ABSTRACT
The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.
ABSTRACT
The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption-resulting in glycosuria-and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The latter is a pandemic that has the potential of developing into a severe illness manifesting as systemic inflammatory response syndrome, acute respiratory distress syndrome, multi-organ involvement and shock. In addition, advanced age and male sex and certain underlying health conditions, like type 2 diabetes mellitus (T2DM), predispose to a higher risk of greater COVID-19 severity and mortality. This calls for an urgent identification of antidiabetic agents associated with more favourable COVID-19 outcomes among patients with T2DM, as well as recognition of their potential underlying mechanisms. It is crucial that individuals with T2DM be kept under very stringent glycaemic control in order to avoid developing various cardiovascular, renal and metabolic complications associated with more severe forms of COVID-19 that lead to increased mortality. The use of novel antidiabetic agents dipeptidyl peptidase 4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in subjects with T2DM may have beneficial effects on COVID-19 outcomes. However, relevant studies either show inconsistent results (DPP4i) or are still too few (SGLT2i and GLP-1RAs). Further research is therefore needed to assess the impact of these agents on COVID-19 outcomes.
ABSTRACT
Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.