SGLT2 Research Articles

7490 Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 inhibitors; Switch Study in Real-World Setting

Abstract Disclosure: H. Choe: None. M. Kwak: None. J. Lee: None. Y. Choi: None. E. Hong: None. Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) represent two distinct pharmacological pathways in the management of type 2 diabetes, both aiming to improve glycemic control without risk of hypoglycemia. Metabolic implications and glycemic control associated with the interchange between SGLT2i and DPP-4i are scarce. This study aimed to evaluate the effect of switching between SGLT2i and DPP4i on various clinical parameters in Korean patients with type 2 diabetes. Methods: We conducted a retrospective cohort study at Hallym University Dongtan Sacred Heart Hospital, using clinical data warehouse. Baseline measurements and follow-up data at 3 months were collected for parameters including hemoglobin A1c (HbA1c), blood pressure, lipid profile, liver enzymes, renal function, and other metabolic markers. Results: Between 2015 and 2023, 104 participants switched from SGLT2 inhibitors to DPP4 inhibitors, while 321 switched in the opposite direction. Initially, those who switched from SGLT2 inhibitors to DPP4 inhibitors presented with lower baseline HbA1c levels (7.22 ± 0.73% versus 7.42 ± 0.76%, P = 0.017) and higher estimated glomerular filtration rates (eGFR) (95.2 ± 23.1 versus 85.9 ± 23.7 mL/min/1.73m², P = 0.001) compared to those who switched from DPP4 inhibitors to SGLT2 inhibitors. At three months of follow-up, the SGLT2 inhibitors to DPP4 inhibitors group exhibited a more significant reduction in HbA1c (adjusted β 0.22, 95% CI 0.03 to 0.40, P = 0.023), especially in patients with reduced eGFR (<60 mL/min/1.73 m²) (β 1.2, 95% CI 0.30 to 2.11, P = 0.013; P for interaction = 0.005). On the other hand, the DPP4 inhibitors to SGLT2 inhibitors group showed a greater decrease in fasting glucose levels (β -9.73, 95% CI -17.6 to -1.86, P = 0.016), along with more pronounced reductions in liver enzymes AST (β -4.15, 95% CI -6.49 to -1.81, P < 0.001) and ALT (β -6.42, 95% CI -9.58 to -3.27, P < 0.001), and a significant increase in hematocrit (β 3.31, 95% CI 2.36 to 4.26, P < 0.001) compared to the initial group. Conclusions: The study concludes that in Korean patients with type 2 diabetes, switching from SGLT2 inhibitors to DPP4 inhibitors is associated with a greater reduction in HbA1c, particularly in those with reduced renal function. Conversely, switching from DPP4 inhibitors to SGLT2 inhibitors results in more substantial improvements in fasting glucose and liver enzyme levels, suggesting differential benefits depending on the direction of the medication switch. Presentation: 6/3/2024

8707 Are We Adequately Prescribing Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) Or Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) In Patients With Type 2 Diabetes Mellitus (T2DM) And Established Atherosclerotic Cardiovascular Disease (ASCVD) Or Chronic Kidney Disease (CKD) In An Outpatient Setting: A Community Center Experience

Abstract Disclosure: R.K. Maan: None. A. Sawhney: None. A. Hayat: None. S. Kc: None. A. Madan: None. S. K c: None. L. Williams: None. A. Zweben: None. A. Rana: None. Introduction: The American Diabetes Association (ADA) recommends prescribing Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) or Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and established Atherosclerotic Cardiovascular Disease (ASCVD) or Chronic Kidney Disease (CKD) for its cardiovascular benefits. Methods: Our retrospective study analyzed data from 511 T2DM patients who visited the outpatient clinic between 7/1/22 to 6/30/23. Using Microsoft Excel, we assessed adherence to ADA guidelines by collecting data for SGLT2i, GLP-1 RA and statin prescriptions, urine microalbumin creatinine ratio measurements, and appropriate management of albuminuria. The study also investigated patients on dipeptidyl peptidase-4 inhibitors (DPP-4i) who were eligible for SGLT2i or GLP-1 RA. Results: Out of the 511 patients, 478 were eligible for SGLT2i or GLP-1 RA, and only 60% were prescribed these medications. Out of 479 patients eligible for statin prescription, only 85% were on it. Albuminuria was appropriately managed in 76% of eligible patients with Angiotensin-Converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs). Additionally, 8 out of 11 patients on DPP-4i were eligible for SGLT2i or GLP-1 RA. Conclusion: We concluded that 60% of the patients eligible for SGLT2i or GLP-1 RA were prescribed the medication in our outpatient settings. The barriers identified were issues with insurance prior authorization and knowledge gaps. We aim to improve adherence to guidelines through multifaceted education strategies combined with audits and feedback.

Prescription of quadruple therapy in heart failure with reduced ejection fraction during hospitalization

BackgroundHospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition.MethodsWe conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors.ResultsFrom September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function.ConclusionsThe low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients.

Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA

IntroductionThis study aimed to assess recent trends in the US use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) in people with type 2 diabetes...

Diuretics and risk of major adverse limb events in patients with type-2 diabetes: An observational retrospective study

AimIn patients with type-2 diabetes mellitus (T2DM), sodium-glucose co-transporter 2 inhibitors are suspected to increase the risk of amputation. “Traditional” diuretics may increase major adverse limb events (MALEs), but the evidence is weak. We studied the association between common diuretics (i.e. thiazides, loop- and potassium-sparing diuretics) and MALEs/amputations in patients with T2DM. MethodsConsecutive T2DM patients without cardiovascular history referred to our center for cardiovascular check-ups were retrospectively studied. Follow-up data on MALEs were collected. We used Cox models to assess the association between diuretics and MALEs, or amputation alone. A propensity score with inverse probability of diuretic treatment weighting (IPTW) analysis was performed. ResultsWe studied 1309 patients, (59.5 ± 10.7 years, 51 % females) with diabetes duration of 9.1 ± 8.5 years, among whom 402 (30 %) were taking diuretics. During a follow-up of 3.8 ± 1.64 years, 121 (9.1 %) had MALEs, including 19 (1.4 %) amputations. Death occurred in 111 patients and the proportion of death was significantly different between groups: patients with diuretics n = 49, 44.1% vs patients without diuretics n = 62, 55.9 %, P = 0.001. Diuretics, in multivariable analysis, were associated with MALEs (aHR[95 %CI] 1.96[1.32;2.91] P = 0.001), even after adjustment on propensity score (aHR 1.66[1.08;2.56] P = 0.02) and IPTW analysis (aHR 1.76[1.67;1.84] P < 0.0001). This risk was particularly increased in case of an abnormal ankle-brachial index (aHR 2.29[1.32;3.96], P = 0.003) at baseline. Looking at diuretic classes separately, the adjusted risk was increased with loop diuretics (aHR 2.56[1.16;5.64] P = 0.020), thiazides (aHR 2.21[1.37;3.57] P = 0.001) or potassium sparing diuretics (aHR 2.56[1.16;5.64] P = 0.020). ConclusionDiuretic treatment weighting may be associated with increased risk of MALEs. We identified several markers of increased risk of limb events where the use of diuretics should be considered with caution.

SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists Effects on Kidney and Clinical Outcomes in Veterans with Type 2 Diabetes.

The primary aim compared kidney endpoints between patients with type 2 diabetes (T2D) 36 months after initiation on a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a GLP-1 receptor agonist (GLP-1RA). Secondary aims compared estimated glomerular filtration rate (eGFR), hemoglobin A1c (HbA1c), weight, and urine albumin-to-creatinine ratio (UACR) changes. We conducted a retrospective cohort study of propensity score matched veterans with T2D, baseline eGFR>20mL/min/1.73m2, and initiated on a SGLT2i vs GLP-1RA between 4/1/2009-9/1/2020. Cox proportional hazard models were constructed to evaluate effectiveness between both groups on composite endpoint (decline of >=40% in eGFR from baseline, ESRD event, and all-cause mortality) and its components adjusting for baseline characteristics. Spline models were constructed to evaluate eGFR change and linear mixed effects models were constructed to evaluate changes in HbA1c, weight, and UACR. We used an intent-to-treat (ITT) approach as our main analysis followed by a per-protocol (PP) approach excluding veterans who discontinued or switched therapy during the study period. A total of 29,146 propensity score matched veterans were included in SGLT2i and GLP-1RA groups (14,573 per group). In the ITT and PP analyses, veterans initiated on SGLT2i had a 35% (HR=0.65; 95% CI: 0.62, 0.68) and 34% (HR=0.66; 95% CI: 0.62, 0.69) reduction in the hazard of experiencing the composite endpoint compared to veterans initiated on GLP-1RA adjusting for baseline characteristics, respectively. Between 6-36 months, we found an improved chronic eGFR slope with SGLT2i compared to GLP-1RA in both ITT and PP analyses; +1.19 mL/min/1.73 m2 (95% CI: 0.93, 1.45) and +1.29 mL/min/1.73m2 (95% CI: 1.01, 1.57), respectively. The annual difference in chronic eGFR slope in both ITT and PP analyses were +0.97 mL/min/1.73m2/year (95% CI: 0.82, 1.11) and +1.08 mL/min/1.73m2/year (95% CI: 0.92, 1.25). Improved HbA1c, weight loss and UACR were reported for both groups. In this real-world study, veterans with T2D initiated on SGLT2i were associated with reduced hazard of experiencing mortality, worsening eGFR, or developing ESRD and improved glycemic, metabolic, and renal endpoints compared to GLP-1RA use.

The role of coronary microcirculation in heart failure with preserved ejection fraction: An unceasing odyssey.

Heart failure with preserved ejection fraction (HFpEF) represents an entity with complex pathophysiologic pathways, among which coronary microvascular dysfunction (CMD) is believed to be an important orchestrator. Research in the field of CMD has highlighted impaired vasoreactivity, capillary rarefaction, and inflammation as potential mediators of its development. CMD can be diagnosed via several noninvasive methods including transthoracic echocardiography, cardiac magnetic resonance, and positron emission tomography. Moreover, invasive methods such as coronary flow reserve and index of microcirculatory resistance are commonly employed in the assessment of CMD. As far as the association between CMD and HFpEF is concerned, numerous studies have highlighted the coexistence of CMD in the majority of HFpEF patients. Additionally, patients affected by both conditions may be facing an adverse prognosis. Finally, there is limited evidence suggesting a beneficial effect of renin-angiotensin-aldosterone system blockers, ranolazine, and sodium-glucose cotransporter-2 inhibitors in CMD, with further evidence being awaited regarding the impact of other pharmacotherapies such as anti-inflammatory agents.

Short term sodium glucose transport protein 2 inhibitors are associated with post contrast acute kidney injury in patients with diabetes

Although sodium–glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48–72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0–20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.

Dapagliflozin's Role in Heart Failure: An Overview of Clinical Trial Evidence.

Heart failure (HF) has become a global health threat, necessitating the development of novel treatment options to address this crisis. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as dapagliflozin, may offer significant advantages in the treatment of HF, particularly in patients with reduced ejection fraction (HFrEF). This systematic review combines the findings from clinical studies to evaluate the safety and effectiveness of dapagliflozin in HF patients. The study results demonstrate dapagliflozin's consistent improvements in reducing adverse cardiovascular events, including cardiovascular death rates across different HF phenotypes. Mechanistically, dapagliflozin exerts diuretic and hemodynamic effects, along with its actions on myocardial metabolism, ion transporters, fibrosis, adipokines, and vascular function, which collectively contribute to its cardioprotective effects. This overview emphasizes dapagliflozin's key role in HF management, positioning it as one of the central pillars of the HF treatment regimen. Further studies are essential to fully understand dapagliflozin's long-term effectiveness, safety, and integration into routine clinical practice, ultimately improving patient outcomes in HF.

Hypoglycemic drugs, circulating inflammatory proteins, and gallbladder diseases: A mediation mendelian randomization study

BackgroundThe relationship of hypoglycemic drugs, inflammatory proteins and gallbladder diseases remain unknown. MethodsFour hypoglycemic drugs were selected as exposure: glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin. The outcome were two gallbladder diseases: cholecystitis and cholelithiasis. Mendelian Randomization (MR) was employed to determine the association between hypoglycemic drugs and gallbladder diseases. ResultsDPP-4i and SGLT-2i had no effect on cholecystitis and cholelithiasis. However, a causal relationship was found between inhibition of ETFDH gene, a target of metformin expressed in cultured fibroblasts, and cholelithiasis (OR: 0.84, 95 %CI: (0.72,0.97), p = 0.021), as well as between GLP1R expression in the brain caudate basal ganglia and cholecystitis (OR: 1.29, 95 %CI: (1.11,1.49), p = 0.001). The effect of ETFDH inhibition on cholelithiasis through Interleukin-10 receptor subunit beta (IL-10RB) levels and Neurotrophin-3 (NT-3) levels, with a mediated proportion of 8 % and 8 %, respectively. ConclusionMetformin plays a protective role in cholelithiasis, while GLP-1RA have a harmful effect on the risk of cholecystitis. Metformin may reduce the risk of cholelithiasis by modulating the levels of Neurotrophin-3 (NT-3) and Interleukin-10 receptor subunit beta (IL-10RB). Further clinical and mechanistic studies are required to confirm these findings.

The use of sodium-glucose cotransporter type 2 inhibitors for the treatment of chronic heart failure in cancer patients receiving cardiotoxic chemotherapy. Preliminary results.

Background. Chronic heart failure (CHF) is one of the most serious and late manifestations of cardiotoxicity during treatment with antitumor drugs in cancer patients. As of today, only 2 groups of drugs have proven significant cardioprotective effects in this category of patients: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and beta-blockers (BABs). Only recently has data emerged on the successful use of sodium-glucose cotransporter type 2 inhibitors (SGLT-2) in patients with CHF on anthracycline therapy.Aim. To evaluate the role of SGLT-2 inhibitors in the complex treatment of CHF in cancer patients receiving cardiotoxic chemotherapy.Methods. A prospective observational open study, including 60 patients with verified CHF who received cardiotoxic chemotherapy and dual cardioprotective therapy: ACEIs/ARBs + BABs (control group); and 56 patients who receive similar therapy with the addition of Dapagliflozin 10 mg 1 time in the morning (study group). The results were monitored after 6 months using laboratory and instrumental research methods, as well as additional control methods. Results. Troponin T, N-terminal prohormone of brain natriuretic peptide (NTproBNP) and left ventricular longitudinal strain (GLS) levels were compared in 47 patients who had completed all follow-up studies at 6 months. It was noted that the dynamics of troponin in both groups did not differ significantly (p0.753 and p0.260, respectively), and the level of NTproBNP significantly decreased in the study group by 7.8% compared to the control group (p0.006). Comparable data were obtained for GLS (a decrease in the study group by 6.5% in relative values) compared to the control group (p0.008)). 22 (46.8%) patients had CHF before the start of chemotherapy, and in 25 (53.2%) CHF arose during antitumor drug therapy. There were 17 (16%) deaths, but there were no deaths from heart failureinbothgroups.Conclusion. We believe that a decrease in the marker of heart failure and a less pronounced impairment of the longitudinal deformation of the left ventricle with the addition of SGLT-2 inhibitors to the basic therapy of CHF in cancer patients receiving cardiotoxic chemotherapy can slow down the progression of CHF.

Comprehensive Benefits of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure With Reduced Ejection Fraction: A Literature Review.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for type 2 diabetes, have emerged as a promising treatment for heart failure with reduced ejection fraction (HFrEF). They show significant cardiovascular benefits, including reduced cardiovascular mortality and heart failure hospitalizations. This review consolidates knowledge on the efficacy of SGLT2 inhibitors in HFrEF, focusing on their mechanisms of action, clinical benefits, and patient outcomes. To consolidate existing knowledge on the efficacy of SGLT2 inhibitors in reducing cardiovascular mortality in HFrEF, with an emphasis on pathophysiology, clinical benefits, and patient outcomes, major medical databases such as PubMed, Scopus, and Web of Science were reviewed, prioritizing research published from 2020 to 2024. Key studies and clinical trials, including DAPA-HF and EMPEROR-Reduced, were analyzed to understand the impacts of SGLT2 inhibitors on HFrEF management. The review highlights the multifaceted mechanisms by which SGLT2 inhibitors exert their cardiovascular benefits, including osmotic diuresis, natriuresis, improved myocardial energetics, and anti-inflammatory and antifibrotic effects. Clinical trials have consistently demonstrated significant reductions in cardiovascular mortality and hospitalizations among HFrEF patients treated with SGLT2 inhibitors. These benefits are observed across diverse demographic and clinical subgroups, indicating their broad applicability in clinical practice. SGLT2 inhibitors significantly advance HFrEF management, reducing cardiovascular mortality and hospitalizations. However, gaps remain in long-term outcomes, early diagnostic indicators, and mechanisms of action. Future research should address these gaps and explore personalized medicine to optimize treatment. Integrating SGLT2 inhibitors into standard HFrEF management guidelines, supported by updated policies and educational initiatives for healthcare providers, will be crucial to maximize their therapeutic potential and improve patient outcomes.

Advances in SGLT2 Inhibitors for Type 2 Diabetes Management

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a significant class of medications for the management of type 2 diabetes mellitus, offering improved glycemic control and cardiovascular benefits. This review focuses on the development of various SGLT2 inhibitors, highlighting their chemical structures, pharmacological properties, and therapeutic potential. Methods: A comprehensive literature review was conducted, summarizing the synthesis and biological evaluation of multiple SGLT2 inhibitors, including novel compounds derived from C-aryl glucoside scaffolds, C-glucosides, and 5α-carba-β-D-glucopyranose derivatives. Studies utilized various techniques, such as click chemistry, Friedel-Crafts alkylation, and pharmacokinetic assessments, to evaluate the efficacy and selectivity of these inhibitors. Results: Several promising compounds were identified, including compound 1 (GCC5694A) with an IC50 of 0.460 nM against SGLT2 and strong selectivity for SGLT1, and compound 26, which exhibited an IC50 of 4.47 nM, surpassing dapagliflozin. Novel derivatives, such as compound 22 (IC50 = 47 nM) and compound 27, demonstrated significant inhibitory effects and selectivity profiles. Pharmacokinetic studies revealed compounds like compound 28 had enhanced half-lives compared to established drugs like sergliflozin. Additionally, compounds such as the nitric oxide-releasing dapagliflozin derivative exhibited dual anti-diabetic and anti-thrombotic properties. Conclusion: The ongoing development of SGLT2 inhibitors demonstrates substantial advancements in therapeutic options for type 2 diabetes. The structural modifications and novel compounds explored in this review highlight the potential for improved efficacy and safety profiles, suggesting that these new agents could play a vital role in diabetes management and warrant further clinical investigation.

Assessing 1-year sodium-glucose co-transporter-2 inhibitor tolerance in older adults.

Evidence concerning tolerability of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older adults is limited due to under-representation in clinical trials. Our study aimed to determine the extent to which SGLT2 inhibitor intolerance increases with age and explore additional factors associated with intolerance. This retrospective observational study included patients in the Veterans Health Administration who initiated an SGLT2 inhibitor between 1 January 2013 and 31 December 2021. One-year discontinuation served as a proxy for intolerance. Relative risk (RR) for 1-year discontinuation was contrasted across age groups using log-binomial regression to adjust for confounding. Of 232 495 patients who initiated an SGLT2 inhibitor, 60 582 (26.1%) discontinued within one year. A difference was observed across age groups, <65, 65-74, 75-84 and ≥85years, where 25.8%, 25.3%, 28.5% and 34.9% of patients discontinued, respectively (P < .001). After adjustment for confounding factors, patients 75-84 and ≥85years were at 8% (RR = 1.08; 95% CI: 1.05, 1.10) and 21% increased risk (RR = 1.21; 95% CI: 1.15, 1.26) for discontinuation, respectively, relative to patients <65years. Additional risk factors were identified: female (RR = 1.41; 95% CI: 1.37, 1.45), estimated glomerular filtration rate stage 4 (RR = 1.49; 95% CI: 1.39, 1.60), underweight (RR = 1.15; 95% CI: 1.03, 1.29), urinary tract infection history (RR = 1.25; 95% CI: 1.21, 1.30) and yeast infection history (RR = 1.39; 95% CI: 1.27, 1.51). No clinically meaningful differences in SGLT2 inhibitor intolerance were observed in patients up to 84years. Our findings support having closer follow-up when initiating in patients 85years and older.

A Highly Sensitive Inclusion Complex Based Spectrofluorimetric Method for the Determination of Certain Sodium Glucose Cotransporter-2 Inhibitors: Greenness Assessment and Application to Different Biological Fluids.

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (β-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE).

Uric Acid and SGLT2 Inhibition With Empagliflozin in HeartFailure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF. This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF). Hyperuricemia (SUA >5.7mg/dL for women, >7.0mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95%CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95%CI: 1.08-1.86]; P= 0.01). SUA was reduced early (after 4weeks vs placebo-0.99 ± 0.03mg/dL; P< 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95%CI: 0.51-0.76]; P< 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95%CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07). Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.

Identification of functional heterogeneity of immune cells and tubular-immune cellular interplay action in diabetic kidney disease.

Renal inflammation plays key roles in the pathogenesis of diabetic kidney disease (DKD). Immune cell infiltration is the main pathological feature in the progression of DKD. Sodium glucose cotransporter 2 inhibitor (SGLT2i) were reported to have antiinflammatory effects on DKD. While the heterogeneity and molecular basis of the pathogenesis and treatment with SGLT2i in DKD remains poorly understood. To address this question, we performed a single-cell transcriptomics data analysis and cell cross-talk analysis based on the database (GSE181382). The single-cell transcriptome analysis findings were validated using multiplex immunostaining. A total of 58760 cells are categorized into 25 distinct cell types. A subset of macrophages with anti-inflammatory potential was identified. We found that Ccl3+ (S100a8/a9 high) macrophages with anti-inflammatory and antimicrobial in the pathogenesis of DKD decreased and reversed the dapagliflozin treatment. Besides, dapagliflozin treatment enhanced the accumulation of Pck1+ macrophage, characterized by gluconeogenesis signaling pathway. Cell-cross talk analysis showed the GRN/SORT1 pair and CD74 related signaling pathways were enriched in the interactions between tubular epithelial cells and immune cells. Our study depicts the heterogeneity of macrophages and clarifies a new possible explanation of dapagliflozin treatment, showing the metabolism shifts toward gluconeogenesis in macrophages, fueling the anti-inflammatory function of M2 macrophages, highlighting the new molecular features and signaling pathways and potential therapeutic targets, which has provided an important reference for the study of immune-related mechanisms in the progression of the disease.

A Long-Term Retrospective Real-World Evidence to Understand the Pattern of Insulin Prescription in Patients with Type 2 Diabetes Mellitus: Evaluating the Role of Insulin Initiation

Abstract Aims and Objective: To evaluate the prescription pattern of insulin and oral antidiabetic drugs (OADs) and the trend of glycemic control in people with diabetes (PwD) with type 2 diabetes mellitus attending a tertiary care center in India. Materials and Methods: This retrospective, cross-sectional observational study included clinic records of 647 PwD collected at three different time points (2011, 2015, and 2019). Population characteristics, patterns of glycemic parameters, and trends of antidiabetic medication were analyzed. Results: PwD population was similar in terms of anthropometric and clinical variables. Dysglycemia was observably higher in the 2015 population (mean HbA1C = 8.37 ± 1.8%) compared with the 2011 population (6.4 ± 0.4%) and stabilized in the 2019 population (8.35 ± 1.9%) compared with the 2015 population. This correlated with the trend of increase in basal and bolus insulin prescriptions as more subjects were initiated on insulin to address the higher dysglycemia in 2015 than in 2011 and were later titrated in 2019. The proportion of subjects with uncontrolled diabetes increased marginally in 2015 (50.9%) compared with 2011 (45.6%) and decreased significantly in 2019 (34.1%) compared with 2015. This correlated with the additive increases of premix insulin, sodium-glucose transport protein 2 inhibitors (SGLT2i), and dipeptidyl peptidase 4 inhibitors (DPP4i) prescriptions. Conclusion: We observed a judicious usage of insulin prescriptions correlating with the higher need for PwD to be initiated with basal insulin to counter the increasing trend of dysglycemia, followed by more premix insulin prescriptions to address stabilized dysglycemia. Optimal diabetes control can be partly attributed to dysglycemia stabilization by insulin initiation and usage of newer OADs, such as SGLT2i and DPP4i.

Protocolo terapéutico de la diabetes mellitus tipo 2 con nefropatía

The protocol describes the therapeutic management of patients with type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), a frequent complication in 20%–40% of individuals with DM2. Treatment is based on blood pressure control (target<130/80mmHg); angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) are recommended. For glycemic control, the glycosylated hemoglobin (HbA1c) level sought is individualized for each patient, but is generally below 7%, adjusting the medication according to the patient's estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT-2i) inhibitors and glucagon-like peptide-1 agonists (GLP-1a) are recommended for their renal and cardiovascular benefits. In addition, patients with CKD and DM2 should be treated with statins to reduce cardiovascular risk, avoiding drugs that increase the risk of hypoglycemia. Individualized treatment and frequent monitoring are essential, especially in patients with decreased eGFR and persistent albuminuria.

Comprehensive insights into diabetic nephropathy: pathophysiology, clinical features, and emerging treatments

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease globally, affecting 20–50% of diabetic patients. DN is characterized by albuminuria, retinopathy, and progressive reduction in glomerular filtration rate. The pathophysiology involves chronic hyperglycemia, protein glycosylation, mesangial matrix deposition, glomerular hemodynamic alterations, cytokine release, and renin-angiotensin-aldosterone system activation, leading to kidney damage. Differences in DN mechanisms between type 1 and type 2 diabetes are influenced by additional factors such as aging, obesity, and dyslipidemia. Prevention strategies focus on lifestyle modifications and regular screening. Pharmacological management includes tight glycemic control, blood pressure regulation, renin-angiotensin-aldosterone system blockade, and novel agents like sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Emerging therapies targeting inflammatory pathways and innovative medications offer promising avenues for future research. Comprehensive management integrating early detection and advanced pharmacological interventions is crucial to mitigating DN progression and improving patient outcomes.