Effectiveness of sodium-glucose cotransporter type 2 inhibitors and urate-lowering agents in patients with gout: data from a single-center specialised clinic

 

J. Doménech, I. García, C. Rodríguez, P. Riesgo, O. Moreno-Pérez, M. Andrés.

 

Affiliation(s):

Alicante General University Hospital

 

 

Background: Sodium-glucose cotransporter type 2 inhibitors (SGLT2I) have proved substantial benefits in diabetes mellitus (DM), heart failure (HF), and kidney disease (KD). In pivotal trials, SGLT2Is reduced serum urate (SU) levels, but the clinical evidence in patients with gout under other urate-lowering drugs (ULD) is scarce [PMID 38472344].

Objectives: To evaluate the urate outcomes in patients with gout treated with SGLT2I and ULD in clinical practice.

Methods: Retrospective, single-center observational study, enrolling patients with gout from a crystal arthritis specialized clinic. We selected those receiving combined treatment with ULD and SGLT2I, regardless of the indication. Cases with no serum urate (SU) levels available in the 6 months before and after combined treatment or starting renal replacement therapy were excluded. The main variable of the study was SU level pre- and post-SGLT2I (mg/dL) statistically analized using Wilcoxon test as a non parametric continuous variable. As secondary variables, we measured the percentage achievement of SU target (<6 mg/dL or <5 mg/dL), the required allopurinol dose (mg) and pre-estimated dose according to the Easy-Allo tool (mg) [PMID 38359899]. Other relevant laboratory variables were also collected.

Results: Forty-six patients were included: median age 76 years (IQR 15.25), 82.6% men, with high comorbidity (91.1% with DM, 58.7% with KD,  45.7% with HF) and 10 years (IQR 20) of gout duration. As ULD, 66.7% (n=30) of patients were treated with allopurinol, 28.9% (n=13) with febuxostat, and 4.4% (n=2) with benzbromarone. Regarding the SGLT2I, 58.7% (n=27) received dapagliflozin, 30.4% (n=14) empagliflozin, and 10.9% (n=5) canagliflozin. ULD were initially prescribed in 81.4% (n=35), while SGLT2I in the remaining 18.6% (n=8).

The target of SU <6 mg/dL was achieved in 97.7% (95%CI 88.2-99.6%) of the patients, while 81.4% also reached <5 mg/dL (95%CI 65.5-88.9%). The achievement of the <5 mg/dL target was unrelated to the first prescribed medication (ULD 81.3% vs SGLT2I 87.5%, p=1.000) or the type of xanthine-oxidase inhibitor (allopurinol 79.3% vs febuxostat 91.7%, p=0.651).

The start of SGLT2I showed a median SU reduction of 0.85 mg/dL (IQR 3.02, p=0.001 for the before-after comparison) [Figure 1]. The SU reduction was observed regardless of being already on ULD (median 0.80, IQR 2.90, p=0.021) or not (median 3.00, IQR 6.95, p=0.018) or of changes in diuretics use (p=0.692).

No significant differences in allopurinol dose were found pre- and post-SGLT2I use but with a trend toward a lower dosage than pre-estimated by the Easy-Allo tool.
The use of SGLT2I showed significant reductions in fasting glucose, HbA1c, and C-reactive protein levels, increased urine glucose excretion, and no differences in urine albumin and glomerular filtration rate. We detected a significant reduction in diuretics use pre- and post-SGLT2I (60.9% vs 54.3%, p<0.001) Figure 1.

Conclusions: The combination of SGLT2I and ULD in patients with gout in clinical practice achieved significant SU level reductions and targets of SU <6 mg/dL and <5 mg/dL. A trend towards a lower dosage requirement of allopurinol was noted, along with a reduced use of diuretics. These promising results require confirmation by further intervention studies.

References:
Yokose C, McCormick N, Abhishek A, et al. The clinical benefits of sodium-glucosecotransporter type 2 inhibitors in people with gout. Nat Rev Rheumatol. 2024;20:216-231. doi: 10.1038/s41584-024-01092-x.

Wright DFB, Hishe HZ, Stocker SL, et al. The development and evaluation of dose-prediction tools for allopurinol therapy (Easy-Allo tools). Br J Clin Pharmacol. 2024;90(5):1268-1279. doi:10.1111/bcp.16005.