SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells.

BACKGROUND: Sodium-glucose transporter 2 (SGLT2) inhibitors (iSGLT2) are approved medications for type 2 diabetes. Recent studies indicate that iSGLT2 inhibit the growth of some cancer cells. However, the mechanism(s) remains to be fully elucidated. METHODS: The SGLT2 levels were determined in normal colon CCD 841 CoN and, HCT 116, HT-29, SW480 and LoVo colorectal cancer (CRC) cell lines by quantitative real-time PCR and western blot. The effect of iSGLT2 canagliflozin on cell proliferation was examined using CCK-8, as its role on CRC cells metabolism and tumorigenesis has been evaluated by XF HS Seahorse Bioanalyzer and flow cytometric analyses. Transient gene silencing experiments and analysis of protein-protein interaction network were conducted to evaluate the SGLT2 molecular targets in CRC cells. RESULTS: Data showed that the treatment with iSGLT2 (50 µM) for 72 h induced cell cycle arrest (p < 0.001), impaired glucose and energetic metabolism (p < 0.001), promoted apoptotic cell death and ER stress flowing into autophagy (p < 0.001) in HCT 116 and HT-29 cells. These cellular events were accompanied by sirtuin 3 (SIRT3) upregulation (p < 0.01), as also supported by SIRT3 transient silencing experiments resulting in the attenuation of the effects of iSGLT2 on the cellular metabolic/energetic alterations and the induction of programmed cell death. The identification and validation of dipeptidyl peptidase 4 (DPP4) as potential common target of SGLT2 and SIRT3 were also assessed. CONCLUSIONS: These results deepened knowledge on the iSGLT2 contribution in limiting CRC tumorigenesis unveiling the SGLT2/SIRT3 axis in the cytotoxic mechanisms.

Documento de consenso sobre el uso de iSGLT2 en pacientes con enfermedad renal crónica y diabetes.

La enfermedad renal crónica (ERC) del paciente diabético es frecuentemente una consecuencia directa de la diabetes mellitus (DM) de larga evolución y se la conoce como nefropatía diabética. En México cerca del 50% de los pacientes en terapia sustitutiva de la función renal tienen ERC por DM, y este porcentaje podría aumentar en los próximos años. Nuevas opciones terapéuticas, combinadas con cambios en el estilo de vida, han mejorado el control de la glucemia y pueden contribuir sustancialmente a retrasar la aparición o la progresión a estadios avanzados de la ERC. Las sociedades científicas internacionales han elaborado guías clínicas para el diagnóstico y manejo de la nefropatía diabética, sin embargo, en algunos puntos estas recomendaciones no se adaptan a la realidad mexicana. Se presentan las conclusiones de un consenso realizado por especialistas mexicanos sobre diabetes y ERC, con especial énfasis en el uso de los inhibidores del cotransportador de sodio-glucosa.Chronic kidney disease (CKD) in the diabetic patient is mainly a consequence of long-term diabetes mellitus itself. In Mexico approximately 50% of patients on dialysis are diabetics and this will could increase in the coming years. New therapeutic options available, combined with lifestyle changes, have improved glycemic control and may contribute to delay the onset as well as the progression of CKD. International scientific societies have developed clinical guidelines for the diagnosis and management of CKD in diabetics, although in some points, these recommendations are not adapted to the Mexican reality. We hereby present the conclusions of the consensus reached by Mexican specialists on diabetic nephropathy.

Complications Secondary to the Use Of Sglt2 Inhibitors in Oncological Patients: A Series of 5 Cases.

Sodium-glucose cotransporter-2 (iSGLT2) inhibitors, which include dapagliflozin, canagliflozin and empagliflozin, are a class of drugs initially used in the oral treatment of diabetes, heart failure and renal failure. They target the reabsorption of glucose in the kidney. Although they bring benefit to patients with these conditions and in general produce few adverse effects, in some cases, iSGLT2 can cause serious adverse effects such as metabolic acidosis, and fungal or bacterial urinary infections. Oncology patients, who in general have a weak immune system and are usually treated with chemotherapy and/or immunotherapy, are more susceptible to this type of adverse events than other patients. For this reason, it is necessary to adequately select the patients eligible to receive this type of drug and evaluate the potential benefits for them. In this series of five cases, we present two cases of metabolic acidosis, two cases of bacterial urinary sepsis, and one case of fungal urinary sepsis that occurred in patients admitted to the Medical Oncology Department of the University Hospital of Salamanca in 2023. LEARNING POINTS: Adverse events associated with iSGLT2 can lead to serious complications in immunocompromised patients. There have been cases of prolonged admissions with high morbidity and mortality due to bacterial or fungal infections and metabolic acidosis, all of which are side effects derived from their use.In oncology patients, an adequate evaluation of the risk-benefit balance must be conducted before the introduction of new drugs.Studies should be conducted to assess the risk of serious adverse effects in oncology patients undergoing treatment with chemotherapy or immunotherapy.

Exploring the clinical utility of DPP-IV and SGLT2 inhibitors in papillary thyroid cancer: a literature review.

In the realm of clinical management, Papillary Thyroid Cancer (PTC) stands out as a prevalent thyroid malignancy, characterized by significant metabolic challenges, particularly in the context of carbohydrate metabolism. Recent studies have unveiled promising applications of Dipeptidyl Peptidase-IV (DPP-IV) and Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, which are conventionally employed in the treatment of type 2 diabetes mellitus (T2DM), as potential adjuncts in anticancer therapy. DPP-IV and SGLT2 inhibitors can be imply to counteract the Warburg effect in cancer, with a specific focus on PTC, owing to their potential metabolic advantages and their influence on the tumor microenvironment, achieved by imposing restrictions on glucose accessibility. Consequently, a comprehensive review has been undertaken, involving meticulous examination of the existing body of evidence pertaining to the utilization of DPP-IV and SGLT2 inhibitors in the context of PTC. The mechanisms of action inherent to these inhibitors have been thoroughly explored, drawing upon insights derived from preclinical investigations. Furthermore, this review initiates discussions concerning the implications for future research directions and the formulation of innovative therapeutic strategies for PTC. As the intricate interplay between carbohydrate metabolism, the Warburg effect, and cancer progression garners increasing attention, attaining a comprehensive understanding of the roles played by DPP-IV and SGLT2 inhibitors in PTC management may serve as the cornerstone for novel approaches aimed at enhancing patient care and broadening the spectrum of available therapeutic modalities.

Beyond Clinical Trials - The cost-saving associated with dapagliflozin use in portuguese hospital clinical practice.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. METHODS: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. RESULTS: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1 612 851.54 up to EUR 6 587 360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. CONCLUSIONS: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals.

Association of Sodium-Glucose Cotransporter-2 Inhibitors vs Dipeptidyl Peptidase-4 Inhibitors With Pneumonia, COVID-19, and Other Adverse Respiratory Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

OBJECTIVE: Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). METHODS: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis. RESULTS: Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i were associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i. CONCLUSION: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i.

Lupus nephropathy beyond immunosuppression: Searching for nephro and cardioprotection.

Renal involvement in systemic lupus erythematosus (SLE) represents one of the most frequent organ manifestations, often leading to end-stage kidney disease (ESKD). Several therapies have been tested in patients with lupus nephritis (LN) to prevent further organ damage. The effectiveness of immunosuppressive therapy as a treatment for LN is abundant, supported by multiple clinical trials that have shown its efficacy in preventing the development of chronic kidney disease (CKD). In addition to immunosuppressive therapy, several traditional and recent therapies aimed at nephroprotection in patients with proteinuric chronic kidney disease are gaining importance in the setting of LN. Thus, immunosuppressive therapy should be accompanied by nephro- and cardioprotective measures to control cardiovascular risk factors and proteinuria to ensure a better renal prognosis. Despite this, the literature on these specific measures is relatively scarce, with recommendations focused on the blockade of the renin-angiotensin-aldosterone system (RAAS). This review explores the pharmacological options available for cardiovascular and renal protection outside the usual treatment schemes.

Peri-colonoscopy Implications of Sodium-Glucose Cotransporter-2 Inhibitor Therapy: A Mini-review of Available Evidence.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of oral glucose-lowering agents commonly used for the treatment of type 2 diabetes. With increased use, there has been an increase in the incidence of the rare but life-threatening complication of euglycemic diabetic ketoacidosis. A common but underappreciated precipitant is colonoscopy. In this work, we outline the pathophysiology of the interaction between colonoscopy and SGLT2i use, the evidence regarding SGLT2i use in the periprocedural setting and Australian Diabetes Society guidelines.

SGLT2 Inhibition with Empagliflozin as a Possible Therapeutic Option for Postprandial Hypoglycemia After Bariatric Surgery.

PURPOSE: Since SGLT2 inhibitors may reduce postprandial hyperglycemia, this study aimed to evaluated whether empagliflozin might be useful in the treatment of postprandial hypoglycemia (PPH) postbariatric surgery (BS). PATIENTS AND METHODS: Fourteen patients who underwent BS, nine without type 2 diabetes and five with diabetes before surgery and in remission after surgery, were included. Seven of them presented symptoms of PPH (hypoglycemic group; HG) and seven were asymptomatic (nonhypoglycemic group (NHG)). A meal tolerance test was performed before and after administration of a daily dose of empagliflozin (EMPA) 25 mg for 3 days. Plasma glucose and serum insulin levels were measured. RESULTS: In HG, compared with NHG, in the basal test, the area under the curve (AUC) of plasma glucose levels (AUCgly) was smaller (158.3 ± 25.3 vs 276.6 ± 79.2 mg h dL-1; p = 0.001) while the AUC of insulin levels (AUCins) did not differ, leading to a higher AUCins/AUCgly ratio (0.79 ± 0.46 vs 0.38 ± 0.20; p = 0.055) and a lower HOMA-IR (0.92 ± 0.22 vs 1.75 ± 0.77; p = 0.030). The HG after EMPA, but not the NHG, showed significant increases in glycemia leading to greater AUCgly (158.0 ± 25.3 to 197.2 ± 51.6 mg h dL-1; p = 0.043) without significant changes in AUCins. HOMA-IR increased only in the HG (0.92 ± 0.20 vs 1.61 ± 0.30; p = 0.025) and, when both groups were analyzed together, both before and post EMPA, a significant correlation was found between HOMA-IR and AUCgly values (r = 0.594; p = 0.002). CONCLUSION: Our results suggest that empagliflozin increased glycemic levels in patients with PPH possibly through increases in hepatic glucose production.

Role of therapeutic inertia in glycemic control according to individualized objectives in a cohort of patients with type 2 diabetes. Results from CONCARDIA2.

BACKGROUND AND OBJECTIVE: Therapeutic inertia (TI) is the lack of initiation or intensification of treatment when indicated. It contributes to the fact that more than a third of people with type 2 diabetes mellitus (T2D) do not have adequate metabolic control. We set out to analyze the impact of TI during 4 years of follow-up in a cohort of T2D and its possible variables. MATERIALS AND METHODS: Prospective cohort study of a cohort of 297 TD2 patients. We considered TI when treatment was not modified during the 4 years, despite poor control. We contemplate uncontrolled those that did not meet their individualized HbA1c target. RESULTS: Uncontrolled patients: 87; age: 62.2 ±â€¯9.2; 58.7% men. We consider TI in 41.6% of the patients. Average HbA1c 8.22% in patients with treatment intensification of which 43.1% achieved their HbA1c goal, 29.8% were on monotherapy at the beginning, 29.8% double, 36.2% triple and 2,1% in quadruple therapy. There was more change in treatment in people with obesity (67.6 vs. 34.6%; P < 0.01) and the 6 of the study patients with cardiovascular events (P < 0.05). Metformin was part of the treatment in 97.1% of IT cases (vs. 76.6%; P < 0.01). Achievement of the HbA1c target was higher in patients receiving iSGLT2 (0 vs. 68.4%; P < 0.001). CONCLUSIONS: In 2 out of 5 uncontrolled T2D patients, the treatment was not changed; this was more evident in those patients treated with metformin. Patients with obesity and presence of cardiovascular events seem to protect against IT. Those who were on iSGLT2 have an advantage in meeting their HbA1c target.

Low Use of Guideline-recommended Cardiorenal Protective Antihyperglycemic Agents in Primary Care: A Cross-sectional Study of Adults With Type 2 Diabetes.

OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiorenal benefits independent of their glucose-lowering effects among persons living with type 2 diabetes mellitus (T2DM). In this study, we describe the proportion of persons with T2DM eligible to receive and currently receiving these agents based on their risk criteria for cardiorenal events. METHODS: This study was a cross-sectional analysis of primary care electronic medical records, in southern Alberta, of persons with T2DM who had at least 1 encounter with their primary care provider between December 31, 2018, to December 31, 2020. A descriptive and multivariate logistic regression analysis was conducted to examine clinical and demographic determinants of being prescribed one of the new treatments. RESULTS: Our study sample included 11,939 persons living with T2DM, among whom 66.3% had a cardiorenal indication for SGLT2i or GLP-1 RA use. In the secondary and primary prevention subsamples, 19.4% and 16.6% of persons were prescribed SGLT2i or GLP-1 RA, respectively, compared with 20.0% of those with no specific cardiorenal indication. Several person-level characteristics, such as age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.96 to 0.97), male sex (OR, 1.37; 95% CI, 1.21 to 1.55) and glycated hemoglobin (OR, 1.29; 95% CI, 1.24 to 1.34), were associated with being prescribed SGLT2i or GLP-1 RA. CONCLUSIONS: Low rates of SGLT2i or GLP-1 RA use and minimal differences between high-risk and no cardiorenal indication subsamples suggest the presence of barriers to prescribing these medications in a primary care setting. Action to highlight the indications for, and improve access to agents with, cardiorenal benefits will be required to achieve better outcomes for people with T2DM in primary care.

Sodium-Glucose Cotransporter-2 Inhibitor-associated Euglycemic Diabetic Ketoacidosis: Lessons From a Case Series of 4 Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Euglycemic diabetic ketoacidosis (DKA) is a potentially life-threatening adverse condition associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). This risk is further pronounced in the perioperative period. There is no consensus for when SGLT2i should be held preoperatively, and recommendations from various organizations have evolved from 1 day to 3 to 4 days in the latest American Diabetes Association guidelines. Further study of patients with perioperative euglycemic DKA is required to help clarify the optimal timing of preoperative discontinuation of SGLT2i agents. METHODS: In this retrospective, single-centre case series we examined 4 patients who developed postoperative euglycemic DKA after coronary artery bypass grafting, 3 of whom underwent semiurgent surgery. We characterized their clinical course, predisposing factors and treatment characteristics. RESULTS: The SGLT2i were held for 1 to 5 days preoperatively, with times since last dose before surgery being 54, 79, 80 and 151 hours. Surgery was semiurgent for 3 patients, and elective for 1 patient. Three patients were diagnosed with euglycemic DKA within 24 hours after surgery. The fourth patient developed euglycemic DKA on postoperative day 3 in the context of significant hypovolemia and exhibited potential signs of protracted SGLT2i action at 7 days since the last dose. CONCLUSIONS: The duration of SGLT2i action and risk for DKA is variable and complex. Providers should hold SGLT2i at least 3 days before elective major surgery, with potentially longer times in high-risk patients. Careful vigilance should be used for perioperative DKA development in all patients recently exposed to SGLT2i.

[Ketogenic diet as a trigger for diabetic euglycaemic ketoacidosis in a patient under treatment with iSGLT2]. / Dieta cetogénica como factor desencadenante de cetoacidosis diabética euglucémica en un paciente en tratamiento con iSGLT2.

Euglycaemic diabetic ketoacidosis is a possible adverse effect of selective sodium-glucose cotransporter inhibitors 2 (isGLT2) in patients with diabetes. However, the main scientific societies have recently recommended low or very low carbohydrate diets for the treatment of diabetes, relating the latter with the onset of ketosis. The combination of treatment with these drugs and following this type of diet can be dangerous. We present the case of a 64-year-old patient, suffering from LADA type diabetes, under usual treatment with intensive insulin therapy in 4 doses, who a few days after starting empagliflocin and a very low carbohydrate diet presented severe euglycaemic ketoacidotic decompensation.

[The heart and kidney in diabetes: Heart and kidney in diabetes]. / Corazón y riñón en la diabetes: efectos de los glucosúricos.

The diabetic kidney presents excess expression and activity of the SGLT2 transporter of the proximal tubule. This situation increases the renal reabsorption of Na and glucose and reduces their distal supply. In addition to the metabolic effects on the internal environment of this excess reabsorbed glucose, the renal tubule is subjected to glycosylated stress capable of locally activating both apoptosis and inflammasome. The result is a progressive loss of nephron units, activation of transition of mesangial epithelium and collagen deposition. Activation of insulin signalling by the MAP kinase pathway and resistance to the metabolic effects of insulin take place. This is simultaneously combined with afferent vasodilation due to hyperglycaemia, tubuloglomerular feedback inhibition due to reduced distal fluid supply, podocyte dedifferentiation and reduction in their number, the latter effects being due to insulin resistance. The result is self-feeding renal damage, with intraglomerular hyper-pressure, podocyte dedifferentiation, tubular apoptosis, and local and distant activation of inflammasome. All these effects are susceptible to be totally or partially corrected by inhibiting glucose transport via the SGLT transporters.

[Safety of SGLT2 inhibitors. A review of the adverse drug reactions registered in a national database]. / Seguridad de los iSGLT-2. Revisión de las reacciones adversas notificadas a nivel nacional.

OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26.05%) to empagliflozin, and 61 (19.61%) to canagliflozin. There was a ratio of 52.1% women to 47.9% men. The mean age was 62.07±12.17years. There were 167 (53.7%) notifications were classified as non-serious and 144 (46.3%) as serious. A total of 534 ADRs were notified, with the most common being urinary tract infections in 37 (6.9%) cases, diabetic ketoacidosis in 30 (5.6%), balanoposthitis in 24 (4.5%), ketoacidosis in 16 (3%), vulvovaginal candidiasis in 16 (3%), dizzy spells in 11 (2.1%), and 10 (1.9%) with dysuria, Candida balanitis, and vulvovaginal pruritus. As regards the outcomes of the 534 ADRs, 55.6% recovered with no sequelae, with 14% still recovering, 4.9% not recovered, fatal in 1.1%, and unknown in 24.3%. CONCLUSIONS: The majority of the ADRs notified are infections of the urogenital tract, ketoacidosis, and kidney damage. Although the majority of the former were not serious, the ketoacidosis and kidney damage were, leading to hospital admission and being life threatening in some patients. For these reasons, it is recommended that they are, prescribed with caution, the warnings published by the health authorities consulted, as well as notify any ADR that is suspected in this therapeutic group, in order to improve and provide us with further knowledge.

Clinical assessment and treatment of diabetes in patients with chronic kidney disease. / Evaluación clínica y tratamiento de la diabetes en pacientes con enfermedad renal crónica.

Diabetes mellitus type 2 is the main cause of chronic kidney disease. Patients with this disease have higher morbidity and mortality and risk of hypoglycaemia than those without this disease. In 2010, type 2 diabetes was the reason for starting renal replacement therapy in 24.7% of patients. The prevalence of microalbuminuria, proteinuria and a reduced glomerular filtration rate is 36%, 8% and 22%, respectively. The presence of albuminuria is a predictor of chronic kidney disease. Diabetic kidney disease, previously known as diabetic nephropathy, refers to kidney disease caused by diabetes. Renal hyperfiltration is a marker of intraglomerular hypertension and a risk factor for onset and progression. The new antidiabetic drugs, mainly dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter inhibitors and glucagon-like peptide-1 agonists, have been shown to prevent or slow the progression of kidney disease.

Enfermedad renal diabética: pilares en el tratamiento / Diabetic kidney disease: pillars in treatment

Introducción: La diabetes mellitus (DM) es una enfermedad crónica inflamatoria muy frecuente y por ende una de las emergencias sanitarias mundiales de más rápido crecimiento en las últimas décadas. Hay tres ejes que impactan en la progresión del compromiso renal del paciente diabético. El eje hemodinámico, metabólico e inflamatorio. Resaltamos la importancia del componente inflamatorio como actor protagónico en el desarrollo de la Enfermedad renal diabética (ERD). El manejo del paciente con ERD debe ser holístico, con tres objetivos claros: buen control metabólico, disminuir progresión de la enfermedad renal y disminuir los desenlaces cardiovasculares adversos. Actualmente además de las intervenciones no farmacológicas, el control de los factores de riesgo, el uso de los IECAS/ARA II hay nuevos pilares en el tratamiento de la ERD. Objetivos: El objetivo de esta comunicación es revisar los nuevos pilares en el manejo de la ERD. En la revisión bibliográfica que se hizo, encontramos que hay tres nuevos pilares en el tratamiento. Los inhibidores SGLT-2, los agonistas del receptor GLP-1 y por último finerenona, que es un antagonista selectivo no esteroideo del receptor mineralocorticoide (ARM), no es un antidiabético. Con estas nuevas terapias el manejo actual de estos pacientes ha cambiado considerablemente. Conclusión: Hay nuevos pilares en el tratamiento de la ERD. Los inhibidores SGLT-2, los Agonistas del receptor GLP-1 y el uso de ARM como finerenona, que nos brindan beneficios cardio­renales y que hacen que hoy en día el tratamiento de la ERD tenga un mejor panorama.

Introduction: Diabetes mellitus (DM) is a very common chronic inflammatory disease and finally one of the fastest-growing global health emergencies in recent decades. Three axes impact the progression of renal compromise in diabetic patients. The hemodynamic, metabolic, and inflammatory axis. We highlight the importance of the inflammatory component as a leading actor in developing Diabetic Kidney Disease (DKD). The management of the patient with CKD must be holistic, with three clear objectives: reasonable metabolic control, slowing the progression of kidney disease, and reducing adverse cardiovascular outcomes. Currently, in addition to non-pharmacological interventions, the control of risk factors, and the use of ACE inhibitors/ARA II, there are new pillars in the treatment of CKD. Objectives: The objective of this communication is to review the new pillars in the management of DKD. In the bibliographic review that was carried out, we found that there are three new pillars in the treatment. SGLT-2 inhibitors, GLP-1 receptor agonists, and finally finerenone, which is a selective non-steroidal antagonist of the mineralocorticoid receptor (MRA), not an antidiabetic. With these new therapies, the current management of these patients has changed considerably. Conclusion: There are new pillars in the treatment of DKD. The SGLT-2 inhibitors, the GLP-1 receptor agonists, and the use of MRAs such as finerenone provide us with cardio-renal benefits and which today make the treatment of CKD have a better outlook.

Documento de consenso sobre el uso de iSGLT2 en pacientes con enfermedad renal crónica y diabetes / Consesus document in the use of SGLT inhibitors in patients with diabetes and chronic kidney disease

Resumen La enfermedad renal crónica (ERC) del paciente diabético es frecuentemente una consecuencia directa de la diabetes mellitus (DM) de larga evolución y se la conoce como nefropatía diabética. En México cerca del 50% de los pacientes en terapia sustitutiva de la función renal tienen ERC por DM, y este porcentaje podría aumentar en los próximos años. Nuevas opciones terapéuticas, combinadas con cambios en el estilo de vida, han mejorado el control de la glucemia y pueden contribuir sustancialmente a retrasar la aparición o la progresión a estadios avanzados de la ERC. Las sociedades científicas internacionales han elaborado guías clínicas para el diagnóstico y manejo de la nefropatía diabética, sin embargo, en algunos puntos estas recomendaciones no se adaptan a la realidad mexicana. Se presentan las conclusiones de un consenso realizado por especialistas mexicanos sobre diabetes y ERC, con especial énfasis en el uso de los inhibidores del cotransportador de sodio-glucosa.

Abstract Chronic kidney disease (CKD) in the diabetic patient is mainly a consequence of long-term diabetes mellitus itself. In Mexico approximately 50% of patients on dialysis are diabetics and this will could increase in the coming years. New therapeutic options available, combined with lifestyle changes, have improved glycemic control and may contribute to delay the onset as well as the progression of CKD. International scientific societies have developed clinical guidelines for the diagnosis and management of CKD in diabetics, although in some points, these recommendations are not adapted to the Mexican reality. We hereby present the conclusions of the consensus reached by Mexican specialists on diabetic nephropathy.

Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus

Resumen Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Abstract Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.