Changes in Metabolic and Blood Pressure Outcomes With Semaglutide Across Chronic Kidney Disease Stages: A Post Hoc Analysis of the FLOW Trial

ABSTRACT Aims To assess changes in glycated haemoglobin (HbA1c), body weight, and systolic/diastolic blood pressure (SBP/DBP) by chronic kidney disease (CKD) and albuminuria categories in a post hoc analysis of FLOW, an international, double‐blind, randomized, phase 3b clinical trial of adults with CKD and Type 2 diabetes (T2D). Materials and Methods We evaluated the effect of semaglutide 1.0 mg versus placebo (in addition to standard of care) on changes in HbA1c, body weight, SBP, and DBP from baseline to Week 104 stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 60, ≥ 45 to < 60, ≥ 30 to < 45, < 30 mL/min/1.73 m 2 ) and urine albumin‐to‐creatinine ratio (UACR; < 30, 30 to < 300, and ≥ 300 mg/g). Outcomes were analysed using analysis of covariance with baseline eGFR/UACR as covariates and an interaction term for treatment group by eGFR/UACR categories. We calculated the estimated treatment difference (ETD) between the semaglutide and placebo groups. Results FLOW included 3533 participants. Compared with participants assigned placebo, those assigned semaglutide had greater reductions in HbA1c (ETD range across eGFR/UACR groups: −0.7% to −1.0%; all p < 0.0001) and body weight (ETD: −2.5 kg to −4.6 kg; all p < 0.0001 except UACR < 30) from baseline to Week 104. Participants with lower baseline eGFR/higher UACR categories treated with semaglutide also had greater improvements in SBP than those receiving placebo. In interaction analyses, the treatment effect did not differ significantly by baseline eGFR/UACR for any of the outcomes. Conclusions Semaglutide improves glycaemic control and weight, regardless of baseline eGFR or UACR, and SBP in lower eGFR/higher UACR categories.