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0 0.5 1 1.5 2+ Hospitalization, DPP-4is 22% Improvement Relative Risk Hospitalization, insulin o.. 26% Hospitalization, GLP-1 RAs 17% Metformin for COVID-19  Greco et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 44,977 patients in Italy (January 2020 - December 2021) Study compares with DPP-4is, results vs. placebo may differ Lower hospitalization with metformin (not stat. sig., p=0.11) Greco et al., Biomedicines, August 2023 Favors metformin Favors DPP-4is

The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study

Greco et al., Biomedicines, doi:10.3390/biomedicines11082292
Aug 2023  
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Retrospective 76,764 diabetes patients in Italy, showing that patients on metformin had lower rates of COVID-19 hospitalization compared to those on insulin/insulin secretagogues, GLP-1 receptor agonists, and DPP-4 inhibitors. Metformin vs. no metformin results are not provided. The most relevant result for COVID-19 and metformin may be the DPP-4i comparison, based on the DPP-4i group being the most similar to the metformin group in terms of baseline COVID-19 risk and confounders. Patients on insulin/secretagogues may have more severe or advanced diabetes.
risk of hospitalization, 22.0% lower, OR 0.78, p = 0.11, treatment 30,238, control 2,264, DPP-4is, RR approximated with OR.
risk of hospitalization, 26.0% lower, OR 0.74, p = 0.006, treatment 30,238, control 14,739, insulin or insulin secretagogues, RR approximated with OR.
risk of hospitalization, 17.0% lower, OR 0.83, p = 0.54, treatment 30,238, control 317, GLP-1 RAs, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Greco et al., 18 Aug 2023, retrospective, Italy, peer-reviewed, 8 authors, study period January 2020 - December 2021, this trial compares with another treatment - results may be better when compared to placebo.
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The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study
Salvatore Greco, Vincenzo M Monda, Giorgia Valpiani, Nicola Napoli, Carlo Crespini, Fabio Pieraccini, Anna Marra, Angelina Passaro
Biomedicines, doi:10.3390/biomedicines11082292
Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19-and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period.
Supplementary Materials: The following supporting information can be downloaded at: https://, Figure S1 : Prevalence of diabetes in the overall adult subjects in the districts of Ferrara and Romagna (A), percentage of diabetic subjects in the districts of Ferrara and Romagna and overall average of diabetic subjects (B); Figure S2 : Evaluation of the length of stay in terms of days in the subgroup of patients treated with the four main antidiabetic treatments (A); length of stay among the same four subgroups of inpatients and comparison between COVID-19 and non-COVID-19 subjects (B); Table S1 : The institutions serving the districts of Ferrara and Romagna participating in the study; Table S2 : MACEs and antidiabetic drugs. Author Contributions: S.G.: acquisition, analysis and interpretation of data, drafting the article; V.M.M.: the conception and design of the study, drafting the article and revising it critically for important intellectual content; G.V. and N.N.: collection and processing of data; C.C., F.P. and A.M.: acquisition of information concerning drug prescriptions and dispensation, processing data relating to local pharmacies; A.P.: conception and design of the study; revising the article critically for important intellectual content; and final approval of the version to be submitted. All authors have read and agreed to the published version of the manuscript. Informed Consent Statement: Not applicable. ..
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