Insulin Therapy and Outcome of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression

Background: Currently, the relationship between insulin therapy and COVID-19 outcome is not yet established. Our study aims to evaluate the possible association between insulin and the composite poor outcome of COVID-19. Methods: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 12th, 2020. All articles published on COVID-19 and insulin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. Results: Our pooled analysis showed that insulin use was associated with composite poor outcomes of COVID-19 [OR 2.06 (95% CI 1.70 - 2.48), p < 0.00001, I2 = 83%, random- effect modelling], and its subgroup which comprised of risk of COVID-19 [OR 1.70 (95% CI 1.40 - 2.08), p < 0.00001, I2 = 34%, random-effect modelling], severe COVID-19 [OR 2.30 (95% CI 1.60 - 3.30), p < 0.00001, I2 = 88%, random-effect modelling], and mortality [OR 2.14 (95% CI 1.47 - 3.10), p < 0.0001, I2 = 85%, random-effect modelling]. Meta-regression showed that the association was influenced by age (p = 0.008), but not by diabetes p = 0.423) and cardiovascular disease (p = 0.086). Conclusion: Physicians should be more aware and take extra precautions with diabetes patients who use insulin therapy.