Dataset Information

The Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis.

ABSTRACT:

Background and aims

During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes.

Methods and results

Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients.

Conclusion

Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. Registration number: PROSPERO-CRD42020221951.

SUBMITTER: Han T

PROVIDER: S-EPMC8349690 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsThis study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis.ResultsThe pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%.ConclusionMetformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin.Systematic review registrationPROSPERO (CRD42021288200).

Project description:IntroductionPatients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications.MethodologyStudy is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed.ResultsOf 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies' outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257-0.719) and metformin use (OR 0.769; 95% CI 0.643-0.920), risk factors were insulin use (1.411; 95%CI 1.167-1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027-1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448-0.823), repaglinide use (OR 0.765; 95% CI 0.593-0.986) and metformin use (OR 0.857; 95% CI 0.770-0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568-1.019).ConclusionT2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed.