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GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes.
Marfella, R, Prattichizzo, F, Sardu, C, Rambaldi, PF, Fumagalli, C, Marfella, LV, La Grotta, R, Frigé, C, Pellegrini, V, D'Andrea, D, et al
Cardiovascular diabetology. 2024;(1):10
Abstract
BACKGROUND Few studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI). METHODS We recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c < 7% at admission were considered in good glycemic control and maintained the same glucose-lowering regimen, while those with poor glycemic control (HbA1c ≥ 7%), at admission or during follow-up, were prescribed either a SGLT-2i or a GLP-1RA to obtain a SGLT-2i/GLP-1RA combination therapy. The primary outcome was the incidence of major adverse cardiovascular events (MACE) defined as cardiovascular death, re-acute coronary syndrome, and heart failure related to AMI during a 2-year follow-up. After 3 months, the myocardial salvage index (MSI) was assessed by single-photon emission computed tomography. FINDINGS Of the 537 subjects screened, 443 completed the follow-up. Of these, 99 were treated with SGLT-2i, 130 with GLP-1RA, and 214 with their combination. The incidence of MACE was lower in the combination therapy group compared with both SGLT-2i and GLP-1RA treated patients, as assessed by multivariable Cox regression analysis adjusted for cardiovascular risk factors (HR = 0.154, 95% CI 0.038-0.622, P = 0.009 vs GLP-1RA and HR = 0.170, 95% CI 0.046-0.633, P = 0.008 vs SGLT-2i). The MSI and the proportion of patients with MSI > 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups. INTERPRETATION The combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.
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New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.
Pantea Stoian, A, Bica, IC, Salmen, T, Al Mahmeed, W, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, et al
Diabetes therapy : research, treatment and education of diabetes and related disorders. 2024;(1):33-60
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Abstract
INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.
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Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.
Ceriello, A, Rodbard, HW, Battelino, T, Brosius, F, Cosentino, F, Green, J, Ji, L, Kellerer, M, Koob, S, Kosiborod, M, et al
Cardiovascular diabetology. 2023;(1):277
Abstract
In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.
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The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.
Ceriello, A, Lucisano, G, Prattichizzo, F, La Grotta, R, Frigé, C, De Cosmo, S, Di Bartolo, P, Di Cianni, G, Fioretto, P, Giorda, CB, et al
The Lancet regional health. Europe. 2023;:100666
Abstract
BACKGROUND A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. METHODS Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0-1, 0-2, 0-3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. FINDINGS Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063-1.365). The introduction of SGLT-2i during the exposure periods of 0-1 and 0-2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). INTERPRETATION Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. FUNDING This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.
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SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes.
Marfella, R, Sardu, C, D'Onofrio, N, Fumagalli, C, Scisciola, L, Sasso, FC, Siniscalchi, M, Marfella, LV, D'Andrea, D, Minicucci, F, et al
BMC medicine. 2023;(1):71
Abstract
BACKGROUND No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). METHODS We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. RESULTS Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241-0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157-0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. CONCLUSIONS SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.
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Telemedicine for diabetes management during COVID-19: what we have learnt, what and how to implement.
Rosta, L, Menyhart, A, Mahmeed, WA, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, Cosentino, F, et al
Frontiers in endocrinology. 2023;:1129793
Abstract
The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine's advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient's glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.
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The Dual Pandemics of COVID-19 and Obesity: Bidirectional Impact.
Kapoor, N, Kalra, S, Al Mahmeed, W, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, Cosentino, F, et al
Diabetes therapy : research, treatment and education of diabetes and related disorders. 2022;(10):1723-1736
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Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been shown to disrupt many organ systems in the human body. Though several medical disorders have been affected by this infection, a few illnesses in addition may also play a role in determining the outcome of COVID-19. Obesity is one such disease which is not only affected by the occurrence of COVID-19 but can also result in a worse clinical outcome of COVID-19 infection. This manuscript summarizes the most recent evidence supporting the bidirectional impact of COVID-19 and obesity. It highlights how the presence of obesity can be detrimental to the outcome of COVID-19 in a given patient because of the mechanical limitations in lung compliance and also by the activation of several thrombo-inflammatory pathways. The sociodemographic changes brought about by the pandemic in turn have facilitated the already increasing prevalence of obesity. This manuscript highlights the importance of recognizing these pathways which may further help in policy changes that facilitate appropriate measures to prevent the further worsening of these two pandemics.
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Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health.
Lo Presti, E, Nuzzo, D, Al Mahmeed, W, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, Cosentino, F, et al
Biochimica et biophysica acta. Molecular basis of disease. 2022;(12):166559
Abstract
Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.
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Post-COVID syndrome, inflammation, and diabetes.
Rizvi, AA, Kathuria, A, Al Mahmeed, W, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, Cosentino, F, et al
Journal of diabetes and its complications. 2022;(11):108336
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Abstract
The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.
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Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence.
Mainas, G, Nibali, L, Ide, M, Mahmeed, WA, Al-Rasadi, K, Al-Alawi, K, Banach, M, Banerjee, Y, Ceriello, A, Cesur, M, et al
Metabolites. 2022;(1)
Abstract
Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.