GLP-1 agonists may reduce heart failure risk in people diabetes and plasma cell disorder

A woman taking a GLP1-agonist. Getty/coldsnowstorm

By Olivia Bowthorpe

Glucagon-like peptide-1 (GLP-1) receptor agonists may have a “primary prevention role” in people with monoclonal gammopathy of undetermined significance (MGUS) and type 2 diabetes, a study has found.

A new international study, from the Yale School of Medicine in Connecticut, found significantly lower rates of major adverse cardiovascular and cerebrovascular events or all-cause mortality in patients with both conditions who were receiving the drugs.¹

Writing in JAMA Network Open, the researchers explained that MGUS, which affects about 3% of people over 50 years, and more than 7% of those over 85, normally shows no symptoms.

However, it involves abnormal plasma cells and is believed to be a marker for raised cardiovascular risk, as well as a precursor to multiple myeloma or other blood disorders.

Led by Dr Michael Nanna, assistant professor of internal medicine, the team analysed data on 4,871 adults with MGUS plus type 2 diabetes from the TriNetX Global Database.

They compared the outcomes of 460 patients who were prescribed GLP-1s to the same number who were not. The average body mass index (BMI) in both groups was 36, and none had experienced a prior cardiovascular event, such as heart failure, coronary disease, or stroke.

Over a mean follow-up period of around three years, those in the GLP-1 group showed a 25% lower rate of major adverse cardiovascular and cerebrovascular events or all-cause mortality.

Individually, the rate of all-cause mortality was 43% lower, new-onset heart failure 31% lower, decompensated heart failure 40% lower, and acute kidney injury or end-stage kidney disease 27% lower.

The results "suggest the potential of GLP-1 receptor agonists for primary prevention of major adverse cardiovascular and cerebrovascular events," and "warrant further investigation in prospective randomised trials", the authors reported.

Explaining the potential mechanisms behind the benefit, they said that obesity exacerbates MGUS pathways, as well as increases the chronic inflammation that may contribute to cardiovascular and renal damage.

They called for further studies to examine whether the benefits of GLP-1 receptor agonists in MGUS are due to a novel interaction with MGUS, or to known cardiovascular-kidney pathway mechanisms.

Future studies should also include a higher proportion of participants without an elevated BMI, to increase generalisability, they added.

Reference:

1. Chi KY, Song J, et al. GLP-1 RA Use and Major Adverse Cardiovascular Events in Patients With Monoclonal Gammopathy of Undetermined Significance JAMA Netw Open Online 2025 [full text]

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