Adverse Outcomes After COVID-19 Onset Less Likely With Certain Antihyperglycemics

The lowest risk for adverse outcomes after COVID-19 onset in patients with diabetes was observed among those receiving sodium-glucose cotransporter-2 inhibitors.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2) inhibitor use before the onset of COVID-19 infection is associated with a lower risk for COVID-19-related adverse outcomes in patients with diabetes. These study results were published in JAMA Network Open.

In this systematic review and network meta-analysis, researchers evaluated 31 randomized-controlled trials and observational studies in which patients with diabetes received antihyperglycemic medications for at least 14 days before the onset of COVID-19 infection. Two independent reviewers performed a blinded review of the data.  Studies included in the meta-analysis were those that assessed a composite adverse outcome of the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, and in-hospital mortality. Pooled outcomes were assessed using metaregression, with adjustments for mean age and sex.

There were 3,689,010 patients included in the analysis, representing 148 treatment groups. Across all studies analyzed, the mean age range was 55 to 85 years, 32% to 72% of patients were men, and most patients had diabetes for 10 or more years. At baseline, HbA1c levels ranged between 7.1% to greater than 8.7%. Prior to COVID-19 onset, 37.09% of patients reported metformin use, 19.53% reported insulin use, and 3.33% reported SGLT-2 inhibitor use.

The findings of this meta-analysis provide information regarding routine antihyperglycemic medications and COVID-19-related adverse outcomes.

A total of 22,006 adverse outcomes were reported. The researchers found that insulin use was associated with the greatest risk for adverse outcomes after COVID-19 onset. The lowest risk for adverse outcomes was observed among patients who used SGLT-2 inhibitors, followed by those who used glucagon-like peptide-1 receptor agonists and those who used metformin.

These results were confirmed in a sensitivity analysis. In addition, the metaregression analysis showed that the risk for adverse outcomes associated with antihyperglycemic treatment type did not differ by mean age and sex.

This review was limited by the inclusion of only observational studies and differences among the patients in regard to COVID-19 vaccination status, variants, and inpatient protocols. The researchers also did not assess diabetes-related comorbidities at baseline, baseline glycemic control, diabetes duration, or diabetes type.

According to the researchers “The findings of this meta-analysis provide information regarding routine antihyperglycemic medications and COVID-19-related adverse outcomes.

References:

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 systemic review and network meta-analysis. JAMA Netw Open. 2022;5(12):e2244652. doi:10.1001/jamanetworkopen.2022.44652