Progress of pharmacotherapy for heart failure / 中国临床药理学与治疗学

Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.

Dapagliflozin review : More than an anti-diabetic drug

@#Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. DM is a significant health care concern. Worldwide, the prevalence is increasing at an alarming rate despite using different classes of anti-hyperglycemic agents. Although several treatment options reduce hyperglycemia, only half the patients achieve desirable glycemic targets. Newer treatments that significantly reduce hyperglycemia with novel mechanism of action and acceptable safety profiles are warranted to reduce complications associated with type 2 DM. Sodium-glucose cotransporter-2 inhibitors are anti-hyperglycemic agents with unique mechanism of action that lower blood glucose level independent of insulin. Recent findings on efficacy and safety establish their role in the treatment of DM. Sodium-glucose cotransporter-2 inhibitors may be an option in type 2 DM patients not willing or not ready to start insulin, those requiring additional glucose lowering and in those with acceptable risk factor profiles. Dapagliflozin (Farxiga) can be used at any stage of type 2 DM as a mono-therapy or in combination with other oral hypoglycemic agents and insulin. This review highlights the efficacy and safety of dapagliflozin as an anti-hyperglycemic agent and its use in co-morbid conditions like chronic kidney disease and cardiovascular diseases

Cetoacidosis diabética euglucémica asociada al uso de inhibidores del cotransportador de sodio-glucosa 2

RESUMEN Mujer de 48 años con antecedentes de diabetes mellitus tipo 2 tratada con empaglifozina acudió a consulta después de 8 horas de dolor abdominal, náuseas, vómitos y falta de aliento. Tras el examen físico, la paciente estaba alerta, álgica, pálida, con mucosas secas, taquipneica, taquicárdica y con dolor abdominal difuso sin signos de irritación peritoneal. Los resultados de su laboratorio mostraron una glucemia sérica de 115 mg/dL (70-100 mg/dL), gasometría arterial con acidosis metabólica con anión gap elevado 20 mmol/L. El análisis de orina reportó cetonuria (cuerpos cetónicos 150) y la HbA1C fue 12,4% (4,8%-6%). Se descartó una causa quirúrgica de dolor abdominal y finalmente fue diagnosticada con cetoacidosis diabética euglucémica secundaria al uso de Inhibidores del cotransportador de sodio-glucosa 2.

ABSTRACT A 48-year-old woman with a history of type 2 diabetes mellitus treated with empaglifozine came to consultation after 8 hours of abdominal pain, nausea, vomiting, and shortness of breath. After the physical examination, the patient was alert, allergic, pale, with dry mucosa, tachypnea, tachycardia, and with diffuse abdominal pain without signs of peritoneal irritation. The results of his laboratory showed a serum glucose of 115 mg/dL (70-100 mg/dL), arterial blood gasometry with metabolic acidosis with an elevated gap anion of 20 mmol/L. Urine analysis reported ketonuria (150 ketone bodies) and HbA1C was 12.4% (4.8% -6%). A surgical cause of abdominal pain was ruled out and she was finally diagnosed with euglycemic diabetic ketoacidosis secondary to the use of sodium-glucose cotransporter inhibitors 2.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

Analysis of 2 cases of diabetic ketoacidosis / 中华内分泌代谢杂志

Diabetic ketoacidosis ( DKA ) is one of the common endocrine emergencies. With the development and applications of new drugs, the inducing causes of DKA become more and more complicated. We as clinicians should quickly and accurately evaluute the severity of DKA, and administrate reasonable rehydration and hypoglycemic treatment. What we should do better is searching the causes of DKA and help patients reasonably avoid its occurrence. In this article, two cases from clinical practice are analyzed.

Meta-analysis of SGLT2 inhibitors and stroke risk in type 2 diabetic patients / 中华内分泌代谢杂志

Objective To evaluate the effects of sodium-glucose cotransporter 2 ( SGLT2) inhibitors on the stroke risk for patients with type 2 diabetes mellitus (T2DM). Methods A systemic meta-analysis including 30 random control trails ( RCTs) was performed to compare the risk of stroke between type 2 diabetic patients treated with SGLT2 inhibitors and control drugs. Then their bias risk and quality were assessed and meta-analysis was conducted using Stata12.0 software. Results Thirty RCTs enrolling 74456 participants were selected for meta-analysis. The stroke incidence in the group receiving SGLT2 inhibitor monotherapy or combination therapy did not significantly differ from that in control group, with relative risk (RR) 1.01 (95％CI 0.93-1.10, P=0.978) and 1.00 (95％CI 0.92-1.09, P=0. 874 ) , respectively. Three SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin did not increase the risk of stroke, with similar RR values ( RR=0.91, 0.99, 1.13, respectively) . Subgroup analyses showed that there was no correlation between SGLT2 inhibitors and stroke risk in different gender, age, diabetes duration, body mass index, or HbA1C levels. Conclusions Whether administered as monotherapy or add-on therapy, SGLT2 inhibitors did not increase stroke incidence, and there were no significant within-class differences.

New anti-diabetic agents

Diabetes mellitus is characterized by hyperglycemia due to insulin deficiency and/or insulin resistance. Cardiovascular disease (CVD) is a major comorbidity of type 2 diabetes mellitus, and is the most common cause of death in people with diabetes mellitus. Several clinical trials have addressed the long-term effects of near-normoglycemia on CVD, but did not find evidence of an effect. However, some recent clinical trials of sodium glucose cotransporter 2 inhibitors (EMPA-REG [Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes Trial], CANVAS [Canagliflozin Cardiovascular Assessment Study]) or glucagon-like peptide-1 agonists (LEADER [Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation], SUSTAIN-6 [Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes]) showed very promising results regarding the prevention of CVD. In this review, I discuss some of these new anti-diabetic agents and present clinical information regarding these drugs.

Uso de la dapagliflozina en el tratamiento de la diabetes mellitus tipo 2 / Use of dapagliflozin in the treatment of type 2 diabetes mellitus

Introducción: la dapagliflozina es un inhibidor del cotransportador sodio-glucosa tipo 2, un nuevo grupo de fármacos que disminuyen la glucemia, con bajo riesgo de hipoglucemia y con discreta pérdida de peso. Objetivo: describir algunos aspectos de interés sobre el uso de la dapagliflozina en el tratamiento de los pacientes con diabetes mellitus tipo 2, para lo cual, se realizó una revisión de varios artículos publicados sobre el tema, a través de algunas bases de datos y de los buscadores habituales (PubMed, Cochrane, Google, y otros), teniendo en cuenta su calidad y actualidad, según criterio de los autores. Desarrollo: la dapagliflozina es administrada por vía oral, e inhibe la reabsorción de glucosa en el túbulo proximal renal y aumenta la excreción urinaria de glucosa (efecto glucosúrico). Se utiliza a una dosis de 10 mg diarios, sola o asociada a otros medicamentos normo o hipoglucemiantes. En ambos casos es capaz de disminuir los niveles de la hemoglobina glucosilada. Su efectividad es similar a las sulfonilureas. Los efectos adversos más frecuentes se relacionan con un incremento de las infecciones genitourinarias, cetoacidosis con glucemias no tan elevadas, y cáncer. Conclusiones: la dapagliflozina es efectiva en reducir los niveles de la hemoglobina glucosilada, el peso corporal y de la presión arterial en pacientes con diabetes mellitus tipo 2, sobre todo, cuando se adiciona a otros medicamentos como la metformina. Su uso debe ser considerado como un tratamiento coadyuvante, aunque su indicación se debe individualizar, debido a su costo y sus posibles efectos adversos(AU)

Introduction: dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, a new group of pharmaceuticals that reduce glycemia, with low risk of hypoglycemia and modest loss of weight. Objective: to describe some aspects of interest on the use of dapagliflozin in the treatment of patients with type 2 diabetes mellitus for which several articles published on this topic were reviewed through some databases and the regular searchers (PubMed, Cochrane, Google and others), taking into account their quality and topicality, according to the authors' criteria. Development: dapagliflozin is orally administered and inhibits the re-absorption of glucose in the renal proximal tubule and increases the urinary glucose excretion (glycosuric effect). The dose is 10 mg daily, single or combined with other normoglycemic and hypoglycemic drugs. In both cases, it is able to diminish the levels of glycosylate hemoglobin. The effectiveness of this new drug is similar to that of the sulfonylureas. The most frequent effects are related to increase in genitourinary infections, ketoacidosis with not so high glycemia values and cancer. Conclusions: dapagliflozin is effective for the reduction of levels of glycosylate hemoglobin, body weight and blood pressure in patients with type 2 diabetes mellitus, mainly when added to other drugs like metformin. It should be considered as a coadjuvant treatment, although it should be prescribed on an individual footing due to its cost and possible adverse effects(AU)