Dipeptidyl peptidase 4 (DPP4) inhibitor and outcome from coronavirus disease 2019 (COVID-19) in diabetic patients: a systematic review, meta-analysis, and meta-regression

Hariyanto, Timotius Ivan; Kurniawan, Andree

doi:10.1007/s40200-021-00777-4

Cited by 40 publications

(31 citation statements)

References 31 publications

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“…One meta-analysis of six studies (heterogeneity [ I 2 ]: 54%) and another of seven studies ( I 2 : 55%) published in December 2020 and January 2021, respectively, revealed no significant difference in the risk for the development of a fatal or severe course of illness with the use of DPP-4is in patients with COVID-19 [ 31 , 32 ]. Two subsequent meta-analyses with very low heterogeneity, published in February 2021 and March 2021 and included nine and ten studies, respectively, came to similar conclusions [ 33 , 34 ], with the exception of some benefits of in-hospital use of DPP-4is. More recently, Rakhmat et al published a meta-analysis of nine studies and reported that taking DPP-4is was associated with lower mortality in COVID-19 patients with diabetes mellitus [ 35 ].…”

Section: Discussionmentioning

confidence: 75%

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

et al. 2021

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Introduction 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). Methods 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. Results 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). Conclusions 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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Section: Discussionmentioning

confidence: 75%

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

et al. 2021

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“…[2][3][4][5][6][7] Several therapies had been proposed to control and manage these conditions. [8][9][10][11][12][13][14] Recently the use of GLP1-RA, as one alternative to treat DM patients, had shown promising effect to reduce excessive inflammation-induced acute lung injury and improving Covid-19 outcome. [15] In addition to stimulating postprandial insulin secretion, GLP1-RA also seems to have beneficial properties such antiinflammatory, anti-obesogenic, pulmonary protective effects and gut microbiome modulating effects.…”

Section: Introductionmentioning

confidence: 99%

Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression

Hariyanto

Intan

Hananto

et al. 2021

Diabetes Research and Clinical Practice

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Aims GLP-1RA has many beneficial properties, including anti-inflammatory, anti-obesogenic, pulmonary protective effects as well as beneficial impact on gut microbiome. However, the evidence regarding the benefit of GLP-1RA in Covid-19 patients with diabetes is still unclear. This study sought to analyze the benefit of pre-admission use of GLP-1RA in altering the mortality outcomes of coronavirus disease 2019 (Covid-19) patients with diabetes mellitus. Methods Using specific keywords, we comprehensively searched the potential articles on PubMed, Europe PMC, and medRxiv database until June 12 th , 2021. All published studies on Covid-19 and GLP-1RA were retrieved. Statistical analysis was conducted using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. Results A total of 9 studies with 19,660 diabetes mellitus patients who were infected by SARS-CoV-2 were included in the meta-analysis. Our data suggested that pre-admission use of GLP-1RA was associated with reduction in mortality rate from Covid-19 in patients with diabetes mellitus (OR 0.53; 95%CI: 0.43 – 0.66, p <0.00001, I 2 = 0%, random-effect modelling). Further analysis showed that the associations were not influenced by age ( p =0.213), gender (p=0.421), hypertension (p=0.131), cardiovascular disease (p=0.293), nor the use of metformin (p=0.189) and insulin (p=0.117). Conclusions Our study suggests that pre-admission use of GLP-1RA may offer beneficial effects on Covid-19 mortality in patients with diabetes mellitus. However, more randomized clinical trials are required to confirm this conclusion.

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“…Good glucose control has been demonstrated to exert a protective effect in the context of the development and outcomes of COVID-19 (3)(4)(5), and strict glucose management on admission for COVID-19 cases has been suggested regardless of diabetes status (6). The role of glycemic control strategies, such as several antidiabetic drugs including metformin and DPP-4 inhibitors in the efficacy and safety of COVID-19 and diabetes has been established (7,8). However, whether insulin injection has some effect on the development of COVID-19 remains inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis

2021

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Background and ObjectiveRecently, insulin treatment has been found to be associated with increased mortality and other adverse outcomes in patients with coronavirus disease 2019 (COVID-19) and diabetes, but the results remain unclear and controversial, therefore, we conducted this meta-analysis.MethodsFour databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify all studies concerning insulin treatment and the adverse effects of COVID-19, including mortality, incidence of severe/critical complications, in-hospital admission and hospitalization time. To assess publication bias, funnel plots, Begg’s tests and Egger’s tests were used. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the effect of insulin therapy on mortality, severe/critical complications and in-hospital admission. The association between insulin treatment and hospitalization time was calculated by the standardized mean difference (SMD) with 95% CIs.ResultsEighteen articles, involving a total of 12277 patients with COVID-19 and diabetes were included. Insulin treatment was significantly associated with an increased risk of mortality (OR=2.10; 95% CI, 1.51-2.93) and incidence of severe/critical COVID-19 complications (OR=2.56; 95% CI, 1.18-5.55). Moreover, insulin therapy may increase in-hospital admission in patients with COVID-19 and diabetes (OR=1.31; 95% CI, 1.06-1.61). However, there was no significant difference in the hospitalization time according to insulin treatment (SMD=0.21 95% CI, -0.02-0.45).ConclusionsInsulin treatment may increase mortality and severe/critical complications in patients with COVID-19 and diabetes, but more large-scale studies are needed to confirm and explore the exact mechanism.

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Dipeptidyl peptidase 4 (DPP4) inhibitor and outcome from coronavirus disease 2019 (COVID-19) in diabetic patients: a systematic review, meta-analysis, and meta-regression

Cited by 40 publications

References 31 publications

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

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

Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression

Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis

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