The Association between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis (preprint)

ABSTRACT

Background: During the current Coronavirus Disease 2019 (COVID-19) pandemic, diabetic patients face disproportionately more. Anti-inflammatory effects of hypoglycemic agents have been reported, and their effects in patients with diabetes and COVID-19 remain controversial. This study was performed to clarify this association.Methods: Relevant literature was searched on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese periodical service platform VIP Database, Sinomed (China Biology Medicine, CBM), MedRxiv, PubMed, ScienceDirect, Web of Science, Ovid Databases (LWW), Springer Link, Wiley Online Library, Oxford Academic, Nature Press Group, Cochrane Library, and BMJ Evidence-Based Medicine up to November 14, 2020. Only observational studies of hypoglycemic agents vs. other drugs or therapy in adult diabetic patients with COVID-19 were included. Data of death and poor composite outcomes were extracted. The pooled effects of hypoglycemic agents on mortality and poor composite outcomes of COVID-19 in diabetic patients, pooled ORs along with 95% CIs, were calculated using the fixed-effects or random-effects models based on heterogeneity assessment. Registration number of PROSPERO is CRD42020221951.Findings: 16 studies were included in the qualitative analysis and 14 studies with 13,371 patients were included in quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality in diabetic patients with COVID-19 (pooled OR=0·56, 95% CI, 0·39-0·81, p=0·002), especially home use of metformin (pooled OR=0·60, 95%CI, 0·40-0·88, p=0·01). but in-hospital use of metformin was associated with statistically non-significant lower mortality (pooled OR=0·44, 95%CI, 0·15-1·33, p=0·14) or poor composite outcomes (pooled OR=0·93, 95% CI, 0·79-1·11, p=0·44). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR=0·63, 95% CI, 0·26-1·56, p=0·32) or poor composite outcomes of COVID-19 in diabetic patients (pooled OR=0·96, 95% CI, 0·74-1·26, p=0·78).Interpretation: Home use of metformin might be beneficial in decreasing mortality in diabetic patients infected with SARS-CoV-2. There is insufficient evidence to conclude that metformin and other hypoglycemic agents are associated with poor composite outcomes. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed.Funding Statement This study is financially supported by Hunan Provincial Key Laboratory of Clinical Epidemiology (grant number 2020ZNDXLCL002).Declaration of Interests We declare no competing interests.