scholarly journals SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes?

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 14
Author(s):  
Yoshifumi Saisho
Keyword(s):  
Type 2 Diabetes ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Real World Data ◽  
Renal Outcomes ◽  
Urinary Glucose ◽  
Induce Weight Loss

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral hypoglycemic agents which increase urinary glucose excretion by suppressing glucose reabsorption at the proximal tubule in the kidney. SGLT2 inhibitors lower glycated hemoglobin (HbA1c) by 0.6–0.8% (6–8 mmol/mol) without increasing the risk of hypoglycemia and induce weight loss and improve various metabolic parameters including blood pressure, lipid profile and hyperuricemia. Recent cardiovascular (CV) outcome trials have shown the improvement of CV and renal outcomes by treatment with the SGLT2 inhibitors, empagliflozin, canagliflozin, and dapagliflozin. The mechanisms by which SGLT2 inhibitors improve CV outcome appear not to be glucose-lowering or anti-atherosclerotic effects, but rather hemodynamic effects through osmotic diuresis and natriuresis. Generally, SGLT2 inhibitors are well-tolerated, but their adverse effects include genitourinary tract infection and dehydration. Euglycemic diabetic ketoacidosis is a rare but severe adverse event for which patients under SGLT2 inhibitor treatment should be carefully monitored. The possibility of an increase in risk of lower-extremity amputation and bone fracture has also been reported with canagliflozin. Clinical trials and real-world data have suggested that SGLT2 inhibitors improve CV and renal outcomes and mortality in patients with type 2 diabetes (T2DM), especially in those with prior CV events, heart failure, or chronic kidney disease. Results of recent trials including individuals without diabetes may change the positioning of this drug as ″a drug for cardiorenal protection″. This review summarizes the potential of SGLT2 inhibitors and discusses their role in the treatment of T2DM.

scholarly journals Renal outcomes in Asian patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Shi-di Zhao ◽  
Ling Zhou ◽  
Yi-ying Tao ◽  
Yue Yue ◽  
Jia-xin Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Control Groups ◽  
Renal Outcomes ◽  
Randomized Controlled ◽  
Asian Patients

Abstract Aim This study investigated the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal outcomes in Asian patients with type 2 diabetes mellitus (T2DM). Materials and methods We searched Medline, EMBASE, and the Cochrane Library to identify randomized controlled trials published up to April 2020 that compared SGLT2 inhibitors with placebo or active comparator and reported any renal outcomes in Asian patients with T2DM. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals (CIs). Results We included 14 studies, totaling 3792 patients, in the analysis. In the short term, SGLT2 inhibitors significantly slowed estimated glomerular filtration rate (eGFR) decline (MD: 0.80; 95% CI: 0.66 to 0.94; p < 0.00001) and reduced Scr levels (SMD: − 0.17; 95% CI: − 0.23 to − 0.10; p < 0.00001) as compared with the control groups. The SGLT2 inhibitor group also had an advantage over the control group in lowering uric acid (UA) (SMD: − 1.2; 95% CI: − 1.30 to − 1.11; p < 0.00001). There was no significant difference in urinary albumin creatinine ratio (UACR) reduction between the SGLT2 inhibitor and control groups (MD: − 8.87; 95% CI: − 19.80 to 2.06; p = 0.11). However, dapagliflozin does appear to reduce albuminuria (p = 0.005). Lastly, SGLT2 inhibitors increased the incidence of adverse events (AEs) related to renal function (OR: 1.90; 95% CI: 1.24 to 2.91; p = 0.003), but did not increase the incidence of renal impairment (OR: 0.85; 95% CI: 0.40 to 1.81; p = 0.68). Conclusion The use of SGLT2 inhibitors in Asian patients with T2DM can help delay the decline of eGFR and reduce Scr and UA. Although SGLT2 inhibitors have no overall advantage in reducing albuminuria, dapagliflozin does appear to reduce albuminuria, and while they may increase the occurrence of AEs related to renal function, they do not increase the incidence of renal impairment.

scholarly journals The Effect of Long-term Sodium-glucose Cotransporter 2 Inhibitor Treatment on Renal Function in the Patients with Type 2 Diabetes

2020 ◽  
Vol 95 (4) ◽  
pp. 236-243
Author(s):  
Jong Ha Baek ◽  
Tae Jung Oh ◽  
Ju-Young Moon ◽  
Taehee Kim ◽  
Seung Hyu Ko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Renal Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Inhibitor Treatment

Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)

scholarly journals Empagliflozin and Cardio-renal Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease – Implications for Clinical Practice

2018 ◽  
Vol 14 (2) ◽  
pp. 40 ◽  
Author(s):  
David H Fitchett
Keyword(s):  
Type 2 Diabetes ◽  
Primary Outcome ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Outcome Study ◽  
Rapid Reduction ◽  
Renal Outcomes ◽  
Risk Of Progression ◽  
Cv Disease

In patients with type 2 diabetes (T2D), the excretion of glucose by the kidney with sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers glycosylated haemoglobin (HbA1c) levels, decreases body weight and visceral adiposity, as well as improving cardio-renal haemodynamics. Currently, four SGLT2 inhibitors are approved in the US and Europe to improve glycaemic control – empagliflozin, dapagliflozin, canagliflozin, and ertuglifozin. Recently, the SGLT2 inhibitor empagliflozin was approved by the FDA for the reduction of cardiovascular (CV) death in adults with T2D and CV disease (CVD). This approval was based on the findings of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study, which was the first study to show a significant reduction of a primary CV endpoint with a glucose-lowering agent. In this study, the primary outcome (CV mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was reduced by empagliflozin (10.5%; 490/4,687) compared with placebo (12.1%; 282/2,333); hazard ratio (HR), 0.86 (95% confidence interval [CI]: 0.74, 0.99). The primary outcome was driven by a large reduction of CV mortality (relative risk reduction [RRR], 38%). Empagliflozin also reduced all-cause mortality (RRR, 32%). Furthermore, empagliflozin reduced the adjudicated outcome of heart failure (HF) hospitalisation by 35% (HR, 0.65; 95% CI: 0.50, 0.85). Other non-adjudicated measures of HF outcomes were similarly reduced including investigator reported HF, the introduction of loop diuretics and death from HF. In the analysis of renal outcomes, incident or worsening nephropathy was reduced for empagliflozin (12.7%) compared with placebo (18.8%); HR, 0.61 (95% CI: 0.53, 0.70). Empagliflozin significantly reduced the risk of progression to macroalbuminuria (38%) and doubling of creatinine (44%), as well as the need of starting renal-replacement therapy (55%). The benefits of empagliflozin for the reduction of CV death, all-cause death and hospitalisation for HF were observed across a range of baseline subgroups such as HbA1c level and renal function (down to estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m2). The rapid reduction of HF outcomes with empagliflozin is observed across the spectrum of CVD and HF risk and represents a therapeutic advance in the prevention and perhaps also in the treatment of HF, an often poorly recognised complication of T2D. This review discusses the EMPA-REG OUTCOME study and the implications for treating patients with T2D and CVD.

scholarly journals Potential mechanisms underlying cardiovascular protection by sodium glucose cotransporter 2 inhibitors (empagliflozin)

2021 ◽  
Vol 10 (3) ◽  
pp. 79-89
Author(s):  
I. S. Sabirov ◽  
I. T. Murkamilov ◽  
V. V. Fomin
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Clinical Trial ◽  
Sodium Glucose Cotransporter ◽  
Pubmed Database ◽  
Urinary Glucose

The presented literature review is devoted to the cardioprotective capabilities of a new class of antihyperglycemic drugs - sodium-glucose cotransporter 2 inhibitors (SGLT2), which improve glycemic control through an insulin-independent mechanism of action associated with an increase in urinary glucose excretion. The article presents the results of large-scale clinical trials on the use of SGLT2 inhibitors in patients with and without diabetes, and with cardiovascular diseases or multiple cardiovascular risk factors. A number of the most frequently discussed cardiac specific mechanisms mediated by the SGLT2 inhibitor affecting the Abstract           state of the cardiovascular system are presented. Moreover, the article presents the results of a placebo-controlled clinical trial entitled “Empagliflozin reduces mortality in patients with type 2 diabetes at high cardiovascular risk” (EMPA-REG oUtcOmE) to analyze the cardioprotective capabilities of SGLT2 inhibitor empagliflozin in patients with type 2 diabetes and concomitant cardiovascular diseases. The article emphasizes the importance of further research to determine the degree of contribution of the above-mentioned mechanisms to the cardioprotective potential of SGLT2 inhibitors. PubMed database was used to identify relevant studies and systematic reviews.

Abstract P162: Comparison Of The Clinical Effect Of Empagliflozin On Glycemic And Non-glycemic Parameters In Japanese Patients With Type 2 Diabetes And Cardiovascular Disease Treated With Or Without Baseline Metformin

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Troponin I ◽  
Treatment Guidelines ◽  
Geometric Mean ◽  
Sglt2 Inhibitors ◽  
Hypoglycemic Agents ◽  
Clinical Parameters ◽  
Diabetes Status

Introduction: Recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors to be considered preferentially in patients with T2D at high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of metformin. Hypothesis: We assessed the hypothesis that the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin. Methods: This was a post hoc analysis of the Effect of Empagliflozin on Endothelial Function in Cardiovascular High Risk Diabetes Mellitus: Multi-Center Placebo-Controlled Double-Blind Randomized (EMBLEM) trial. All participants (n=105; women 31.4%; mean age 64.8 years) had both T2D and DVD and were randomized to either 24 weeks of empagliflozin 10mg daily or placebo. We assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. Results: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the change from baseline systolic blood pressure was greater in patients receiving metformin, compared to metformin-naïve patients (group difference -8.5 [95%CI -17.7 to 0.6 mmHg], p=0.066). Reduction in body mass index was significantly greater in patients receiving baseline metformin, relative to nonusers (-0.54 [95%CI -1.07 to -0.01] kg/m 2 , p=0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I was 0.74 (95%CI 0.59 to 0.92, p=0.009). No obvious difference was observed in glycemic parameters, such as fasting plasma glucose and HbA1c, between the baseline metformin users and nonusers. Conclusions: Our findings suggest empagliflozin has a partially different impact on clinical parameters according to whether or not metformin has been used at baseline. As clinical opportunities for prescribing SGLT2 inhibitors are likely to increase, further research is needed to investigate the effect of SGLT2 inhibitors on clinical parameters taking into account the background situation of hypoglycemic agents, such as metformin.

scholarly journals A Randomized Trial of Insulin Glargine plus Oral Hypoglycemic Agents versus Continuous Subcutaneous Insulin Infusion to Treat Newly Diagnosed Type 2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Shuo Lin ◽  
Mu Chen ◽  
Wanling Chen ◽  
Keyi Lin ◽  
Panwei Mu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Insulin Glargine ◽  
Basal Insulin ◽  
Insulin Infusion ◽  
Cell Function ◽  
Hypoglycemic Agents ◽  
Newly Diagnosed ◽  
Oral Hypoglycemic Agents

Aims. Basal insulin plus oral hypoglycemic agents (OHAs) has not been investigated for early intensive antihyperglycemic treatment in people with newly diagnosed type 2 diabetes. This study is aimed at comparing the short-term (over a period of 12 days) effects of basal insulin glargine plus OHAs and continuous subcutaneous insulin infusion (CSII) on glycemic control and beta-cell function in this setting. Methods. An open-label parallel-group study. Newly diagnosed hospitalized patients with type 2 diabetes and fasting plasma glucose (FPG) ≥11.1 mmol/L or glycated hemoglobin (HbA1c) ≥9% (75 mmol/mol) were randomized to CSII or insulin glargine in combination with metformin and gliclazide. The primary outcome measure was the mean amplitude of glycemic excursions (MAGE), and secondary endpoints included time to reach glycemic control target (FPG < 7 mmol/L and 2-hour postprandial plasma glucose < 10 mmol/L), markers of β-cell function, and hypoglycemia. Results. Subjects in the CSII (n=35) and basal insulin plus OHA (n=33) groups had a similar significant reduction from baseline to end of treatment in glycated albumin (−6.44 ± 3.23% and− 6.42 ± 3.56%, P=0.970). Groups A and B have comparable time to glycemic control (3.6 ± 1.2 days and 4.0 ± 1.4 days), MAGE (3.40 ± 1.40 mmol/L vs. 3.16 ± 1.38 mmol/L; p=0.484), and 24-hour mean blood glucose (7.49 ± 0.96 mmol/L vs. 7.02 ± 1.03 mmol/L). Changes in the C-peptide reactivity index, the secretory unit of islet in transplantation index, and insulin secretion-sensitivity index-2 indicated a greater β-cell function improvement with basal insulin plus OHAs versus CSII. Conclusions. Short-term insulin glargine plus OHAs may be an alternative to CSII for initial intensive therapy in people with newly diagnosed type 2 diabetes.

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