scholarly journals Relationship Between HbA1c Level and Effectiveness of SGLT2 Inhibitors in Decompensated Heart Failure Patients with Type 2 Diabetes Mellitus

Author(s):  
Masaki Nakagaito ◽  
Teruhiko Imamura ◽  
Shuji Joho ◽  
Ryuichi Ushijima ◽  
Makiko Nakamura ◽  
...  
2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan

: 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.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chengcong Chen ◽  
Ying Huang ◽  
Yongmei Zeng ◽  
Xiyan Lu ◽  
Guoqing Dong

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.


2018 ◽  
Vol 36 (Supplement 1) ◽  
pp. e208-e209
Author(s):  
A.M. Gonzalez Gonzalez ◽  
P. Guardia Martinez ◽  
A.M. Garcia Bellon ◽  
D. Gaitan Roman ◽  
M. de Mora Martin

Kardiologiia ◽  
2019 ◽  
Vol 59 (4) ◽  
pp. 76-87 ◽  
Author(s):  
Zh. D. Kobalava ◽  
N. V. Yeshniyazov ◽  
V. V. Medovchshikov ◽  
E. R. Khasanova

Type 2 diabetes mellitus (T2DM) has gone beyond the professional interests of one specialty. T2DM, cardiovascular (CV) diseases and chronic kidney disease, considered from the standpoint of a single cardio-reno-metabolic continuum, place a heavy economic burden on society. At the same time, the improvement of diagnostic methods and medical technologies led to distinct decrease in the frequency and mortality from a number of complications of T2DM, including myocardial infarction and stroke, but other states took their place. Thus, heart failure (HF) has taken the position of one of the most frequent complications with average prevalence of 24–40 % and significant predominance of HF with preserved ejection fraction (HFpEF). According to this paradigm, HFpEF is not a disease of diastolic dysfunction, but a systemic disease, the central element of which is impaired renal function. All this together has a potential value for choosing the optimal therapy. In recent years the results of specially designed studies assessing the CV-safety of antidiabetic drugs from the groups of dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like preptide-1 (GLP-1) receptor agonists and sodium – glucose co-transporter-2 (SGLT2) inhibitors have become known. These drugs, except for SGLT2 inhibitors, by their mechanism of action affecting insulin resistance and hyperglycemia, demonstrated neutral or negative result on the frequency of hospitalizations due to HF. The EMPA-REG OUTCOME study with SGLT2, which has a special insulin-independent mechanism of action, demonstrated not only the efficacy and CV-safety of the drug in the form of a decrease in CV mortality by 38 %, but also a decrease in hospitalizations for HF by 35 %. Further studies with SGLT2 inhibitors confirmed positive effect on HF, indicating a class effect of the drugs. The recently completed study DECLARE-TIMI 58 proved the advantages of using dapagliflozin for the primary and secondary prevention of HF. This review highlights the prevalence of HF in diabetes mellitus, a new concept of the pathophysiology of HF, the main groups of sugar-lowering drugs and their effect on CV outcomes, in particular on HF. 


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