Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial.

BACKGROUND

In the FLOW trial (Evaluate Renal Function with Semaglutide Once-Weekly; ClinicalTrials.gov, NCT03819153), once-weekly subcutaneous semaglutide 1.0 mg versus placebo reduced the risk of major kidney, cardiovascular (CV) and mortality outcomes in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD). This pre-specified analysis assesses the impact of semaglutide on risks of serious infections and coronavirus disease 2019 (COVID-19) in the FLOW trial.

METHODS

The main outcome was a three-component composite [time from randomization to first infection serious adverse event (SAE), first hospitalization due to infection, or all-cause death]. Other outcomes included all infection SAEs, COVID-19 adverse events, COVID-19 SAEs, death due to infection and death concurrent with a COVID-19 SAE.

RESULTS

Semaglutide reduced the risk of the main outcome versus placebo [hazard ratio (HR) (95% confidence interval) 0.79 (0.69-0.89); P = .0002]. This risk reduction was greater in subgroups with baseline hemoglobin A1c >8% [HR 0.63 (0.52-0.76)] versus ≤8% [HR 0.93 (0.79-1.11); Pinteraction = .0027], and urine albumin-to-creatinine ratio (UACR) ≥2000 mg/g [HR 0.53 (0.39-0.72)] versus UACR <100 mg/g [HR 0.90 (0.58-1.39); Pinteraction = .0367]. The semaglutide group had a lower rate of infection SAEs (17.9% versus 21.3%; P = .0070), COVID-19 SAEs (6.7% versus 8.8%; P = .0155), COVID-19 adverse events (20.3% versus 22.9%; P = .0190) and hospitalization due to infection (17.5% versus 20.4%; P = .015).

CONCLUSIONS

Semaglutide reduced risks of infection SAEs, hospitalization due to infection, and all-cause death with greater benefit among those with poorer glycemic control and greater baseline albuminuria. These findings support potential clinical benefits of semaglutide beyond kidney, CV and metabolic outcomes in high-risk patients with T2D and CKD.