This prespecified analysis of the FLOW randomized clinical trial examined whether once-weekly subcutaneous semaglutide 1.0 mg affected risk of serious infections and COVID-19 outcomes among participants with type 2 diabetes (T2D) and chronic kidney disease (CKD). The parent FLOW trial previously demonstrated benefits of semaglutide for major kidney, cardiovascular, and mortality outcomes in this high-risk population. This analysis focused specifically on infection-related endpoints captured during the randomized trial.
The analysis was prespecified within the FLOW trial (ClinicalTrials.gov NCT03819153). The main outcome for this infection-focused analysis was a three-component composite: time from randomization to first infection serious adverse event (SAE), first hospitalization due to infection, or all-cause death. Secondary and 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. The abstract reports event rates, hazard ratios (HRs) with 95% confidence intervals (CIs), and P values for the main and several secondary outcomes.
Treatment with semaglutide was associated with a statistically significant reduction in the risk of the prespecified composite outcome compared with placebo. The reported hazard ratio was 0.79 (95% CI 0.69–0.89), with P = .0002, indicating a 21% relative risk reduction for the composite of infection SAE, hospitalization for infection, or all-cause death in the semaglutide group versus placebo.
The authors report lower event rates in the semaglutide arm for several infection-related endpoints. Specifically:
These figures indicate consistent reductions in both COVID-19–related events and broader infection-related hospitalizations and SAEs in participants randomized to semaglutide.
The magnitude of benefit for the composite infection outcome varied across prespecified subgroups:
Baseline glycemic control: Participants with baseline hemoglobin A1c >8% had a larger relative risk reduction (HR 0.63; 95% CI 0.52–0.76) than those with HbA1c ≤8% (HR 0.93; 95% CI 0.79–1.11). The interaction P value was .0027, indicating a statistically significant heterogeneity of treatment effect by baseline HbA1c.
Baseline albuminuria: Participants with urine albumin-to-creatinine ratio (UACR) ≥2000 mg/g experienced a greater relative benefit (HR 0.53; 95% CI 0.39–0.72) compared with those with UACR <100 mg/g (HR 0.90; 95% CI 0.58–1.39). The interaction P value reported was .0367.
These subgroup results suggest larger relative reductions in infection-related outcomes with semaglutide among patients with poorer baseline glycemic control and higher degrees of albuminuria.
Within this randomized, high-risk population of people with T2D and CKD, semaglutide 1.0 mg once weekly reduced the prespecified composite of infection SAE, hospitalization for infection, or all-cause death (HR 0.79). Semaglutide also yielded lower rates of infection SAEs, hospitalization due to infection, and both COVID-19 adverse events and COVID-19 SAEs.
The greater relative benefits seen in subgroups with HbA1c >8% and with very high baseline albuminuria (UACR ≥2000 mg/g) indicate that patients with worse glycemic control and greater albuminuria may derive larger reductions in infection-related outcomes. The authors conclude these findings support potential clinical benefits of semaglutide beyond kidney, cardiovascular, and metabolic outcomes in high-risk patients with T2D and CKD.
Clinicians treating patients with T2D and CKD may consider these findings when weighing the broader benefits of GLP-1 receptor agonist therapy. The results suggest a potential role for semaglutide in reducing serious infection events, including COVID-19–related complications, particularly among patients with more advanced albuminuria or poorer glycemic control.
The abstract provides key hazard ratios, event rates for several endpoints, and subgroup interaction P values. However, the abstract does not report certain details that clinicians and researchers may consider important, including:
These unreported details were not included in the source abstract and would require consultation of the full-text article for complete appraisal.
In the prespecified analysis reported from the FLOW randomized clinical trial, once-weekly semaglutide 1.0 mg reduced the risk of a composite of infection SAE, hospitalization for infection, or all-cause death, and lowered rates of infection SAEs, hospitalizations for infection, and COVID-19 events. Benefits appeared larger in participants with baseline HbA1c >8% and with very high albuminuria (UACR ≥2000 mg/g). The abstract authors interpret these results as evidence that semaglutide may provide infection-related clinical benefits in addition to established kidney, cardiovascular, and metabolic effects in high-risk patients with T2D and CKD.
For full methodological detail, absolute event counts, follow-up duration, and additional subgroup or sensitivity analyses, readers should consult the full published article.