scholarly journals Effects of SGLT2 Inhibitors on Atherosclerosis: Lessons from Cardiovascular Clinical Outcomes in Type 2 Diabetic Patients and Basic Researches

2021 ◽  
Vol 11 (1) ◽  
pp. 137
Author(s):  
Jing Xu ◽  
Taro Hirai ◽  
Daisuke Koya ◽  
Munehiro Kitada
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter ◽  
Reduce Blood Glucose

Atherosclerosis-caused cardiovascular diseases (CVD) are the leading cause of mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective oral drugs for the treatment of T2DM patients. Multiple pre-clinical and clinical studies have indicated that SGLT2 inhibitors not only reduce blood glucose but also confer benefits with regard to body weight, insulin resistance, lipid profiles and blood pressure. Recently, some cardiovascular outcome trials have demonstrated the safety and cardiovascular benefits of SGLT2 inhibitors beyond glycemic control. The SGLT2 inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin reduce the rates of major adverse cardiovascular events and of hospitalization for heart failure in T2DM patients regardless of CVD. The potential mechanisms of SGLT2 inhibitors on cardioprotection may be involved in improving the function of vascular endothelial cells, suppressing oxidative stress, inhibiting inflammation and regulating autophagy, which further protect from the progression of atherosclerosis. Here, we summarized the pre-clinical and clinical evidence of SGLT2 inhibitors on cardioprotection and discussed the potential molecular mechanisms of SGLT2 inhibitors in preventing the pathogenesis of atherosclerosis and CVD.

scholarly journals Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus

2015 ◽  
Vol 309 (11) ◽  
pp. F889-F900 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Luke Norton ◽  
Ralph A. DeFronzo
Keyword(s):  
Type 2 Diabetes ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Renal Tubules ◽  
Type 2 Diabetic Patients ◽  
Antidiabetic Agents ◽  
Sodium Glucose Cotransporter ◽  
The Us ◽  
Established Relationship

Hyperglycemia is the primary factor responsible for the microvascular, and to a lesser extent macrovascular, complications of diabetes. Despite this well-established relationship, approximately half of all type 2 diabetic patients in the US have a hemoglobin A1c (HbA1c) ≥7.0%. This is associated in part with the side effects, i.e., weight gain and hypoglycemia, of currently available antidiabetic agents and in part with the failure to utilize medications that reverse the basic pathophysiological defects present in patients with type 2 diabetes. The kidney has been shown to play a central role in the development of hyperglycemia by excessive production of glucose throughout the sleeping hours and enhanced reabsorption of filtered glucose by the renal tubules secondary to an increase in the threshold at which glucose spills into the urine. Recently, a new class of antidiabetic agents, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, has been developed and approved for the treatment of patients with type 2 diabetes. In this review, we examine their mechanism of action, efficacy, safety, and place in the therapeutic armamentarium. Since the SGLT2 inhibitors have a unique mode of action that differs from all other oral and injectable antidiabetic agents, they can be used at all stages of the disease and in combination with all other antidiabetic medications.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

2021 ◽  
Vol 8 ◽  
Author(s):  
Dan Xu ◽  
Owain Chandler ◽  
Cleo Wee ◽  
Chau Ho ◽  
Jacquita S. Affandi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Diabetic Patients ◽  
Atherosclerotic Cardiovascular Disease ◽  
Healthy Individuals ◽  
Type 2 Diabetic Patients ◽  
Sodium Glucose Cotransporter ◽  
Type 2 Diabetic

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

scholarly journals Cardiovascular outcomes of type 2 diabetic patients treated with DPP‑4 inhibitors versus sulphonylureas as add-on to metformin in clinical practice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Carlos Bazo-Alvarez ◽  
Kingshuk Pal ◽  
Tra My Pham ◽  
Irwin Nazareth ◽  
Irene Petersen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Social Deprivation ◽  
Smoking Status ◽  
Cardiovascular Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Prior History ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
History Of

AbstractDPP-4 inhibitors (DPP-4i) and sulphonylureas remain the most widely prescribed add-on treatments after metformin. However, there is limited evidence from clinical practice comparing major adverse cardiovascular events (MACE) in patients prescribed these treatments, particularly among those without prior history of MACE and from vulnerable population groups. Using electronic health records from UK primary care, we undertook a retrospective cohort study with people diagnosed type-2 diabetes mellitus, comparing incidence of MACE (myocardial infarction, stroke, major cardiovascular surgery, unstable angina) and all-cause mortality among those prescribed DPP-4i versus sulphonylureas as add-on to metformin. We stratified analysis by history of MACE, age, social deprivation and comorbidities and adjusted for HbA1c, weight, smoking-status, comorbidities and medications. We identified 17,570 patients prescribed sulphonylureas and 6,267 prescribed DPP-4i between 2008–2017. Of these, 16.3% had pre-existing MACE. Primary incidence of MACE was similar in patients prescribed DPP-4i and sulphonylureas (10.3 vs 8.5 events per 1000 person-years; adjusted Hazard Ratio (adjHR): 0.94; 95%CI 0.80–1.14). For those with pre-existing MACE, rates for recurrence were higher overall, but similar between the two groups (21.8 vs 17.2 events per 1000 person-years; adjHR: 0.93; 95%CI 0.69–1.24). For those aged over 75 and with BMI less than 25 kg/m2 there was a protective effect for DPP-I, warranting further investigation. Patients initiating a DPP-4i had similar risk of cardiovascular outcomes to those initiating a sulphonylurea. This indicates the choice should be based on safety and cost, not cardiovascular prognosis, when deciding between a DPP-4i or sulphonylurea as add-on to metformin.

scholarly journals Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
In-Chang Hwang ◽  
Goo-Yeong Cho ◽  
Yeonyee E. Yoon ◽  
Jin Joo Park ◽  
Jun-Bean Park ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic
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