Repurposing drugs may improve survival for people with sarcoidosis
Combo of blood pressure, diabetes meds found to reduce 5-year mortality
Combining angiotensin receptor blockers or ARBs — a type of medication used to lower blood pressure — with a class of diabetes medications called SGLT-2 inhibitors may help improve survival in adults with sarcoidosis, according to the findings of a new U.S. study.
Data showed that the simultaneous use of ARBs, which were previously reported to improve survival in sarcoidosis patients, and SGLT-2 inhibitors “was associated with a significant reduction in [five]-year all-cause mortality compared to ARBs alone,” the researchers wrote. The scientists noted that the five-year mortality rate among sarcoidosis patients is approximately 7%, “with pulmonary involvement as the leading cause of disease-related deaths.”
The team stressed that further studies are needed to validate these findings, but noted that the data showed significant benefits with the use of these repurposed diabetes drugs, particularly when combined with the blood pressure-reducing medications.
Overall, “our novel findings suggest that SGLT-2 inhibitors may confer survival benefits in sarcoidosis,” the team wrote.
The study, “Repurposing sodium glucose cotransporter-2 (SGLT-2) inhibitors in sarcoidosis: A potential strategy for reducing mortality,” was published in the journal Heart & Lung.
Sarcoidosis is an inflammatory disorder marked by abnormal clumps of immune cells, called granulomas, which can form in organs throughout the body, and lead to a wide range of symptoms.
Investigating the use of SGLT-2 inhibitors in sarcoidosis
While the exact causes of sarcoidosis remain unclear, “evidence suggests that the renin-angiotensin-aldosterone system (RAAS) plays a crucial role,” the researchers wrote.
The RAAS is a key regulator of blood pressure, increasing blood pressure when activated.
However, high levels of one of its components, angiotensin-converting enzyme or ACE, “contribute to granuloma formation and associated inflammation,” the researchers noted. This “[suggests] that RAAS signaling may be a potential target for therapeutic intervention,” the team wrote.
A previous study compared survival outcomes in sarcoidosis patients taking one of two types of RAAS-targeting medications — ARBs and ACE inhibitors — that are used to lower blood pressure. The results indicated that patients given ARBs had significantly better survival and fewer heart and lung complications compared with those on ACE inhibitors.
Building on that finding, the research team wondered if adding SGLT-2 inhibitors, a class of medications with anti-inflammatory and RAAS-modulatory effects, to ARB treatment would further improve survival in people with sarcoidosis.
SGLT-2 inhibitors were originally developed to help control blood sugar levels in people with diabetes, but they have also been approved to help protect the kidneys and heart in people with certain underlying conditions.
Using U.S. data from a global health record database, the scientists retrospectively analyzed electronic health records from 4,733 adults with sarcoidosis who were treated with both ARBs and SGLT-2 inhibitors. The team also examined an equal number of records for patients taking ARBs alone.
The two groups were carefully selected to be as similar as possible in terms of demographic factors, co-occurring health conditions, and use of immunosuppressive medications. The scientists conducted statistical analyses to compare survival outcomes between the two sets of patients.
“To our knowledge, our study is one of the first to explore the use of SGLT-2 inhibitors in a human sarcoidosis population,” the researchers wrote.
Chance of dying after 5 years reduced over 15% with combo therapy
The results showed that individuals given ARBs and SGLT-2 inhibitors had a significantly lower chance of dying after five years, by about 16.1%, compared with those on ARBs alone. Combining ARBs and SGLT-2 inhibitors was associated with a significant 3.2% reduction in the five-year death risk relative to ARBs alone.
More granular analyses looking at the chances of experiencing specific types of life-threatening complications, such as respiratory failure, heart failure, and acute kidney injury, generally did not find a statistically significant difference between the two groups.
Our novel findings suggest that [medications known as] SGLT-2 inhibitors may confer survival benefits in sarcoidosis that support [their] use beyond conventional roles in [blood sugar] control and [heart-kidney] protection.
“In this large, multi-institutional retrospective … study, we observed that among patients with sarcoidosis, the addition of SGLT-2 inhibitors to ARB therapy was associated with a significant reduction in our primary outcome of five-year all-cause mortality, compared to ARBs alone,” the scientists wrote. The team also noted that no differences were seen in secondary outcomes between the two groups.
“Our novel findings suggest that SGLT-2 inhibitors may confer survival benefits in sarcoidosis that support [their] use beyond conventional roles in [blood sugar] control and [heart-kidney] protection,” the researchers wrote.
The team noted, however, that because their analysis was based on data from electronic health records, there are likely additional factors influencing the data that couldn’t be fully accounted for in this study.
Studies following patients over time will be necessary to confirm these results and further explore the potential benefits of using ARBs in combination with SGLT-2 inhibitors for treating people with sarcoidosis, the scientists noted.
One area for research, per the team, is looking at synergy, or the combined effect of two or more treatments that may be greater than the sum of their individual effects.
“Future studies are warranted to validate these findings and explore underlying synergistic mechanisms of SGLT-2 inhibitors and ARBs, assessing the role of SGLT-2 inhibitors as potential disease-modifying agents in the management of sarcoidosis,” the researchers concluded.
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