Study links drugs for type 2 diabetes to lower death risk in Fabry disease
SGLT2 inhibitors may also reduce risk of heart attack in these patients
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Treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i), a medication used for type 2 diabetes, may reduce the risk of death and heart attacks in people with Fabry disease, according to a new analysis.
“In this real-world cohort of patients with [Fabry disease], exposure to [SGLT2i] was associated with a lower risk of … all-cause mortality, with additional favourable signals for [heart attack] over longer follow-up,” researchers wrote.
Based on their findings, researchers called for further studies into how SGLT2i may affect outcomes in people living with Fabry disease.
“These findings should be considered hypothesis-generating and warrant confirmation in prospective studies and dedicated Fabry disease cohorts or registries,” scientists wrote.
The study, “SGLT2 Inhibitors and Cardiovascular Outcomes in Patients With Fabry Disease: Observations From a Federated Research Network,” was published in Diabetes, Obesity and Metabolism.
Team analyzed data from thousands of patients
Fabry disease is a genetic disorder in which the body is unable to break down certain fatty molecules, which build up to toxic levels in cells and damage organs. The kidneys and heart are commonly impacted in Fabry.
SGLT2i are a group of medications that are used to treat type 2 diabetes. These medications reduce blood sugar by increasing the amount of sugar the kidneys remove from the blood and filter into the urine.
Some research suggests that SGLT2i may improve outcomes in people with heart disease and/or kidney disease. Since heart and kidney issues are common among people with Fabry, an international team of scientists wondered whether SGLT2i may impact outcomes in Fabry disease.
The team analyzed data from the TriNetX Global Collaborative Network, a real-world research platform that contains de-identified data from electronic medical records at centers worldwide. From the data, the researchers identified 14,940 people with a diagnosis of Fabry. Just over 1,000 of them had ever taken SGLT2i.
Risk of death, heart attack lower at 2 and 5 years
The researchers found that patients who’d taken SGLT2i were generally older, with more co-occurring health issues and worse kidney health markers. To account for these underlying differences, the team used a statistical process called propensity score matching. In essence, the team identified matched sets of patients with similar clinical profiles, differing only in SGLT2i use.
The propensity score-matched analysis ultimately included 732 Fabry patients who had taken SGLT2i and an equal number who had not. Using statistical models, the researchers compared the risk of a composite endpoint that included death from any cause, heart attack, or acute/acute-on-chronic heart failure.
Results showed that, at two years, the risk of this composite outcome was significantly lower — by approximately 39% — in patients on SGLT2i. Patients on SGLT2i also had a lower risk of the composite outcome at five years, by roughly 44%.
More granular analyses showed that the risk of all-cause death was significantly reduced among patients on SGLT2i, by 44% after two years and 38% at five years. The risk of heart attack at five years was also significantly reduced among patients on SGLT2i, by about 47%.Â
Among patients with [Fabry disease], SGLT2i-exposed patients had a lower risk of the composite outcome and all-cause death, as well as [heart attack] at [five] years compared with non-exposed patients.
Additional analyses examining outcomes at three or six years showed broadly similar results, and exploratory tests indicated that the impact of SGLT2i was consistent regardless of patients’ age or biological sex.
“Among patients with [Fabry disease], SGLT2i-exposed patients had a lower risk of the composite outcome and all-cause death, as well as [heart attack] at [five] years compared with non-exposed patients. These associations were already evident at [two] years and remained overall consistent across sensitivity analyses using alternative follow-up windows of [three] and [six] years, supporting the robustness of the main findings over time,” the researchers concluded.
The researchers noted that kidney health outcomes did not differ significantly between patients who were or weren’t taking SGLT2i.
“Therefore, the present findings do not provide evidence of a renal benefit associated with SGLT2i exposure,” they wrote.
The scientists highlighted several limitations in this analysis, including reliance on health record data that may be incomplete or inaccurate. Additionally, they noted that most patients in the propensity score-matched analysis had type 2 diabetes in addition to Fabry disease. Since SGLT2i treatment has well-established benefits for type 2 diabetes, it’s unclear whether the differences in this study reflect a specific effect of these medications on Fabry itself. As such, the scientists said more studies are warranted.
“These considerations warrant cautious interpretation of the findings and limit both their generalizability and [ability to make conclusions about cause and effect],” the scientists wrote.
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