Semaglutide and HbA1c, weight and BP across CKD stages in FLOW post hoc analysis

The study

This is a post hoc analysis of FLOW, an international, double-blind, randomised, phase 3b trial in adults with chronic kidney disease (CKD) and type 2 diabetes (T2D). It was published in Diabetes, Obesity & Metabolism. FLOW included 3533 participants.

Participants received semaglutide 1.0 mg or placebo, in addition to standard of care. The authors looked at changes from baseline to Week 104 in HbA1c, body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP). They split the results by baseline eGFR (≥ 60, ≥ 45 to < 60, ≥ 30 to < 45, and < 30 mL/min/1.73 m2) and by baseline urine albumin-to-creatinine ratio (UACR; < 30, 30 to < 300, and ≥ 300 mg/g).

They used analysis of covariance, with an interaction term for treatment group by eGFR or UACR category. They report the estimated treatment difference (ETD) between semaglutide and placebo.

What they found

HbA1c. HbA1c fell more with semaglutide than with placebo in every eGFR and UACR group. The ETD ranged from -0.7% to -1.0% across groups (all p < 0.0001).

Body weight. Body weight also fell more with semaglutide. The ETD ranged from -2.5 kg to -4.6 kg. All p values were < 0.0001 except in the UACR < 30 mg/g group. The abstract does not give the result for that group.

Blood pressure. Participants with lower baseline eGFR or higher UACR who took semaglutide had greater improvements in SBP than those on placebo. The abstract does not report the SBP or DBP values, so the size of the effect cannot be stated here.

Interaction tests. The treatment effect did not differ significantly by baseline eGFR or UACR for any of the outcomes. The authors concluded that semaglutide improves glycaemic control and weight regardless of baseline eGFR or UACR, and improves SBP in lower eGFR and higher UACR categories.

How much weight to give it

The parent trial was randomised and double-blind, which is a strong design. This paper, however, is a post hoc analysis. The subgroups were not the main question of the trial, so the findings are best seen as supportive and hypothesis-generating.

The interaction tests were not significant. This means the abstract found no clear evidence that the effect differs between kidney categories. It does not prove the effect is the same in every group.

HbA1c, weight and blood pressure are surrogate outcomes. This analysis does not report kidney or cardiovascular events. The abstract does not report funding, adverse events, or confidence intervals for the ETDs, and it does not say how many participants were in each subgroup. The authors' conclusion about SBP is stated only for the lower eGFR and higher UACR categories, so it should not be extended to all patients.

For your clinic

These results suggest that metabolic benefits with semaglutide 1.0 mg were seen across a wide range of kidney function and albuminuria in people with T2D and CKD. This may help when you discuss expected glycaemic and weight effects in patients with reduced eGFR.

The analysis does not replace the main FLOW publication or current guidelines for decisions about kidney protection, safety and monitoring. Read the full paper, especially the subgroup sizes and safety data, before changing practice. Treatment choices should stay individual and follow your local guidance.