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

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

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

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

Objective: To analyze the effects of different types of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on 24-hour ambulatory blood pressure in patients with type 2 diabetes mellitus and hypertension. Method: In this meta-analysis, we searched for randomized controlled trials on the effect of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension. Three databases, namely PubMed, Web of Science and Cochrane Library, were searched. The search was organized on the concept of 3 conceptual groups: the first group contained terms used to describe SGLT2i, the second group contained terms related to blood pressure, and the third group contained terms used to describe randomized controlled trials. The search time was from the establishment of the database to December 2020. The inclusion and exclusion criteria were formulated in accordance with the requirements of the Cochrane systematic review. According to whether the heterogeneity of the study was significant or not, a random effect model or a fixed effect model were used to conduct the analysis on the impact of different types of SGLT2i on 24-hour ambulatory blood pressure and day and night blood pressure in patients with type 2 diabetes and hypertension. Further subgroup analysis was performed to define potential factors, which might lead to clinical heterogeneity. Results: Seven clinical trials were finally included. The result of the meta-analysis showed that compared with placebo group, SGLT2i could reduce the 24-hour dynamic systolic blood pressure of patients with type 2 diabetes and hypertension by 4.36 mmHg (1 mmHg=0.133 kPa). Reduction was 4.59, 3.74, 5.06, and 3.64 mmHg by canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin respectively; SGLT2i could reduce the 24-hour dynamic diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.20 mmHg, and the reduction was 2.30, 1.22, 2.00, and 2.69 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin respectively. SGLT2i could reduce the daytime systolic blood pressure of patients with type 2 diabetes and hypertension by 5.25 mmHg, and reduction was 5.38, 4.87, 6.00, and 4.37 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. Simultaneously, SGLT2i could reduce the diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.62 mmHg, and the reduction was 2.56, 2.47, and 2.80 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. SGLT2i could reduce the nighttime systolic blood pressure of patients with type 2 diabetes and hypertension by 3.62 mmHg, and the reduction was 2.09, 2.06, 3.92, and 2.45 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. At the same time, SGLT2i could reduce the nighttime diastolic blood pressure of patients with type 2 diabetes and hypertension by 1.60 and 1.51 mmHg, the reduction was 1.53 and 2.58 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. Conclusion: SGLT2i can reduce 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Hypertension/drug therapy* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*