Semaglutide vermindert infectierisico bij diabetes en chronische nierziekte

BACKGROUND: In the FLOW trial (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 (AEs), 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 (CI)] 0.79 [0.69-0.89]; P = 0.0002). This risk reduction was greater in subgroups with baseline HbA1c > 8% (HR 0.63 [0.52-0.76]) versus ≤ 8% (HR 0.93 [0.79-1.11]; Pinteraction = 0.0027), and UACR ≥2000 mg/g (HR [95% CI] 0.53 [0.39-0.72]) versus UACR <100 mg/g (HR 0.90 [0.58-1.39]; Pinteraction = 0.0367). The semaglutide group had a lower rate of infection SAEs (17.9% versus 21.3%; P = 0.0070), COVID-19 SAEs (6.7% versus 8.8%; P = 0.0155), COVID-19 AEs (20.3% versus 22.9%; P = 0.0190), and hospitalization due to infection (17.5% versus 20.4%; P = 0.015). 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.