, we aimed to discuss and summarize new literature on different modes in which SGLT2i ameliorates the occurrence and development of cardiac arrhythmias.

AimsThis three-year follow-up study aimed to elucidate whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) have any protection against diabetic neuropathy and nephropathy in patients with type 2 diabetes via reducing variability in glycemia and extraglycemic factors or their averages.MethodsTwo type 2 diabetic cohorts of 40 and 73 patients treated with or without SGLT2i along with 60 control subjects were recruited. Two diabetic cohorts matched for HbA1c levels and oral hypoglycemic agents other than SGLT2is underwent glycemic control with or without SGLT2is more than two years. The urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) every 3 months and neuropathy outcome measures and mean Z-score of 8 neurophysiological tests were determined at the baseline and endpoint. Glycemic variability, evaluated by the coefficient of variation of monthly measured HbA1c levels and casual postprandial plasma glucose (CPPG), and coefficient of variation and average of extraglycemic parameters in diabetic cohorts were determined.ResultsThe glycemic variability and variability of some extraglycemic factors in SGLT2i cohort were smaller than those in non-SGLT2i cohort. However, only smaller coefficient of variation of HbA1c improved some neuropathy outcome measures, and ameliorated eGFR decline. SGLT2i improved the Z-score of neurophysiological tests. The optimized changes in the blood pressure, HDL-cholesterol and uric acid by SGLT2i led to neurological and renal protection. SGLT2i decreased the prevalence of nephropathy significantly and the prevalence of neuropathy insignificantly.ConclusionOver 3 years period, SGLT2i significantly improved some neuropathy outcome measures, mean Z-score of 8 neurophysiological tests, and attenuated nephropathy in modestly controlled type 2 diabetes by reducing glycemic variability and mean nonglycemic factors of diabetic microvascular complication.

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. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a complex clinical syndrome involving structural and/or functional abnormalities of the heart. Heart failure is often classified based on left ventricular ejection fraction, which serves as a predictor of mortality. The majority of the data supporting disease-modifying pharmacological therapies are from patients with reduced ejection fraction (less than 40%). However, with the recent results from the sodium glucose cotransporter-2 inhibitor trials, there is renewed interest in identifying potential beneficial pharmacological therapies. This review focuses on and includes pharmacological HF therapies across the spectrum of ejection fraction, providing an overview of the novel trials. We also examined the effects of the treatments on mortality, hospitalization, functional status, and biomarker levels to further investigate the interplay between ejection fraction and HF.

SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 μg/mL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 μM of empagliflozin, 1 μM canagliflozin, or 1 μM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 μg/mL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i: empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.

Introduction: To predict acute kidney injury (AKI) risk in patients with type 2 diabetes (T2D) prescribed sodium-glucose cotransporter two inhibitors (SGLT2i). Methods: Using a 5% random sample of Medicare claims data, we identified 17,694 patients who filled ≥1 prescriptions for canagliflozin, dapagliflozin and empagliflozin in 2013–2016. The cohort was split randomly and equally into training and testing sets. We measured 65 predictor candidates using claims data from the year prior to SGLT2i initiation. We then applied three machine learning models, including random forests (RF), elastic net and least absolute shrinkage and selection operator (LASSO) for risk prediction. Results: The incidence rate of AKI was 1.1% over a median 1.5 year follow up. Among three machine learning methods, RF produced the best prediction (C-statistic = 0.72), followed by LASSO and elastic net (both C-statistics = 0.69). Among individuals classified in the top 10% of the RF risk score (i.e., high risk group), the actual incidence rate of AKI was as high as 3.7%. In the logistic regression model including 14 important risk factors selected by LASSO, use of loop diuretics [adjusted odds ratio (95% confidence interval): 3.72 (2.44–5.76)] had the strongest association with AKI incidence. Disscusion: Our machine learning model efficiently identified patients at risk of AKI among Medicare beneficiaries with T2D undergoing SGLT2i treatment. [ABSTRACT FROM AUTHOR]

Lifetime diabetes risk is greater in women than in men. Women with diabetes mellitus (DM) have a greater prevalence of diabetic kidney disease (DKD) risk factors. The diagnosis of DM is often delayed in women, with poorer outcomes and with expected therapeutic goals missed. A systematic literature review following PRISMA guidelines was conducted in the PubMed gateway of the MEDLINE database and Clinicaltrials.gov. The purpose of our research was to establish the sex differences on renal outcomes in users of the new hypoglycemic drugs: sodium-glucose transport protein 2 inhibitors (SGLT-2i), dipeptidyl peptidase-IV Inhibitors (DPP-IVi) and glucagon-like peptide-1 inhibitors (GLP-1i). New hypoglycemic drugs represent promising tools in the treatment and prevention of severe complications of diabetes, cardiovascular diseases and chronic kidney disease. Even if renal outcomes are investigated in both randomized controlled trials and cardiovascular outcome trials, gender-based analysis is not always performed. Our systematic review demonstrated that the gap among sexes in DKD can be partially filled using new hypoglycemic drugs. Sexual dimorphism analysis could represent a keystone for the development of adequate gender-specific therapies. [ABSTRACT FROM AUTHOR]