SGLT2 Research Articles

The role of SGLT1 in atrial fibrillation and its relationship with endothelial-mesenchymal transition.

Atrial fibrillation (AF) is a prevalent arrhythmia closely associated with atrial fibrosis, posing significant challenges to cardiovascular health. Recent studies have identified the sodium-glucose co-transporter 1 (SGLT1) as a potential key player in the pathophysiology of heart diseases, particularly in the context of AF and atrial fibrosis. This review aims to synthesize current knowledge regarding the mechanisms by which SGLT1 influences the development of AF and atrial fibrosis, with a specific focus on its relationship with endothelial-mesenchymal transition (EMT). By analyzing the latest research findings, this paper discusses how SGLT1 may modulate structural and functional changes in the atria, thereby enhancing our understanding of the underlying mechanisms driving AF.

Comprehensive treatment with dapagliflozin in elderly chronic kidney disease patients: Clinical efficacy and impact on body composition.

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is widely used for treating heart failure and chronic kidney disease (CKD). While its renoprotective effects are well established, concerns remain regarding its impact on muscle mass and function, especially in elderly patients. To assess the effects of dapagliflozin on renal function, body composition, and muscle strength in elderly CKD patients. Twelve elderly CKD patients (75.6±1.4years) were treated with dapagliflozin for 12months. Body composition, serum parameters, and muscle function were evaluated at baseline, 6months, and 12months. Measurements included changes in eGFR, liver function, HbA1c, and muscle strength. Dapagliflozin treatment stabilized eGFR without significant improvement, but proteinuria was notably reduced in most patients, indicating a positive renal effect. AST and ALT levels showed significant reduction after 12months, suggesting improved liver function. No significant changes were observed in body weight, BMI, or muscle mass. Muscle function, as measured by the 5-sit-to-stand test, improved significantly, while grip strength remained stable. No serious adverse events were reported. Dapagliflozin is a safe and effective treatment for CKD in elderly patients, demonstrating renal protection and improved liver function without adversely affecting muscle mass or strength. The study supports the use of dapagliflozin as part of a comprehensive approach, combining pharmacotherapy, lifestyle modification, and exercise to optimize patient outcomes in CKD management.

Dapagliflozin for the treatment of heart failure with reduced ejection fraction in Brazil: a cost-effectiveness analysis.

Heart failure, a complex clinical syndrome with high morbidity and mortality, has become a significant burden on public health. Recently, a new class of antidiabetic agents-the sodium-glucose cotransporter 2 (SGLT2) inhibitors-was associated with a significant reduction on mortality and hospitalization in HF with reduced ejection fraction (HFrEF) when added to standard pharmacological treatment. Considering the lack of data on its cost-effectiveness, the present study aims to estimate the incremental cost-effectiveness ratio of add-on dapagliflozin treatment for HFrEF from the Brazilian public healthcare system perspective. We built a Markov model to estimate the clinical outcomes and costs of 1,000 hypothetical subjects with established HFrEF in a lifetime horizon. The model inputs were based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial and local data. The main outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained. Deterministic and probabilistic sensitivity analyses, as well as scenario analyses, were performed. The addition of dapagliflozin to standard care treatment in 1,000 HFrEF patients yielded an expected value of 366.99 additional QALYs at an incremental cost of US$ 1,517,878.49, resulting in an ICER of US$ 4,136.08 per QALY gained, being a cost-effective strategy considering the Brazilian official cost-effectiveness threshold (US$ 8,000/QALY). In probabilistic sensitivity analyses, 96.60% of the simulations were also cost-effective. In the scenario analyses, results were similar for individuals with and without diabetes. Dapagliflozin is likely to be cost-effective when added to standard HFrEF therapy in Brazil. This study was supported by the National Institute of Science and Technology for Health Technology Assessment (Instituto de Avaliação de Tecnologias em Saúde-IATS).

Dapagliflozin alleviated seizures and cognition impairment in pilocarpine induced status epilepticus via suppressing microglia-mediated neuroinflammation and oxidative stress.

Status epilepticus (SE) is a neurological emergency with prolonged seizures leading to chronic epilepsy, cognitive impairment, and neuronal damage. Microglial activation, subsequent neuroinflammation and oxidative stress contribute to SE-induced neuronal injury. Single-cell sequencing has delineated the pro-inflammatory microenvironment in epileptic lesions, characterized by widespread microglial activation. Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), has shown potential in modulating neuroinflammatory responses. This study aimed to investigate the effects of Dapagliflozin on seizure and cognitive impairment by alleviating microglia-mediated neuroinflammation, oxidative stress. Single-Cell Transcriptomic Analysis were used to reveal SLC5A2 cellular heterogeneity and subtype-specific signatures of Temporal lobe Epilepsy. Male C57BL/6 mice were administered pilocarpine. Dapagliflozin were injected immediately after the termination of SE and at 24-hour intervals after SE until sacrifice. The latency and seizure score were recorded. Morris water maze were used to evaluate cognitive function of mouse. The neuroinflammation cell model was induced by lipopolysaccharide(LPS) in BV2 cell. Immunofluorescent staining, immunohistochemistry, flow cytometry, western blot, RT-qPCR, ELISA etc were used to examine the activation of microglia, evaluate neuroinflammation and oxidative stress. The expression of SLC5A2 is up-regulated in microglia of epileptic patients. Administration of Dapagliflozin significantly reduced seizure activity and improved cognitive performance in SE mouse. Dapagliflozin reduced microglial activation, as indicated by downregulation of CD86, iNOS expression and increased CD206, Arg-1 level. Dapagliflozin decreased oxidative stress, as evidenced by reduced levels of malondialdehyde (MDA), reactive oxygen species (ROS), increased superoxide dismutase (SOD) and Glutathione (GSH) activity. In addition, Dapagliflozin treatment can rescured the neuronal damage and suppressed the release of inflammatory cytokines such as IL-6, IL-18 and IL-1β. Our findings suggest that Dapagliflozin exerts neuroprotective effects by modulating microglia-mediated neuroinflammation and oxidative stress. The inhibition of SGLT2 may represent a novel therapeutic strategy for the treatment of SE and associated cognitive impairments.

Treating chronic kidney disease in Danish primary care: results from the observational ATLAS study

ObjectivesTo describe the clinical characteristics, comorbidity, and medical treatment in a primary care population with chronic kidney disease (CKD). Additionally, to investigate how primary care physicians (PCPs) diagnose, manage and treat impaired kidney function, including uptake of cardio-renoprotective renin–angiotensin–aldosterone system inhibitors (RAASis) and sodium glucose co-transporter 2 inhibitors (SGLT2is).DesignAn observational study of CKD prevalence, treatment patterns and comorbidities in primary care based on patient record data combined with a questionnaire on diagnosis, management and treatment of impaired kidney function in a real-world, primary care setting.SettingIn all 128 primary care clinics in Denmark of 211 randomly invited and a quetionnaire completed by 125/128 participating PCPs.MethodsA computerized selection identified 12 random individuals with CKD per clinic with ≥ 2 measurements of eGFR < 60 mL/min/1.73 m2 or UACR > 30 mg/g within two years (N = 1 497). Pre-specified data collected from individual electronic health records included demographics, clinical variables, comorbidities, and relevant prescribed medications.ResultsOf the CKD study population (N = 1 497), 80% had hypertension, 32% diabetes (DM), 13% heart failure (HF), 59% no DM/HF. ACEis/ARBs were prescribed to 65%, statins to 56%, SGTL2is to 14%, and MRAs to 8% of all individuals. Treatment patterns differed between individuals with varying comorbidities, e.g., ACEis/ARBs usage was higher in DM (76%) or HF (74%) vs. no DM/HF (58%), as was statin usage (76% in DM vs. 45% in no DM/HF). SGTL2i usage in no DM/HF was low. Most PCPs identified CKD using eGFR < 60 mL/min/1.73 m2 (62%) or UACR > 30 mg/g (58%) and 62% reported initiating treatment to retard kidney function decline.ConclusionsDespite good PCP awareness and wish to use relevant guidelines, a gap exists in implementation of cardio-renoprotective treatment, especially in individuals without DM/HF. This offers an opportunity for clear recommendations to PCPs to optimize early cardio-renal protection in individuals with CKD.

Clinically approved representative small-molecule drugs for cardiopathy therapy.

The application of therapeutic agents for cardiopathy has brought about significant advancements in the treatment of cardiovascular diseases. The intervention of small-molecule drugs has led to substantial reductions in morbidity and mortality rates, along with decreased utilization of healthcare resources. However, current treatment modalities do not exhibit uniform efficacy across all patients, and the emergence of drug resistance poses a significant challenge to further therapeutic efforts. Additionally, chronic administration of these drugs can result in toxicities, adding complexity to long-term management. This review focuses on the application of clinically approved small-molecule drugs for the treatment of cardiopathy, covering major classes such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, β-blockers, and sodium-glucose co-transporter 2 inhibitors. The review provides an in-depth analysis of their synthetic routes, mechanisms of action, and roles in cardiopathy treatment. It also offers perspectives on future directions in the development of next-generation cardioprotective agents, aiming to optimize therapeutic strategies for cardiovascular disease management.

Canagliflozin reverses doxorubicin-induced cardiotoxicity via restoration of autophagic homeostasis

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been reported as successful for preventing doxorubicin (DOX) -induced cardiotoxicity (DIC), but the underlying mechanisms are elusive. This study aimed to determine whether canagliflozin, an SGLT2i, protects against DIC by regulation of autophagic flux in cardiomyocytes through a mechanism independent of SGLT2. The differentially expressed autophagy-related genes (ARGs) in DIC were analyzed. Neonatal rat cardiomyocytes (NRCMs), H9C2 rat cardiomyocytes or C57BL/6 mice were treated with canagliflozin or vehicle. The effects on cellular apoptosis and autophagy were investigated using qRT-PCR, western blotting and immunofluorescence. Additionally, cardiac function, myocardial fibrosis, and apoptosis of cardiomyocytes were also assessed in mice. The potential molecular targets of canagliflozin were identified through molecular docking analysis. A total of 26 differentially expressed ARGs were identified. Canagliflozin significantly activated autophagic flux and inhibited apoptosis of cardiomyocytes in both DOX-treated H9C2 rat cardiomyocytes and NRCMs. In a murine model of DIC, canagliflozin improved cardiac dysfunction by suppressing cardiac remodeling, fibrosis, and apoptosis. Moreover, canagliflozin promoted autophagy by enhancing SIRT1 levels and inhibiting the PI3K/Akt/mTOR signaling pathway. Immunofluorescence assays revealed that canagliflozin promoted the translocation of LC3 from the nucleus to the cytoplasm. Molecular docking analysis confirmed that canagliflozin has high affinity for targets associated with DIC. These findings suggest that canagliflozin protects cardiomyocytes from DOX-induced cell death by activating SIRT1, inhibiting the PI3K/Akt/mTOR pathway, and enhancing autophagic flux.

Predictors of Use of Individual Insulin and GLP-1 RA Products Versus Fixed Ratio Insulin/GLP-1 RA Combinations in Medicare Beneficiaries.

Background: In 2022, federal law capped insulin product costs at $35 per month for Medicare prescription drug plan recipients. However, this law did not address the high costs of other antihyperglycemic medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with an average copay of $120 per month. Under the law, fixed-ratio insulin/GLP-1RA combination products are classified as "insulin products," making these effective medications more accessible to patients who might otherwise be unable to afford them. Patients may not be aware of the potential financial benefits of combination products, highlighting the need to identify those using them to better educate both patients and providers. Objectives: The primary objective was to identify predictors of use for the insulin/GLP-1RA combinations. The secondary objective was to determine if there was a difference in medication cost to patients between individual and combination product users and determine cost savings potential of switching. Design: This was a retrospective, observational cohort analysis. Setting: Prescription fill data were examined for antihyperglycemic medications filled between January 1, 2022, and December 31, 2022. Prescriptions were filled within one regional division of a large community-based pharmacy chain, encompassing 71 pharmacies within Kansas, Nebraska, and Missouri. Methods: This retrospective observational cohort analysis examined prescription fill data for antihyperglycemic medications for the calendar year 2022 across one regional division of a large community-based pharmacy chain. Included patients 65 years of age or older with a Medicare prescription drug plan, using any basal insulin and any GLP-1RA, including combinations, as well as metformin, with ≥ 80% proportion of days covered. Demographics, usage predictors, and cost differences were compared between patients using individual products and those using insulin/GLP-1RA combination products. Results: A total of 138 patients were analyzed. The use of insulin/GLP-1RA combination products was associated with increased likelihood of using sodium-glucose cotransporter-2 inhibitors (P = 0.022). Median annual out-of-pocket spending was significantly different between groups (P < 0.001), with most combination users paying more than $1,000 less per year than individual product users. Conclusion: Insulin/GLP-1RA combination products represent a cost-effective alternative to individual antidiabetic pharmacotherapy agents.

American Society for Gastrointestinal Endoscopy position statement on periendoscopic management of patients on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.

American Society for Gastrointestinal Endoscopy position statement on periendoscopic management of patients on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.

Randomized trial to assess worsening renal function by adding dapagliflozin for acute decompensated heart failure.

Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has been shown to reduce cardiovascular mortality among patients with chronic heart failure. We aimed to evaluate the impact on a worsening renal function (WRF) by adding DAPA as compared to standard decongestive therapy with loop diuretics alone. We enrolled 114 consecutive acute decompensated heart failure (ADHF) patients with a left ventricular ejection fraction (LVEF) of less than 50%. The patients were prospectively randomized to be assigned either to DAPA group who received DAPA at a dose of 10mg once daily within 24h after admission or conventional therapy group (CON group) who received loop diuretics alone. All patients were adjusted by increasing or decreasing the loop diuretic by 10mg to maintain a 1-2mL/kg/h urine output. The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥0.3mg/dL from baseline. The median age of the patients was 77 [interquartile range (IQR): 64, 85] years, 35% were female and the median LVEF was 33 [IQR: 28, 38] %. There was no significant difference in the incidence of WRF between the two groups (16.1%, n=9 vs. 12.1%, n=7, P value=0.54). The total dose of loop diuretics through day 7 was lower in the DAPA group than CON group (184±79.5mg vs. 214±66.5mg, P value=0.03). This randomized prospective trial revealed the addition of DAPA within 24h after admission reduced the diuretic dose without WRF.

Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: a systematic review and network meta-analysis of randomized controlled trials

Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: a systematic review and network meta-analysis of randomized controlled trials

Heart failure and microvascular dysfunction: an in-depth review of mechanisms, diagnostic strategies, and innovative therapies

Microvascular dysfunction (MVD) is increasingly recognized as a critical contributor to the pathogenesis of heart failure (HF), particularly in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Coronary microvascular dysfunction (CMD) significantly impacts HFpEF by reducing coronary flow reserve and myocardial perfusion reserve, leading to adverse outcomes such as myocardial ischemia, diastolic dysfunction, and increased risk of major cardiovascular events, including atrial fibrillation. In HFrEF, microvascular impairment is linked to heightened oxidative stress, reduced nitric oxide production, and activation of the renin-angiotensin-aldosterone system, further driving disease progression and contributing to poor prognosis. Advancements in diagnostic techniques, such as positron emission tomography, cardiac magnetic resonance imaging, and biomarker analysis, improve our ability to assess CMD in heart failure patients, enabling earlier diagnosis and risk stratification. Emerging therapies, including sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, and endothelial-targeted interventions, enhance microvascular function and improve patient outcomes. The role of personalized medicine is becoming increasingly important, as individualized therapeutic approaches tailored to patient-specific microvascular abnormalities are essential for optimizing treatment effectiveness. This review underscores the pivotal role of MVD in HF. It highlights the urgent need for innovative therapeutic strategies and diagnostic tools to address this complex condition and improve clinical outcomes for HF patients.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) for pediatric kidney disease: the future is near

Sodium glucose co-transporter 2 inhibitors (SGLT2i) for pediatric kidney disease: the future is near

Prognostic significance of NT-proBNP levels in patients treated with empagliflozin.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been added to the mainstay of treatment for chronic heart failure. Recent studies suggest that empagliflozin may also reverse cardiac remodeling in heart failure by reducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. In our study, we wanted to show the decrease in NT-proBNP levels, which is an indicator of poor prognosis in heart failure, and to see if there was a decrease in the rate of renal progression in patients with HF after empagliflozin use. Patients with type 2 diabetes mellitus and heart failure using empagliflozin were selected from the system and 456 patients were found. Patients were divided into two groups: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The patients were divided into two groups according to their NT-proBNP levels at the beginning of the drug and on the 90th day. The laboratory data were analyzed at the time of drug initiation and at day 90. There was a statistically significant difference between baseline and day 90 HbA1C and NT-proBNP levels (p < 0.001), (p < 0.001). NT-proBNP and creatinine levels at baseline and day 90 were significantly higher in patients with HFrEF than in those with HFpEF (p < 0.001). According to the multivariate analysis, patients with HFrEF were 11.42 times more likely to have an NT-proBNP change above 300 pg/mL than patients with HFpEF (OR: 11.42, p = 0.028). In our study, a significant reduction in NT-proBNP and HbA1C levels was observed, while renal function was preserved.

Cardiovascular Outcomes in Patients with Complex Type 2 Diabetes Mellitus Treated with the Dual SGLT Inhibitor Sotagliflozin: A Meta-analysis.

Scientific publications have shown sodium-glucose co-transporter-2 (SGLT2) inhibitors to have several beneficial effects in patients with complex type 2 diabetes mellitus (T2DM). However, sodium-glucose co-transporter-1 (SGLT-1) inhibitor is still under investigation in clinical trials. Recently, a dual inhibitor of sodium-glucose co-transporter (SGLT1/2), sotagliflozin, has been approved for use in patients with T2DM. In this analysis, we aimed to systematically compare the cardiovascular outcomes in patients with complex T2DM who were treated with the newly approved dual (SGLT 1 and 2) inhibitor sotagliflozin. Electronic databases, including Embase, MEDLINE, http://www. gov , Web of Science, Google Scholar, the Cochrane database, and reference lists of relevant publications, were searched for publications comparing the novel SGLT1/2 inhibitor versus placebo for the treatment of patients with complex T2DM. The primary endpoint, including total number of deaths from cardiovascular causes, hospitalization for heart failure, and urgent visits for heart failure, death from cardiovascular causes, cardiac mortality, hospitalization for heart failure, non-fatal myocardial infarction, and total number of cardiac events, were considered as the endpoints in this analysis. The RevMan software version 5.4 was used to carry out the statistical analysis. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data following analysis. A total of 13,054 participants enrolled between 2017 and 2020 were included in this analysis, with 6734 participants assigned to sotagliflozin and 6320 assigned to placebo. The results of this analysis showed that the primary endpoint was significantly in favor of sotagliflozin with (RR: 0.73, 95% CI 0.67-0.80; P = 0.00001). Hospitalization for heart failure (RR: 0.67, 95% CI 0.60-0.75; P = 0.00001) and the total number of cardiac events (RR: 0.73, 95% CI 0.67-0.79; P = 0.00001) were also significantly lower with sotagliflozin when compared to placebo in these patients with complex T2DM. However, the risk for cardiovascular mortality and non-fatal myocardial infarction were not significantly different with (RR: 0.91, 95% CI 0.76-1.09; P = 0.31) and (RR: 0.92, 95% CI 0.27-3.12; P = 0.89), respectively. Cardiovascular outcomes, including the total number of adverse cardiac events and hospitalization for heart failure, were significantly reduced with the newly approved SGLT1/2 inhibitor sotagliflozin apparently showing its cardiovascular efficacy in patients with complex T2DM. Future trials with larger sample sizes and a longer follow-up time could possibly confirm this hypothesis.

Diabetes mellitus, vaginal microbiome and sexual function: Outcomes in postmenopausal women.

Diabetes mellitus is a chronic disease and a public health challenge worldwide, associated with numerous complications, including genitourinary infections and sexual dysfunction in women, particularly in menopause. The vaginal microbiome, which comprises beneficial and pathogenic bacteria, their genomes, and the surrounding environment, plays a crucial role in maintaining genitourinary health. Chronic hyperglycemia disrupts immune functions, exacerbates oxidative stress, and alters the vaginal microbiome, increasing the risk of genitourinary infections. Recent advances in microbial analysis, including 16S rRNA sequencing, have provided insights into the complex composition of the vaginal microbiome and its dysbiosis in diabetes mellitus. Some glucose-lowering drugs, such as sodium-glucose cotransporter 2 inhibitors, may increase the risk of genitourinary infections. Additionally, psychological distress, hormonal imbalances, and diabetes-related genitourinary symptoms contribute to sexual dysfunction in diabetic women. Healthcare for diabetic women requires a multidisciplinary approach, including not only glycemic control but also vaginal and sexual health assessment. A holistic approach is essential to advance personalized strategies, including medications and psychological support.

Sodium-Glucose Co-Transporter 2 Inhibitors and Severe Urinary Tract Infections: Real-World Meta-Analysis of Cohort Studies.

There is limited knowledge about severe urinary tract infections associated with SGLT2i, despite this being the basis for the Food and Drug Administration (FDA) warning. We aim to provide real-world evidence to clarify this relationship further. A literature review was performed in PubMed and Embase for cohort studies published up to August 2024 using PICO-consistent terms. Cohort studies in English involving new users of SGLT2i that compare SGLT2i with glucagon-like receptor agonists (GLP-1RA), DPP4i, and other glucose-lowering medications and report severe urinary tract infection (UTI). The random-effect model determined the odds ratio (OR) and 95% confidence interval (CI) for severe UTI. Subgroup analysis and meta-regression were used to identify sources of heterogeneity. In 11 cohort studies involving 679 617 individuals with type 2 diabetes mellitus and a median age of 64 (interquartile range [IQR] = 56-72) and 42% (IQR = 39%-51%) females, it was found that the use of SGLT2i was associated with a reduced risk of severe UTI compared with both composite glucose-lowering medications (OR = 0.73, 95% CI = 0.60-0.88) and DPP4i (OR = 0.48, 95% CI = 0.43-0.54). There was no significant difference in the risk compared with GLP-1RA (OR = 0.94, 95% CI = 0.78-1.14). The lack of increased risk for severe UTI reassures physicians when assessing benefit-risk to continue SGLT2i after a severe UTI. This may enhance patient adherence and improve diabetes management. Furthermore, our findings show no significant risk increase in chronic kidney disease (CKD) patients who would benefit significantly from SGLT2i. SGLT2i does not appear to pose a greater risk of severe UTI than other oral glucose-lowering medications. This contributes to the existing literature on UTI, accounting for the event's severity. However, more data are needed to assess the potential association between SGLT2i and life-threatening UTI events.

Chronic kidney disease.

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal - a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin-angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment.

Comparative effectiveness of insulin glargine, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in veterans with type 2 diabetes.

To compare the risk of all-cause death and cardiovascular events in new users of insulin glargine, glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR). We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP-1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023. Inverse probability weighted Cox regression models were used for treatment comparisons on all-cause deaths and cardiovascular events in the entire cohort and above subgroups. There were 20 788 cardiovascular events/414 414 person-years and 15 268 all-cause deaths/446 458 person-years. Insulin glargine had a higher hazard of all-cause death compared to GLP-1RA (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.48-1.67) or SGLT2i (HR 1.55, 95% CI 1.48-1.61) in the entire cohort and across subgroups, especially in those with HbA1C levels <9.0%. Results were similar for secondary outcomes. Compared to GLP-1RA, SGLT2i had similar risk of all-cause death (HR 1.03, 95% CI 0.97-1.10) but higher hazard of cardiovascular events (HR 1.13, 95% CI 1.08-1.19). Across subgroups, GLP-1RA and SGLT2i had generally similar effects, with SGLT2i showing a slightly higher risk in some cases. Insulin glargine might be deleterious particularly in those with HbA1C <9.0%. There was no clear evidence for prioritization of SGLT2i versus GLP-1RA across subgroups.

International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Insulin and Adjunctive Treatments in Children and Adolescents with Diabetes.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the principles of intensive insulin regimens, including more intensive forms of multiple daily injections with new-generation faster-acting and ultra-long-acting insulins; a summary of adjunctive medications used alongside insulin treatment that includes details on pramlintide, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and sodium-glucose cotransporter inhibitors; and key considerations with regard to access to insulin and affordability to ensure that all persons with diabetes who need insulin can obtain it without financial hardship.