"In this large real-world analysis, GLP-1 receptor agonists were associated with a substantial reduction in the risk of right heart failure in patients with PAH. While mortality outcomes were similar, the marked improvement in right ventricular performance suggests a potential new therapeutic direction for the management of this disease," commented the lead author, Saud Alawad from West Virginia University in Morgantown, in a statement from the scientific society.
The two classes of antidiabetic drugs studied have demonstrated cardiovascular benefits in patients with type 2 diabetes and may also have effects on pulmonary vascular function. GLP-1 analogues in particular may limit PAH by suppressing autophagic and mitochondrial stress in pulmonary smooth muscles, while SGLT2 inhibitors appear to improve cardiorespiratory function.
To compare the effects of these two therapeutic classes, the researchers used the TriNetX database, identifying adult patients diagnosed with PAH between 2013 and 2021.
Two cohorts were established, one of 1,611 patients using GLP-1 analogues without using SGLT-2 inhibitors - or gliflozins - and the other of 2,124 patients treated with gliflozins but not taking GLP-1 analogues, with an average follow-up of 713 days and 557 days respectively.
After propensity score matching, taking into account patients' demographic characteristics, cardiovascular and respiratory conditions, endocrine disorders, heart and PAH medications, body mass index (BMI), glycated haemoglobin levels, and BNP levels, the analysis of data from 1,121 pairs of patients showed a relative risk of all-cause mortality of 0.906, which was statistically non-significant.
The risk of respiratory failure was also similar between the two groups.
However, GLP-1 analogues in patients with PAH were associated with a statistically significant reduction in the risk of right heart failure, by 53.6%, compared to gliflozins.
The researchers also reported that BNP (B-type natriuretic peptide, a marker of heart health) levels were significantly lower in patients treated with GLP-1 analogues compared to those taking SGLT-2 inhibitors, at 338 pg/mL and 829 pg/mL respectively, suggesting potential variations between these two therapeutic classes on cardiac stress.
These results highlight the need for randomised controlled clinical trials to validate these observations and directly compare the benefit-risk profile of these two families of antidiabetic drugs in the management of PAH, the researchers conclude.
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