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Journal ArticleDOI

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study.

TL;DR: In this paper, the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM) was investigated.
Abstract: To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM). A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population. A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35–0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39–1.08; p = 0.099). The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.

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Citations
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Journal ArticleDOI
TL;DR: In this paper , the effects of pre-admission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes were compared.
Abstract: Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes.A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses.We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), I2 86%], glucagon-like peptide-1 receptor agonist (GLP-1RA) [0.51 (0.37-0.69), I2 85%], and sodium-glucose transporter-2 inhibitor (SGLT-2i) [0.60 (0.40-0.88), I2 91%]. Dipeptidyl peptidase-4 inhibitor (DPP-4i) [1.23 (1.07-1.42), I2 82%] and insulin [1.70 (1.33-2.19), I2 97%] users were more likely to die during hospitalization. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor were mortality neutral [0.92 (95% CI 0.83-1.01, I2 44%), 0.90 (95% CI 0.71-1.14, I2 46%), and 0.61 (95% CI 0.26-1.45, I2 77%), respectively]. The sensitivity analysis indicated that our findings were robust.Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.

24 citations

Journal ArticleDOI
TL;DR: Investigation of serum circulating DPP4 activity in patients with COVID-19 disease found a significant decrease was found in study groups of higher disease severity and is a strong prognostic biomarker of mortality.
Abstract: Aim: To investigate the serum circulating DPP4 activity in patients with COVID-19 disease. Materials & methods: Serum samples from 102 hospitalized COVID-19 patients and 43 post-COVID-19 plasma donors and 39 SARS-CoV-2 naive controls and their medical data were used. Circulating DPP4 activities according to different COVID-19 disease peak severity (WHO) groups at sampling and at peak were assessed. Results: A significant decrease (p < 0.0001) in serum DPP4 activity was found in study groups of higher disease severity. When the circulating DPP4 activity was assessed as a prognostic marker, the logistic regression (p = 0.0023) indicated that the enzyme activity is a predictor of mortality (median 9.5 days before death) with receiver operating characteristic area under the curves of 73.33% (p[area = 0.5] < 0.0001) as single predictor and 83.45% (p[area = 0.5] < 0.0001) in combination with age among hospitalized patients with COVID-19. Conclusion: Decreased circulating DPP4 activity is associated with severe COVID-19 disease and is a strong prognostic biomarker of mortality.

11 citations

Journal ArticleDOI
TL;DR: It is demonstrated that the use of DPP-4i by patients with T2DM in catching COVID-19 does not affect the mortality due to CO VID-19, the severity of COVID -19 disease, and 3-month post-discharge mortality.
Abstract: OBJECTIVE We aim to investigate whether the use of dipeptidyl peptidase inhibitors (DPP-4i) affects the severity of disease, hospital mortality, and 3-month post-discharge mortality in type 2 diabetes mellitus (T2DM) individuals with coronavirus disease 2019 (COVID-19) infection. METHODS The study included 217 patients with type 2 diabetes hospitalized due to COVID-19 between March and October 2020. The patients included in the study were divided into two groups those using DPP-4i and those not using DPP-4i. Demographic characteristics, laboratory parameters, accompanying risk factors, concomitant comorbidities, hospital mortality, clinical course, and 3-month post-discharge mortality were compared between the patients who used DPP-4i and those who did not use. RESULTS The duration of hospitalization was 10.96±9.16 days in the group using DPP-4i, 12.22±9.1 days in the group not using DPP-4i, and when both groups were evaluated together, it was determined as 11.91±9.11 days. The hospitalization periods were similar between DPP-4i users and non-DPP-4i users (p=0.384). The need for mechanical ventilation (p=0.478 OR 0.710 95% confidence interval [CI], 0.274–1.836) and high-flow nasal cannula (p=0.457, OR: 0.331, 95% CI: 0.41–2.67) were similar between DPP-4i users and non-users. It was determined that the mortality (p=0.208, OR: 0.409, 95% CI: 0.117–1.429) and 3-month post-discharge mortality (p=0.383) were similar in the group using DPP-4i and those not using DPP-4i. CONCLUSION This study demonstrated that the use of DPP-4i by patients with T2DM in catching COVID-19 does not affect the mortality due to COVID-19, the severity of COVID-19 disease, and 3-month post-discharge mortality.

3 citations

Journal ArticleDOI
TL;DR: In this paper , the authors evaluated different noninsulin AGMs in patients with COVID-19 infection and found that patients with diabetes are more likely to suffer COVID•19 complications.
Abstract: Patients with diabetes are more likely to suffer COVID‐19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID‐19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID‐19.

3 citations

Journal ArticleDOI
10 Mar 2022
TL;DR: In this article , the authors present a narrative review of the literature in order to set light into the relationship between COVID-19 infection and DM/hyperglycemia, and the risk may be higher for those without pre-existing DM.
Abstract: It was previously reported that subjects with diabetes mellitus (DM) are more vulnerable to several bacterial or viral infections. In the era of coronavirus disease 2019 (COVID-19) pandemic, it is reasonable to wonder whether DM is a risk factor for COVID-19 infection, too. It is not yet clear whether DM increases the risk for contracting COVID-19 infection or not. However, patients with DM when infected are more likely to develop severe or even fatal COVID-19 disease course than patients without DM. Certain characteristics of DM patients may also deteriorate prognosis. On the other hand, hyperglycemia per se is related to unfavorable outcomes, and the risk may be higher for COVID-19 subjects without pre-existing DM. In addition, individuals with DM may experience prolonged symptoms, need readmission, or develop complications such as mucormycosis long after recovery from COVID-19; close follow-up is hence necessary in some selected cases. We here present a narrative review of the literature in order to set light into the relationship between COVID-19 infection and DM/hyperglycemia.

2 citations

References
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Journal ArticleDOI
TL;DR: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.
Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...

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Journal ArticleDOI
TL;DR: The findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality, and clinicians should increase their awareness of kidney patients with severe CO VID-19.

1,994 citations

Journal ArticleDOI
14 Mar 2013-Nature
TL;DR: Dipeptidyl peptidase 4 (DPP4; also known as CD26) is identified as a functional receptor for hCoV-EMC and will contribute critically to the understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
Abstract: Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.

1,743 citations

Journal ArticleDOI
TL;DR: Previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19 were confirmed, and the results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs in this clinical context.
Abstract: Background Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensi...

1,050 citations

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