SGLT-2s
Elizabeth Briand
A recent study in examined the use of SGLT-2 inhibitors in reducing BP in patients with hypertension, including those who have been experiencing apparent treatment-resistant hypertension and proteinuria.
SGLT-2 inhibitors were initially approved for lowering blood glucose levels in patients with T2D. Some of them are also approved to reduce the risk of hospitalization due to heart failure in patients with or without T2D and for slowing the progression of chronic kidney disease. In addition to these uses, they have demonstrated a BP reduction benefit.
Examining SGLT-2 inhibitors and BP reduction
Jaejin An, PhD, is a pharmacoepidemiologist who serves as an outcomes researcher with the Kaiser Permanente Southern California Department of Research and Evaluation and led the SGLT-2 inhibitors study.
“Our team was curious about the real-world impact of [SGLT-2 inhibitors] use on blood pressure in patients with hypertension who received routine clinical care in Kaiser Permanente Southern California,” she said. “Often, these patients take multiple medications to lower their blood pressure, and some struggle with resistant hypertension.”
The goal was to dive deeper into the possibilities of SGLT-2 inhibitors. “Beyond the proven clinical benefits of [SGLT-2 inhibitors], we wanted to test the hypothesis that these medications could offer additional benefits for patients with treated hypertension,” said An. “If patients can reduce their current hypertension medications or control their blood pressure without increasing their medications, it would be a significant advantage from the patients’ perspective.”
The study used the EHRs of nearly 13,000 patients, aged 18 years or older, within the Kaiser Permanente Southern California system who had initiated SGLT-2 inhibitors use between 2013 and 2022 and were in treatment for hypertension.
Nearly 96% of the patients had T2D, and nearly 17% had heart failure. The study population included 3,774 patients with apparent treatment-resistant hypertension and 2,913 patients with proteinuria. The patients were followed until the end of SGLT-2 inhibitors exposure or up to 12 months, whichever occurred first.
Although the primary goal of the study was to survey outpatient BP change from before to after SGLT-2 inhibitors’ initiation, the study also looked at whether patient use of antihypertensive medications declined.
“Our study showed a mean reduction in systolic/diastolic blood pressure of 5.3/2.5 mm Hg among patients with treated hypertension, with many patients discontinuing one or more of their hypertension medications,” said An. “The blood pressure reduction was even greater among patients with resistant hypertension or proteinuria.”
The mean systolic and diastolic BP reductions were 6.2 and 2.8 mm Hg among patients with aTRH, and 6.1 and 2.9 mm Hg among patients with proteinuria. Researchers also observed weight loss, HbA1C reduction, and hematocrit increase among all three groups after starting SGLT-2 inhibitors.
As for the discontinuation in antihypertensive medications, their use decreased from 3.6 to 2.9 medications for patients with aTRH, from 2.6 to 2.2 for patients with proteinuria, and from 2.3 to 1.9 for all treated patients.
Because more than 70% of patients with T2D also have hypertension and often are coping with a high medication burden, the findings may be of particular relevance for this population.
Possible causes and future use
Although the study did not delve into the possible causes behind the observed BP reductions, An said they “believe that [SGLT-2 inhibitors] act similarly to diuretics by increasing the urinary excretion of both glucose and sodium. Other suggested mechanisms include weight loss, improvements in arterial stiffness, and reductions in sympathetic nervous system activity.”
For pharmacists, it is important that they be aware of the BP-lowering effects of SGLT-2 inhibitors and “be actively involved in medication therapy management and patient counseling,” said An. “The potential benefit of [SGLT-2 inhibitors] on medication burden in addition to clinical outcomes may be a consideration in future management strategies for hypertension‐related care.” ■