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 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 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 Effects of SGLT2 Inhibitors on Renal Outcomes in Patients With Chronic Kidney Disease: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Ning Li ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
Ping Wei ◽  
Yuan Gui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Renal Outcomes ◽  
Underlying Diseases

Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear.Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function.Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) &gt;300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR&lt;60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR &gt; 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR&lt;60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR &gt; 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR&lt;60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR &gt; 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48).Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals Potential Impact on Lipoprotein Subfractions in Type 2 Diabetes

2019 ◽  
Vol 12 ◽  
pp. 117955141986681 ◽  
Author(s):  
Yuka Kamijo ◽  
Hideto Ishii ◽  
Tomohiko Yamamoto ◽  
Kunihisa Kobayashi ◽  
Hiroyuki Asano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Sglt2 Inhibitor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Lipoprotein Subfractions ◽  
Cholesterol Levels

Introduction: Recently, the sodium-glucose cotransporter2 (SGLT2) inhibitor empagliflozin has been shown to lower cardiovascular risk among diabetic patients. It is intriguing that some SGLT2 inhibitors have been found to increase low-density lipoprotein (LDL) cholesterol levels, while the relevance to high-density lipoprotein (HDL) cholesterol is unknown. Although the inhibitory effect of SGLT2 inhibitors on glucose reabsorption may accelerate compensatory lipid metabolism and subsequently reduce body weight and affect the lipid profile, much remains unclear about this mechanism. Therefore, we conducted this study to investigate in detail how canagliflozin affects lipoprotein fractions including LDL and HDL subclasses. Materials and Methods: This study is a multicenter prospective study. The participants were patients with 22 type 2 diabetes (60.7 ± 11.6 years, 59.1% of men) who had HbA1c ⩾ 7.0% and consented to participate in the study. They were administered 100 mg canagliflozin orally once per day. Biochemistry test and cholesterol levels of 20 lipoprotein fractions (G1-G20) using high performance liquid chromatography methods were examined before and after 12 weeks of treatment period. Results: Significant decreases were observed in the participants’ body weight (69.7 to 67.9 kg, P < .001), systolic blood pressure (129.3 to 119.5 mm Hg, P < .01), and HbA1c (8.5% to 7.4%, P < .001). Cholesterol levels in the 20 lipoprotein fractions increased for very large HDL (G14, G15) and large HDL (G16) ( P < .05). Conclusions: Reduction in body weight, improvement of blood glucose levels, and increases in very large HDL and large HDL subclasses were observed after canagliflozin treatment. These beneficial changes might contribute to subsequent suppression of cardiovascular outcomes.

scholarly journals Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
David S. H. Bell
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Case Reports ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Endogenous Insulin ◽  
Large Randomized Clinical Trial ◽  
Endogenous Insulin Production

SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in better glycemic control in most patients but also in some patients’ less hypoglycemia, weight loss, and decreased doses of insulin. In type 1 diabetesCandida albicansvaginitis and balanitis may occur more frequently than in type 2 diabetes. These cases show that a large randomized clinical trial of SGLT2 inhibitors in type 1 diabetes needs to be performed.

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