The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
Yidan Chen, Xingfei Lv, Sang Lin, Mohammad Arshad, Mengjun Dai
Frontiers in Endocrinology, doi:10.3389/fendo.2022.895458
Aims: This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. Methods: We 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. Results: The 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), sodiumglucose 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 nonusers. 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%.
Conclusion: Metformin, 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
AUTHOR CONTRIBUTIONS YC, XL, and SL: Conceptualization, methodology, data curation, investigation, and writing -original draft preparation. MA and MD: Supervision, writing -reviewing and editing, and funding acquisition. All authors contributed to the article and approved the submitted version.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2022.895458/ full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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'abstract': '<jats:sec><jats:title>Aims</jats:title><jats:p>This study aimed to assess the impact of '
'different antidiabetic agents on individuals with diabetes and '
'COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We 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 '
'<jats:italic>via</jats:italic> traditional pairwise meta-analysis and Bayesian network '
'meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The '
'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&gt;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%.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Metformin, '
'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.</jats:p></jats:sec><jats:sec><jats:title>Systematic Review '
'Registration</jats:title><jats:p>PROSPERO (CRD42021288200)</jats:p></jats:sec>',
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'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fendo.2022.895458/full',
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'date-time': '2022-05-27T12:17:46Z',
'timestamp': 1653653866000},
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'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fendo.2022.895458/full'}},
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'relation': {},
'ISSN': ['1664-2392'],
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'container-title-short': 'Front. Endocrinol.',
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