BACKGROUND: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent =50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%.
OBJECTIVES: This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population.
METHODS: Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee.
RESULTS: A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment.
CONCLUSIONS: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153).
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Cardiology | |
| Endocrine | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
| Nephrology |  |
There is a theme here: SGLT2 inhibitors are good for heart failure, seemingly no matter what your comorbidities.
I am not sure my primary care physician colleagues already know this per se but even if the don't and this newly informs them, I don't think it is going to change practice very much. Semaglutide is already recommended for patients with DM and GFR less than 60, which is 79% of the enrolled population here.
In this large trial of GLP-1 agonists, patients in the intervention group were less likely to have both cardiovascular death and heart failure events. Useful information especially when dealing with patients who have high cardiovascular risk when you are trying to choose between this and an SG LT 2. It is useful to know it is also helpful in this group.
As an Internist working with patients with heart failure and CKD, I found this article very useful for every day clinical practice.
Encouraging data on benefits of GLP-1 analog in reducing heart failure events in patients with CKD/type 2 diabetes. Unfortunately, relatively few participants were on SGLT-2/MRA. This means the results may not be generalisable to real-world patients.
