scholarly journals Are SGLT2 polymorphisms linked to diabetes mellitus and cardiovascular disease? Prospective study and meta-analysis

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Heinz Drexel ◽  
Andreas Leiherer ◽  
Christoph H. Saely ◽  
Eva Maria Brandtner ◽  
Kathrin Geiger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Nucleotide Polymorphisms ◽  
Cardiovascular Morbidity And Mortality ◽  
Slc5a2 Gene

Abstract Inhibition of the sodium glucose co-transporter 2 (SGLT2) reduces cardiovascular morbidity, and mortality in patients with type 2 diabetes mellitus (T2DM) with atherosclerotic, cardiovascular disease. So far, a link between common genetic variations of the SGLT2 encoding gene SLC5A2 and glucose homeostasis as well as cardiovascular disease has not been established. The present study, therefore, aimed to investigate SLC5A2 single nucleotide polymorphisms (SNPs) in relation to type 2 diabetes and coronary artery disease (CAD) and prospectively the incidence of cardiovascular events. We genotyped the SLC5A2 tagging SNPs rs9934336, rs3813008, and rs3116150 in a total of 1684 high risk cardiovascular patients undergoing coronary angiography, including 400 patients with T2DM. Additionally, we performed a meta-analysis combining results from the present study and the literature. Variant rs9934336 was significantly associated with decreased HbA1c (P = 0.023). Further, rs9934336 was significantly inversely associated with the presence of T2DM in univariate (OR = 0.82 [0.68–0.99]; P = 0.037) as well as in multivariate analysis (OR = 0.79 [0.65–0.97]; P = 0.023). The association between rs9934336 and T2DM was confirmed in a meta-analysis including results from two previous observations which by themselves had failed to show a significant association of the polymorphism with T2DM (OR = 0.86 [0.78–0.95]; P = 0.004). Polymorphisms rs3813008 and rs3116150 were associated neither with glycemic parameters nor with T2DM. None of the SNPs tested was significantly associated with the baseline presence of CAD or the incidence of cardiovascular events. We conclude that genetic variation within the SLC5A2 gene locus is significantly related to the manifestation of T2DM.

scholarly journals 459 Evaluation of LDL-C reductions by siRNA treatment with inclisiran in patients with diabetes mellitus, metabolic syndrome or neither

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
R. Scott Wright ◽  
David Kallend ◽  
Kausik K Ray ◽  
Lawrence Leiter ◽  
Wolfgang Koenig ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Controlled Trial ◽  
Atherosclerotic Cardiovascular Disease ◽  
Double Blind ◽  
Sirna Treatment ◽  
Patients With Diabetes

Abstract Aims Patients with diabetes (DM) and metabolic syndrome (MS) have elevated risks for atherosclerotic cardiovascular disease (ASCVD). Aggressive LDL-C lowering reduces risks. Inclisiran, a new siRNA, lowers LDL-C and was evaluated in patients with Type 2 diabetes (DM), metabolic syndrome (MS) without DM or neither (N) in the ORION-10 trial. Methods ORION-10 was a double-blind, randomized, placebo controlled trial evaluating inclisiran in 1561 patients with ASCVD on maximally tolerated therapy for lowering LDL-C. 781 inclisiran (INC) participants and 780 placebo (P) patients received 1.5 mL SQ tx at Days 1, 90, then every 6 months until Day 540. We evaluated the time adjusted change in LDL-C from baseline after Days 90–540 in DM (n = 702), MS (n = 455) and N participants (n = 404). Results There were no differences in baseline demographics and background therapies between INC and P. Statins were utilized in 89.8% INC and 88.7% of P. High intensity statins were utilized in 67.2% of INC and 68.8% of P; ezetimibe in 10.2% of NC and 9.5% of P participants. INC reduced LDL-C by − 54.4% (−58.3, −50.6 95% CI) in DM, (P < 0.001), −58.6% (−62.3, −54.8), P < 0.001 in-MS and −56.0% (−60.2, −51.7), in N subjects P < 0.001 (see Figure). Conclusions Inclisiran potently and durably reduces LDL-C across patients with DM, MS and those with neither, demonstrating potent efficacy and durability across glycaemic categories. Inclisiran may also represent a potent LDL-C lowering treatment for those with DM and MS.

scholarly journals Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (35) ◽  
pp. 3346-3358 ◽  
Author(s):  
Fabio Marsico ◽  
Stefania Paolillo ◽  
Paola Gargiulo ◽  
Dario Bruzzese ◽  
Simona Dell’Aversana ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Receptor Agonists ◽  
Type 2 Dm ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Aims  Glucose-lowering, glucagon-like peptide-1 (GLP-1) receptor agonists reduce incidence of major cardiovascular (CV) events in patients with Type 2 diabetes mellitus (DM). However, randomized clinical trials reported inconsistent effects on myocardial infarction (MI) and stroke, and limited data in DM patients without established CV disease (CVD). Very recently, new relevant evidence was available from additional CV outcome trials (CVOTs) that also included large subgroups of patients with DM without established CVD. Thus, the aim of this meta-analysis was to investigate the effects of GLP-1 receptor agonists on major CV events and safety in DM patients with and without established CVD. Methods and results  In this trial-level meta-analysis, we analysed data from randomized placebo-controlled CVOTs assessing efficacy and safety of GLP-1 receptor agonists in adult patients with Type 2 DM. We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases for eligible trials. Of 360 articles identified and screened for eligibility, seven CVOTs were included, with an overall of 56 004 patients included. The difference in efficacy with respect to the major adverse cardiovascular events (MACE) primary endpoint (including CV mortality, non-fatal MI, and non-fatal stroke) between patients with established CVD and patients with CV risk factors only was not significant [pooled interaction effect, expressed as ratio of hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.85–1.34]. In the analysis of the whole population of DM patients, GLP-1 receptor agonists showed a significant 12% reduction in the hazard of the three-point MACE composite endpoint (HR 0.88, 95% CI 0.80–0.96) and a significant reduction in the risk of CV mortality (HR 0.88, 95% CI 0.79–0.98), all-cause mortality (HR 0.89, 95% CI 0.81–0.97), fatal and non-fatal stroke (HR 0.84, 95% CI 0.76–0.94), and heart failure (HF) hospitalization (HR 0.92, 95% CI 0.86–0.97). No significant effect was observed for fatal and non-fatal MI (HR 0.91, 95% CI 0.82–1.02), although in a sensitivity analysis, based on a less conservative statistical approach, the pooled HR become statistically significant (HR 0.91, 95% CI 0.83–1.00; P = 0.039). No excess of hypoglycaemia, pancreatitis, and pancreatic cancer was observed between GLP-1 receptor agonists and placebo. Conclusion  Glucagon-like peptide-1 receptor agonists significantly reduce MACE, CV and total mortality stroke, and hospitalization for HF, with a trend for reduction of MI, in patients with Type 2 DM with and without established CVD.

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