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

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.