Antidiabetic Therapies May Help Comorbid Pulmonary Hypertension in Veterans
Therapies associated with nearly 20% reduction in mortality risk for patients with pulmonary hypertension
Metabolic modulation may represent a viable therapeutic strategy in pulmonary hypertension (PH), report researchers from the Veterans Affairs Atlanta Healthcare System. Metformin and thiazolidinedione (TZD) were associated with significantly improved survival in their recent retrospective study of 41,670 veterans with PH and diabetes mellitus (DM). Insulin, on the other hand, was associated with increased mortality.
PH is a complex condition that may combine pulmonary vascular disease, heart disease, lung disease, and chronic thromboembolism. More than one-third of veterans with PH also have DM. Veterans are more likely than nonveterans to have chronic cardiopulmonary disease, which may make them particularly susceptible to PH. Moreover, those who served in Iraq and Afghanistan may have respiratory issues that predispose them to PH.
Another study from the same researchers assessed the influence of DM and weight, both potentially modifiable risk factors, on PH outcomes in 110,495 veterans. Veterans with PH survived an average of 3.9 years after PH diagnosis. Roughly one-third had DM, which increased risk of death by 31%. The analysis showed that lower weight and DM were strong risk factors for mortality in PH.
The most striking finding in the current study, according to the researchers, was a consistent reduction of about 20% in mortality risk associated with metformin and a similar association of 18% lower risk with TZD. The contrast with the 28% higher mortality with insulin “likely reflects fundamental differences” in how these medications influence cellular energy metabolism, they reported.
Interactions were observed between drug effects and both renal function and PH comorbidities, with metformin's protective effect enhanced in patients with lower estimated glomerular filtration rate but attenuated in those with lung disease. The associations remained “robust across multiple analytical approaches,” the researchers note.
Hemoglobin A1c was not associated with outcome, suggesting that these therapies' association with outcome may be irrespective of their glycemic effects. The researchers say this emphasizes the complex interplay between DM and PH pathobiology, known differences in mechanisms of action of antidiabetic medications, and potentially off target impacts of these metabolically active therapies.