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

Metformin has robust glucose-lowering effects and multiple benefits beyond hypoglycemic effects. It can also be used in combination with various hypoglycemic drugs and is cost effective. In the absence of the strong indications of glucagon like peptide-1 receptor agonist (GLP-1RA) or sodium glucose cotransporter 2 inhibitor (SGLT2i) for cardiorenal protection, metformin should be used as the first-line pharmacological treatment for newly diagnosed type 2 diabetes and the basic drug for the combined treatment of hypoglycemic drugs. Metformin does not increase the risk of liver and kidney function damage, but patients with renal dysfunction should adjust the dosage of metformin based on estimated glomerular filtration rate (eGFR) levels. Moreover, the correct use of metformin does not increase the risk of lactic acidosis. Because long-term use of metformin is associated with a decrease in vitamin B₁₂ levels, patients with insufficient intake or absorption of vitamin B₁₂ should be regularly monitored and appropriately supplemented with vitamin B₁₂. In view of the new progress made in the basic and clinical research related to metformin, the consensus updating expert group updated the consensus on the basis of the Expert Consensus on the Clinical Application of Metformin (2018 Edition).
Humans ; Consensus ; Diabetes Mellitus, Type 2/complications* ; Hypoglycemic Agents ; Metformin/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Vitamins/therapeutic use* ; China

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

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

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

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

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*

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

We aimed to identify the clinical variables associated with a better glucose-lowering response to the sodium glucose cotransporter 2 inhibitor ipragliflozin in people with type 2 diabetes mellitus (T2DM). We especially focused on urinary glucose excretion (UGE). This was a single-arm multicenter prospective study. A total of 92 people with T2DM aged 20 to 70 years with glycosylated hemoglobin (HbA1c) levels ≥7.0% and ≤9.5% were enrolled. Ipragliflozin (50 mg) was added to the background therapy for these people for 12 weeks. After 3 months treatment with ipragliflozin, the mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of the people reached the HbA1c target of less than 7.0% (P<0.001). In addition, body weight, blood pressure, and lipid parameters were improved after ipragliflozin treatment (all P<0.001). The baseline HbA1c (r=0.66, P<0.001) and morning spot urine glucose to creatinine ratio (r=−0.30, P=0.001) were independently associated with the HbA1c reduction. Ipragliflozin treatment for 12 weeks improves glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicts a better glucose-lowering efficacy of ipragliflozin.
Blood Pressure ; Body Weight ; Creatinine ; Diabetes Mellitus, Type 2 ; Glucose ; Glycosuria ; Hemoglobin A, Glycosylated ; Prospective Studies ; Sodium ; Sodium-Glucose Transporter 2

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