Semaglutide helps prevent HF events, CV death in diabetic patients with CKD

Treatment with semaglutide can significantly lower the risk of time to first heart failure (HF) events or cardiovascular (CV) death in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), a recent study has shown.

In addition, the “beneficial effects of semaglutide were similar in participants with and without HF at baseline and across a range of clinically relevant subgroups over a 3.4-year mean follow-up,” the investigators said.

The coexistence of T2D and CKD heightens the risk for HF and death beyond that of either condition, they noted. [Diabetes Obes Metab 2020;22:9:1607-1618]

This study randomly allocated 3,533 patients to receive once-weekly subcutaneous semaglutide 1 mg or placebo. A composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death was the main outcome. 

The investigators gathered HF data, and an independent committee adjudicated CV death. Participants were followed over a median period of 3.4 years.

Of the participants, 342 (19.4 percent) in the semaglutide group and 336 (19.0 percent) in the placebo group presented with HF at baseline.

Semaglutide use increased time to first HF events or CV death (hazard ratio [HR], 0.73, 95 percent confidence interval [CI], 0.62–0.87; p=0.0005), HF events alone (HR, 0.73, 95 percent CI, 0.58–0.92; p=0.0068), and CV death alone (HR, 0.71, 95 percent CI, 0.56–0.89; p=0.0036).

Notably, the risk reduction for the composite HF outcome was observed in both patients with (HR, 0.73, 95 percent CI, 0.54–0.98; p=0.0338) and without (HR, 0.72, 95 percent CI, 0.58–0.89; p=0.0028) HF at baseline. [J Am Coll Cardiol 2024;84:1615-1628]

Furthermore, the risk of HF outcomes (HF events or CV death) was greater in participants with NYHA functional class III and those with HF reduced ejection fraction, regardless of treatment.

"[O]nce-weekly subcutaneous semaglutide 1.0 mg significantly reduced the risk of a composite outcome of HF events or CV death, and HF events alone, by 27 percent in a high-risk population with T2D and CKD,” the investigators said. “The risk of CV death alone was reduced by 29 percent.”

 Mechanisms

It remains unclear how semaglutide reduces HF outcomes in T2D patients with CKD, and it is not likely that the HF benefits can be credited to improvements in glycaemia alone, according to the investigators. [Diabetes Care 2010;33:4:721-727; N Engl J Med 2009;360:2:129-139]

Similar improvements in HF symptoms were noted in patients without T2D in the STEP-HRpEF trial and in those with T2D in the STEP-HFpEF DM. [N Engl J Med 2023;389:12:1069-1084; N Engl J Med 2024;390:15:1394-1407]

"It is possible that the weight loss observed with semaglutide underpins some of the improvements in HF,” the investigators said. 

“However, multiple lines of evidence indicate that there are additional, direct disease-modifying effects of semaglutide on the pathobiology of HF, which are likely independent of weight loss,” they added.