Kidney outcomes with SGLT2 inhibitor vs. DPP4 inhibitor use in older adults with diabetes.

BACKGROUND AND HYPOTHESIS: While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. METHODS: Using a nationwide claims database, we studied 6 354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. RESULTS: Following propensity score matching, 6 354 individuals including 1 271 SGLT2 inhibitor users and 5 083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction < 0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a ≥ 20%, ≥ 30%, and ≥ 40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. CONCLUSIONS: Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged ≥ 60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

Safety of SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists in US veterans with and without chronic kidney disease: a population-based study.

Background: We examined the real-world comparative safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. other newer anti-glycemic medications (dipeptidyl peptidase-4 inhibitors [DPP4i], glucagon-like peptide-1 receptor agonists [GLP1a]) in patients with and without chronic kidney disease (CKD). Methods: Among US Veterans with diabetes receiving care from the Veterans Affairs (VA) healthcare system over 2004-19, we identified incident users of SGLT2i vs. DPP4i vs. GLP1a monotherapy. In analyses stratified by CKD status, defined by estimated glomerular filtration rate and albuminuria, we examined associations of SGLT2i vs. DPP4i vs. GLP1a use with risk of infection-related (primary outcome) and genitourinary infection hospitalizations (secondary outcome) using multivariable Cox models. Findings: Among 92,269 patients who met eligibility criteria, 52% did not have CKD, whereas 48% had CKD. In the overall and non-CKD cohorts, compared to DPP4i use, SGLT2i use was associated with lower infection-related hospitalization risk (HRs [95% CIs] 0.74 [0.67-0.81] and 0.77 [0.67, 0.88], respectively), whereas GLP1a use demonstrated comparable risk. However, in the CKD cohort SGLT2i and GLP1a use were each associated with lower risk (HRs [95% CIs] 0.70 [0.61, 0.81] and 0.91 [0.84, 0.99], respectively). Propensity score-matched analyses showed similar findings in the non-CKD and CKD cohorts. In the overall, non-CKD, and CKD cohorts, SGLT2i use was associated with lower genitourinary infection hospitalization risk whereas GLP1a use showed comparable risk vs. DPP4i use. Interpretation: In a national cohort of Veterans with diabetes, compared with DPP4i use, SGLT2i use was associated with lower infection-related and genitourinary infection hospitalization risk. Funding: VA Health Services Research and Development, USA.

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.

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.

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.

Supplementation with Highly Standardized Cranberry Extract Phytosome Achieved the Modulation of Urinary Tract Infection Episodes in Diabetic Postmenopausal Women Taking SGLT-2 Inhibitors: A RCT Study.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 ± 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: -0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: -4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies.

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on the endothelium. In this review, we summarize the current knowledge on the direct in vitro effects of SGLT2is on endothelial cells, as well as the systematic observations in preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and endothelial cell survival and proliferation. Both in vitro and in vivo studies suggest that SGLT2is share a class effect on attenuating reactive oxygen species (ROS) and on enhancing the NO bioavailability by increasing endothelial nitric oxide synthase activity and by reducing NO scavenging by ROS. Moreover, SGLT2is significantly suppress inflammation by preventing endothelial expression of adhesion receptors and pro-inflammatory chemokines in vivo, indicating another class effect for endothelial protection. However, in vitro studies have not consistently shown regulation of adhesion molecule expression by SGLT2is. While SGLT2is improve endothelial cell survival under cell death-inducing stimuli, their impact on angiogenesis remains uncertain. Further experimental studies are required to accurately determine the interplay among these mechanisms in various cardiovascular complications, including heart failure and acute myocardial infarction.

Real-Life Experience on the Effect of SGLT2 Inhibitors vs. Finerenone vs. Combination on Albuminuria in Chronic Kidney Disease.

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. RESULTS: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (-0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was -3.4 (8.8), -5.3(10.1), and -7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. CONCLUSIONS: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients.

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.

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.

The lower incidence of endometrial cancer after sodium-glucose cotransporter 2 inhibitors administration in type 2 diabetes mellitus population: a nationwide cohort study.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.

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.

Effects of newer anti-hyperglycemic agents on cardiovascular outcomes in older adults: Systematic review and meta-analysis.

AIM: To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups. METHODS: PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years). RESULTS: For SGLT-2is, five CVOTs (46,969 patients, 45-50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85-0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73-0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79-0.93]) with no difference in subgroups <65 or ≥65 years. For GLP-1RAs, nine CVOTs (n = 64,236, 34-75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83-0.95]), stroke (RR; 0.86 [CI, 0.76-0.97]) and ACM (RR; 0.90 [CI, 0.83-0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years. Four CVOTs (n = 33,063; 35-58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups. CONCLUSION: The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.

Magnesium Biology.

Magnesium (Mg2+) is essential for energy metabolism, muscle contraction, and neurotransmission. As part of the Mg-ATP complex, it is involved in over 600 enzymatic reactions. Serum Mg2+ levels are tightly regulated between 0.7 mmol/L and 1.1 mmol/L by interplay of intestinal absorption and renal excretion. In the small intestine, Mg2+ is absorbed paracellularly via claudin-2, and -12. In the colon, transcellular absorption of Mg2+ is facilitated by TRPM6/7 and CNNM4. In the kidney, the proximal tubule reabsorbs only 20% of the filtered Mg2+. The majority of the filtered Mg2+ is reabsorbed in the thick ascending limb (TAL), where the lumen-positive transepithelial voltage drives paracellular transport via claudin-16/-19. Fine-tuning of Mg2+ reabsorption is achieved in the distal convoluted tubule (DCT). Here, TRPM6/7 tetramers facilitate apical Mg2+ uptake, which is hormonally regulated by insulin and EGF. Basolateral Mg2+ extrusion is Na+ dependent and achieved by CNNM2 and/or SLC41A3. Hypomagnesemia (serum Mg2+ < 0.7 mmol/L) develops when intestinal and/or renal Mg2+ (re)absorption is disturbed. Common causes include alcoholism, type 2 diabetes mellitus, and the use of pharmacological drugs, such as proton-pump inhibitors (PPIs), calcineurin inhibitors (CNIs) and thiazide diuretics. Over the last decade, research on rare genetic and acquired Mg2+ disorders have identified Mg2+ channel and transporter activity, DCT length, mitochondrial function, and autoimmunity as mechanisms explaining hypomagnesemia. Classically, treatment of hypomagnesemia depended on oral or intravenous Mg2+ supplementation. Recently, prebiotic dietary fibers and SGLT2 inhibitors have been proposed as promising new therapeutic pathways to treat hypomagnesemia.

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.

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.

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.

Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation's role in cardiac fibrosis and evaluates emerging anti-diabetic medications' effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF.

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.