Do Gliflozins Affect the Need to Use Diuretics?
Sodium-glucose cotransporter 2 inhibitors (SGLT2i, i.e., gliflozins) have advanced from their initial role in reducing hyperglycemia in the treatment of type 2 diabetes mellitus (DM2) to antidiabetics with proven cardioprotective effects and additional indications for patients with heart failure or chronic kidney disease. Last year, the CHAMPION cohort study was published, which investigated the impact of empagliflozin use on diuretic prescribing and mid-term laboratory results in patients concurrently treated with diuretics.
Introduction
SGLT2i exhibit diuretic effects, yet this effect has not been extensively studied in specialized trials. Moreover, there is minimal published data on the effects of adding SGLT2i to conventional diuretic therapy. According to data from the EMPA-REG study, the antihypertensive effects of SGLT2i decrease with declining renal function, which may indicate weaker diuretic efficacy in patients with kidney impairment.
The benefits of SGLT2i are as diverse as their mechanism of action – they are effective in all stages of DM2, associated with a low risk of hypoglycemia, contribute to weight loss like traditional diuretics but without the risk of tachycardia or gout flare-ups (Sica et al., J Clin Hypertens 2011), and significantly reduce uric acid levels (e.g., empagliflozin in the study by Zinman et al., NEJM 2015).
The study described below evaluated how empagliflozin administration affects concurrent diuretic prescriptions and certain laboratory parameters.
Study Methodology
A retrospective cohort study included 1,189 patients treated with empagliflozin, with one-third (n = 439) concurrently prescribed diuretics, forming the intervention group, while the remaining two-thirds (n = 750) constituted the control group. The primary endpoint was the impact of empagliflozin use on diuretic prescribing (i.e., unchanged, discontinued, reduced, increased). Secondary endpoints included changes in body weight, levels of glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, blood pressure, and electrolytes after 90 and 180 days. Subjects without diuretics were matched with those using diuretics based on the propensity score. The average differences between groups were determined using the t-test, and within groups using the paired t-test.
Results
Among the 439 patients in the intervention group, 118 experienced changes in their diuretic regimen, specifically 131 changes: in 109 cases (83.2%) diuretics were discontinued, in 13 cases (9.92%) doses were reduced, and in 9 cases (6.87%) doses were increased. The median dose of loop diuretics equivalent to furosemide decreased from 50.62 to 43.13 mg after initiating empagliflozin (p < 0.001).
For the entire patient population, there was a reduction in body weight (p = 0.01), HbA1c levels decreased (p < 0.001), hemoglobin levels increased (p < 0.001), hematocrit increased (p < 0.001), and magnesium levels increased (p < 0.001). A decline in eGFR was also observed (p < 0.001).
In the group using empagliflozin plus diuretics, the average body weight decreased significantly more than in the empagliflozin-only group (p < 0.001). Other secondary endpoints were not affected by concurrent diuretic use.
Conclusion
This study showed that SGLT2i use may lead to a reduced need for concurrent diuretic administration. After initiating empagliflozin, the prescription of diuretics was discontinued in approximately a quarter of the patients.
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Source: Patil T., Halsey E., Kaur A. et al. Changes in diuretic medication prescribing and surrogate laboratory parameters after initiating empagliflozin in veterans (CHAMPION Cohort Study). Clin Drug Invest 2023 Jan; 43 (1): 61–74, doi: 10.1007/s40261-022-01226-7.
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