Patients with diabetes who reported use of sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, or metformin prior to COVID-19 infection were associated with lower COVID-19–related adverse outcomes during hospitalization.
Use of glucose-lowering drugs was shown to reduce risk of COVID-19–related adverse outcomes among patients with diabetes who were diagnosed and hospitalized with COVID-19, according to study findings published today in JAMA Network Open.
Diabetes is a known risk factor for SARS-CoV-2 infection and related adverse outcomes. Researchers explained that, “Risk and severity of infection in patients with diabetes and COVID-19 are associated with increased angiotensin-converting enzyme 2 expression, increased furin levels, impaired T-cell function, and increased interleukin-6, which makes it possible for diabetes to promote COVID-19 infection because of increased viral entry into cells and impaired immune response.”
Standard of care glucose-lowering therapies for diabetes have been shown, albeit in conflicting findings, to have possible benefits regarding morbidity and mortality among patients with diabetes who become infected with COVID-19.
The study authors conducted a systematic review and meta-analysis to further assess the association between COVID-19–related adverse outcomes and antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19.
Randomized clinical trials and observational studies available on the PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov databases from inception to September 5, 2022, were included in the analysis.
Eligible studies were conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection. Studies had to include at least 2 of the following glucoselowering therapies as interventions: sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones, secretagogues, α-glucosidase inhibitors (AGIs), and insulin.
Pairwise comparisons were conducted between each therapy using relative effect tables with adverse outcomes expressed as log of odds ratio (logOR), in which negative values indicate superiority.
Of 1802 studies initially identified, 31 observational studies (3,689,010 patients with diabetes hospitalized for COVID-19) met the criteria for further analysis. Mean age was similar across the studies (range, 55-85 years), with the proportion of male participants indicated to be primarily between 32% and 72%.
Findings revealed significant differences between the glucose-lowering therapies. SGLT2 inhibitors were shown to be associated with relatively lower risks of adverse outcomes compared with insulin (logOR, 0.91; 95% credible interval [CrI], 0.57-1.26), DPP-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and AGIs (logOR, 0.50; 95% CrI, 0.00-1.01).
Additionally, GLP-1 RAs were superior to the DPP-4 inhibitors (logOR, 0.44; 95% CrI, 0.12-0.74) and insulin (logOR, 0.74; 95% CrI, 0.41-1.08), and insulin was inferior to metformin (logOR, 0.71; 95% CrI, 0.48-0.96), DPP-4 inhibitors (logOR, 0.31; 95% CrI, 0.05-0.58), secretagogues (logOR, 0.54; 95% CrI, 0.27-0.82), and thiazolidinediones (logOR, 0.61; 95% CrI, 0.17- 1.05).
Based on the surface under the cumulative ranking curves value, SGLT2 inhibitors were associated with the lowest probability for adverse outcomes (6%), followed by GLP-1 RAs (25%) and metformin (28%), whereas insulin was associated with a higher risk of adverse outcomes. A sensitivity analysis revealed that the study was reliable.
Researchers noted that due to the use of only observational studies, the results of this analysis should be interpreted as associations. Moreover, they said that the results of this study may be affected by diabetes comorbidities at baseline, baseline glycemic control, diabetes duration, and diabetes type, which were not assessed in this study.
Zhu Z, Zeng Q, Liu Q, Wen J, Chen G. Association of glucose-lowering drugs with outcomes in patients with diabetes before hospitalization for COVID-19: a systematic review and network meta-analysis. JAMA Netw Open. 2022;5(12):e2244652. doi:10.1001/jamanetworkopen.2022.44652