Semaglutide 1 mg once weekly may mitigate the risks of serious infection and COVID-19 events in individuals with T2D and CKD.In a prespecified secondary analysis of the phase III FLOW trial, semaglutide reduces the risk of serious infections and COVID-19 events in individuals with type 2 diabetes (T2D) and chronic kidney disease (CKD).
Compared with placebo, semaglutide significantly reduced the composite risk of first infection serious adverse event (SAE), first hospitalization due to infection, or all-cause death (24.3 percent vs 29.8 percent; hazard ratio [HR], 0.79; p=0.0002). [Nephrol Dial Transplant 2026;doi:10.1093/ndt/gfag036]
The semaglutide group also had lower risks of infection SAE (17.9 percent vs 21.3 percent; HR, 0.81; p=0.0070), COVID-19 AE (20.3 percent vs 22.9 percent; HR, 0.84; p=0.0190), COVID-19 SAE (6.7 percent vs 8.8 percent; HR, 0.74; p=0.0155), and hospitalization due to infection (17.5 percent vs 20.4 percent; HR, 0.83; p=0.0147) than the placebo group.
With semaglutide, the most common infection SAEs were COVID-19 pneumonia (3.9 percent), other pneumonia (3.7 percent), and COVID-19 infection (3.3 percent).
HbA1c, albuminuria
The reduction in the risk of the primary outcome was greater among participants with baseline HbA1c >8 percent vs ≤8 percent (HR, 0.63 vs 0.93; pinteraction=0.0027), as were the reductions in infection SAE (HR, 0.64 vs 1.00; pinteraction=0.0041) and COVID-19 AE risk (HR, 0.63 vs 1.02; pinteraction=0.0014).
Baseline urine albumin-to-creatinine ratio (≥2,000 mg/g vs <100 mg/g) also appeared to have an impact on the risk of the primary outcome (HR, 0.53 vs 0.90; pinteraction=0.0367), infection SAEs (HR, 0.58 vs 0.98; pinteraction=0.2634), and COVID-19 AEs (HR, 0.88 vs 1.33; pinteraction=0.0914).
These interactions suggest a greater potential benefit of semaglutide on infection risk among individuals with poorer glycaemic control and greater baseline albuminuria, the researchers said.
High-risk population
Respiratory infections are major complications in CKD patients. The co-occurrence of T2D and CKD further exacerbates the severity of infectious outcomes and increases mortality risk. [J Am Soc Nephrol 2013;24:302-308; Indian J Nephrol 2022;32:327-333]
“Individuals with T2D and CKD who develop infections represent an especially high-risk population who are more likely to progress to kidney failure, experience cardiovascular events, or die,” the researchers noted.
In FLOW, 3,533 participants (mean age 66.7 years) were randomized 1:1 to once-weekly SC semaglutide 1 mg or matching placebo. Approximately 70 percent of the participants were men, and about one-quarter were Asian.
Of note, the COVID-19 pandemic occurred while the trial was being conducted, with the most severe phase of the pandemic overlapping with the study period. After the pandemic began, the trial protocol was amended, and local guidance was adjusted to alleviate the risk of COVID-19 exposure to participants and staff, the researchers noted.
“The particular attention to infection management provided an opportunity to assess the impacts of the COVID-19 pandemic in a patient population at high risk of developing serious complications,” they said.
However, because different vaccine types were administered at various times, the investigators noted that this may have precluded assessment of how vaccines influenced infection-related or other outcomes. The findings may also not be applicable to a lower-risk CKD cohort, as approximately 95 percent of the participants had high- to very-high-risk CKD as per the KDIGO* criteria. [Kidney Int 2024;105:S117-S314]
Furthermore, most of the results captured infections—including COVID-19—with serious clinical manifestations, excluding virus-positive cases with mild (or no) symptoms, and FLOW was not powered for subgroup analyses, they added.
“[Despite these limitations, the results underscore the] potential role of SC semaglutide 1 mg once weekly in mitigating the risks of serious infection and COVID-19 events in individuals with T2D and CKD, highlighting important clinical benefits beyond kidney, cardiovascular, and metabolic outcomes,” the investigators concluded.