No abstract available.
Glucosides ; Glycated Hemoglobin A ; Sodium-Glucose Transporter 2 Inhibitors ; Diabetes Mellitus, Type 2 ; Glomerular Filtration Rate

No abstract available.
Glucosides ; Glycated Hemoglobin A ; Sodium-Glucose Transporter 2 Inhibitors ; Diabetes Mellitus, Type 2 ; Glomerular Filtration Rate

Introduction: Sodium glucose transporter 2 (SGLT2) inhibitors are a new class of anti-diabetic agents that not only lower down blood sugar but can potentially cause weight loss and decrease in blood pressure. The aim of this meta-analysis is to evaluate the magnitude of changes in blood pressure and safety parameters with the use of SGLT2 inhibitors among adult patients with type 2 diabetes mellitus (DM). Methods: Randomized controlled trials (RCTs) were retrieved from electronic databases. We used the method recommend by the Cochrane Collaboration to perform a meta-analysis of RCTs of SGLT2 inhibitor for type 2 DM. Results: Of 137 studies retrieved in the literature search, 28 were eligible for inclusion. A total of 23,728 patients with average age of 50-63 years old, when SGLT2 inhibitor were compared with placebo or active comparators there were statistically significant reduction in systolic (MD: -4.01, 95% CI -4.03 to -3.99) and diastolic blood pressure (MD: -1.48, 95% CI -1.49 to -1.46). There were no significant differences in the incidence of hypoglycemia (RR: 0.94, 95% CI 0.90 to 0.99, P<0.00001) between SGLT2 inhibitors and control groups. The incidence of urinary tract infections was similar between the SGLT2 inhibitors and the control groups (RR: 1.12, 95% CI 1.01 to 1.25, P=1.00). There was statistically greater incidence of orthostatic hypotension among patients given SGLT2 inhibitors than the control group (RR: 1.41, 95% CI 1.14 to 1.75, P=0.99). Conclusion Treatment with SGLT2 inhibitor provided statistically significant reductions in systolic and diastolic blood pressure in patients with type 2 DM compared with placebo or other anti-diabetic agents.
Blood Pressure ; Sodium-Glucose Transporter 2 Inhibitors ; Diabetes Mellitus, Type 2

Diabetes Mellitus, Type 2 ; Humans ; Myocardial Infarction/drug therapy* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*

Cardiovascular Diseases ; Diabetes Mellitus, Type 2 ; Humans ; Sodium-Glucose Transporter 2 Inhibitors

Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Arrhythmias, Cardiac/etiology* ; Glucose ; Sodium

Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Arrhythmias, Cardiac/etiology* ; Glucose ; Sodium

The employment of sodium-glucose cotransporter 2 (SGLT-2) inhibitors in the treatment of diabetes mellitus and diabetic kidney disease (DKD) becomes a hot topic in recent years. Compared with traditional glucose-lowering drugs, SGLT-2 inhibitors present distinctive advantages in renal and cardiovascular protection. The mechanisms for renal protection include attenuating glomerular hyperfiltration, lowering serum uric acid, alleviating tubular lesions and regulating intrarenal renin-angiotensin-aldosterone system (RAAS) dysfunction. In addition, the lowering blood pressure, blunting blood glucose fluctuation, increasing insulin sensitivity, optimizing energy metabolism and body fat distribution account for the cardiovascular protective effects of SGLT-2 inhibitors. However, their potential adverse reactions and safety concerns should be carefully addressed in clinical usage.
Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; drug therapy ; Humans ; Hypoglycemic Agents ; pharmacology ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; pharmacology ; Uric Acid

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na⁺/H⁺ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Animals ; Diabetes Mellitus ; Diabetes Mellitus, Type 2/drug therapy* ; Glucose ; Humans ; Mice ; Myocardial Infarction/metabolism* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Ventricular Remodeling

BACKGROUND: Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials. METHODS: This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation. RESULTS: We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population. CONCLUSIONS The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.
Benzhydryl Compounds ; Canagliflozin ; Cardiovascular Diseases ; China ; Diabetes Mellitus, Type 2/drug therapy* ; Glucosides ; Humans ; Male ; Sodium-Glucose Transporter 2 Inhibitors ; Tertiary Care Centers