Comment on “Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational data

2018 ◽  
Vol 21 (2) ◽  
pp. 444-445 ◽  
Author(s):  
Patrick B. Ryan ◽  
Norm Rosenthal
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Observational Data ◽  
Real World ◽  
Comparative Effectiveness ◽  
Meta Analysis ◽  
Sglt2 Inhibitors

Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis

2018 ◽  
Vol 25 (5) ◽  
pp. 495-502 ◽  
Author(s):  
Muhammad Shariq Usman ◽  
Tariq Jamal Siddiqi ◽  
Muhammad Mustafa Memon ◽  
Muhammad Shahzeb Khan ◽  
Wasiq Faraz Rawasia ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Cardiovascular Effects ◽  
Sglt2 Inhibitors ◽  
Cardiac Events ◽  
Adverse Cardiac Events

Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors. Only studies with a follow-up period of at least 24 weeks and reporting at least one cardiovascular outcome were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results Thirty-five eligible studies (canagliflozin, nine; empagliflozin, eight; dapagliflozin, 18), consisting of 34,987 patients with type 2 diabetes mellitus were included. Pooled results show that SGLT2 inhibitors, when compared to placebo, significantly reduce all-cause mortality (OR 0.79, 95% CI 0.70–0.89; P < 0.001), major adverse cardiac events (OR 0.8, 95% CI 0.76–0.92; P < 0.001), non-fatal myocardial infarction (OR 0.85, 95% CI 0.73–0.98; P = 0.03) and heart failure/hospitalisation for heart failure (OR 0.67, 95% CI 0.59–0.76; P < 0.001) in patients with type 2 diabetes mellitus. No significant difference was noted in the occurrence of stroke (OR 1.02, 95% CI 0.85–1.21; P = 0.87), atrial fibrillation (OR 0.61, 95% CI 0.31–1.19; P = 0.15) or unstable angina (OR 0.95, 95% CI 0.73–1.25; P = 0.73). In addition, there was no heterogeneity between different drugs in the SGLT2 inhibitor class for all of the clinical outcomes studied ( I2 = 0). Conclusions SGLT2 inhibitors significantly reduce the incidence of mortality, major adverse cardiac events, non-fatal myocardial infarction and heart failure in patients with type 2 diabetes mellitus. Subtypes of SGLT2 inhibitors appear to have similar cardiovascular effects.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals Heart failure among people with Type 2 diabetes mellitus: real‐world data of 289 954 people from a diabetes database

2019 ◽  
Vol 37 (8) ◽  
pp. 1291-1298
Author(s):  
D. Stoyanova ◽  
B. Stratmann ◽  
A. Schwandt ◽  
N. Heise ◽  
S. Mühldorfer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Real World ◽  
Real World Data ◽  
World Data

scholarly journals The effect of sodium-glucose link transporter 2 inhibitors on heart failure end points in people with type 2 diabetes mellitus: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Thomas Simon James Crabtree ◽  
Robert EJ Ryder
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Data Extraction ◽  
Meta Analysis ◽  
Incidence Rates ◽  
Cardiovascular Outcomes ◽  
Bias Assessment

Sodium-glucose linked transporter 2 inhibitors (SGLT2i) have been demonstrated to improve cardiovascular outcomes. In particular, SGLT2i appear to be beneficial in improving heart failure outcomes in people with and without diabetes. The aim of this review was to synthesis current evidence from randomised controlled trials (RCTs) comparing SGLT2i to placebo in adults with type 2 diabetes mellitus. The outcomes of interest were rate hospitalisation due to heart failure (primary), death due to heart failure (secondary) and incidence rates of heart failure (secondary).Methods: Searches were performed using recognised terms in MedLine, EMBASE, Pubmed and CINAHL. Studies were included if they compared an SGLT2i to inhibitor in an RCT and contained data for an outcome of interest. Studies were reviewed for inclusion by two people (TSJC and REJR) and data extraction and bias assessment were performed using a modified Cochrane’s data extraction tool and bias assessment tool. Meta-analysis of hazard ratios was performed in RevMan 5.4 using generic inverse variance and a fixed effects model where possible.Results: 2,850 records were identified of which 11 were eventually included, covering 9 clinical studies. Eight of these were suitable for meta-analysis for the outcome of hospitalisation due to heart failure – the pooled hazard ratio was found to be 0.69 (95% CI 0.63, 0.75). Interstudy heterogeneity was minimal (I2 0%) Only one study contained outcomes for death specifically due to heart failure, but its results were not significant. No current studies report incidence rates of new heart failure diagnosis.Conclusion: SGLT2is reduce the rates of hospitalisation due to heart failure in people with type 2 diabetes. This may help mediate the improvements seen in all cardiovascular outcomes, especially when assessed as a composite. More evidence is needed to support their use in reduce mortality due to heart failure and incidence rates of new heart failure in this high-risk cohort.

scholarly journals Targeting the DPP-4-GLP-1 pathway improves exercise tolerance in heart failure patients: a systematic review and meta-analysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chengcong Chen ◽  
Ying Huang ◽  
Yongmei Zeng ◽  
Xiyan Lu ◽  
Guoqing Dong
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Exercise Tolerance ◽  
Meta Analysis ◽  
Heart Failure Patients ◽  
Improve Exercise Tolerance

Abstract Background The most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus. Methods An electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O2 consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death. Result After the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality. Conclusion Our results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.

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