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The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies

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Abstract

Background

Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19.

Methods

We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications.

Results

56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58–0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59–0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69–0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26–1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50–0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76–0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What’s more, metformin (OR 0.77; 95% CI 0.62–0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81–0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79–0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12–1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography.

Conclusion

Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.

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Data Availability

The datasets generated or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

Funding/Support: This work is supported by the National Natural Science Foundation of China (grant number 82070851). No financial disclosures.

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  1. Zhi-Hui Song and Qiao-Ming Huang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China

    Zhi-Hui Song, Qiao-Ming Huang, Shan-Shan Xu & Chao Zhang

  2. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

    Jian-Bo Zhou

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  1. Zhi-Hui Song
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Song, ZH., Huang, QM., Xu, SS. et al. The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies. Ther Innov Regul Sci (2024). https://doi.org/10.1007/s43441-024-00633-6

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