PRAISE-HFrEF: Is it safe to use GLP1-receptor agonists in clinically severe HF?

A large observational study did not indicate that patients with clinically active heart failure (HF) are at an increased risk for hospitalisation for HF or mortality if they are treated with glucagon-like peptide-1 receptor agonists (GLP1-RA) at diabetes management dose.

“Some smaller studies suggest that the use of GLP1-RA may come with safety issues and risks in clinically advanced HF [1,2],” outlined Dr Varun Sundaram (University Hospitals Harrington Heart & Vascular Institute Cleveland, OH, USA). Now, the PRAISE-HFrEF trial included obese patients with type 2 diabetes who had active HFrEF within the last 12 months and with a new initiation of GLP1-RA, dipeptidyl peptidase-4 (DPP4) inhibitor, or sulfonylurea (SU) [3]. There were 1,228 participants in the GLP1-RA group and 1,501 participants in the active comparator group. The investigators applied inversed probability of treatment weighting to balance baseline characteristics. The main outcome was the time to first hospitalisation for HF or all-cause mortality.

There was no difference between participants on GLP1-RA or those on DPP4 inhibitor/SU for the time to first hospitalisation for HF or death from any cause (HR 0.97; 95% CI 0.85–1.23; P=0.74), suggesting that GLP1-RA may be equally safe to use in this population. “GLP1-RA may be the preferred option in patients with a BMI of 40 or higher, data from a subgroup analysis suggested,” added Dr Sundaram. Furthermore, weight loss was significantly larger among participants on GLP1-RA than those on DPP4 inhibitor/SU (14.1% vs 10.0%; P=0.0001).

“These findings should be considered hypothesis-generating results,” Dr Sundaram emphasised. “This was an observational study with unmeasured confounders and with limited generalisability of the results.” Since the data was retrieved from the Veteran Affairs health system, less than 4% of the included patients were women. Thus, although the data suggests that GLP1-RA is probably safe to use in patients with clinically severe HFrEF and obesity, there is a need for randomised studies (at weight loss dose) to confirm these findings.

1. Jorsel A, et al. Eur J Heart Failure. 2017;19(1):69-77.
2. Margulies KB, et al. JAMA. 2016;316(5):500-508.
3. Sundaram V, et al. PRAISE-HFrEF: glucagon-like peptide-1 receptor agonism in heart failure with reduced ejection fraction and obesity. Hottest trials and trial updates (1), Heart Failure 2025, 17–20 May, Belgrade, Serbia.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 20 May 202523 May 2025