REAL LIFE EXPERIENCE AFTER 20 MONTHS USING SGLT2 INHIBITORS

Abstract Background and Aims Diabetic kidney disease (DKD) develops in almost half of diabetic patients and is the leading cause of chronic kidney disease (CKD). SGLT2 inhibitors (SGLT2i) have consistently shown to confer kidney protection in patients with type 2 diabetes (T2D). The recent KDIGO guidelines suggest their use as a first line medication along with metformin. After the study CREDENCE was published, in mid-2019, DKD patients at the Nephrology outpatient department of the Hospital of Braga were started on SGLT2i. We aimed at assessing these patients’ clinical and laboratory data after the introduction of the new drug. Method We collected data on age, gender, weight, blood pressure (BP) values, the use of renin-angiotension-aldosterone system inhibitors (RAASi), kidney function, glycated hemoglobin (HbA1c), glycosuria, proteinuria and albuminuria at baseline and during the two next patient assessments. Data was analyzed using SPSS®. Results Twenty-nine DKD patients who started SGLT2i between May 2019 and August 2020 were followed. Mean age was 71.2±13.5 years, 22 patients were male and their mean weight was 86.9±13.9 kg. They had had T2D for a mean of 15.9±10.3 years and a significant percent had end organ damage: 34% had diabetic retinopathy, 24% complaints suggestive of neuropathy, 51% had documented heart failure and 27% had cerebral vascular disease. Most were hypertensive with a mean BP of 156±19/83±11mmHg and 72.4% were taking RAASi. One third were treated with insulin. Most patients were started on canagliflozin (n=28) and one patient started empagliflozin. After starting the drug, patients were evaluated at a mean time of 141±55 days and had a second reevaluation at a mean time of 254±72 days. On the first evaluation they showed a significant reduction in the mean systolic BP to 140±15.1mmHg (p=0.001). Glycated hemoglobin decreased from a mean of 7.4±1.3% to 7.1±1.1% although this difference was not significant (p=0.4). Protein-creatinine urinary ratio was significantly reduced from a median value of 1.48 (IQR 0.24-1.85) to 0.93 (IQR 0.40-1.56). Mean serum creatinine increased significantly from baseline until the first evaluation at 1.96±0.49 to 2.27±0.66mg/dL (p=0.00) but remained stable on the second evaluation (2.29±0.79mg/dL). Seventy percent of the patients developed significant glycosuria (urinary concentration >500mg/dL) after starting SGLT2i. When asked about adherence, most non-glycosuric patients admitted not having started the drug. Conclusion Despite having a weak effect in the reduction of HbA1c, SGLT2i are an exciting drug for kidney protection in DKD. Patient adherence is easy to assess based on glycosuria. In our experience and based on this criterion drug compliance was acceptable (at least 70%) and we were able to reinforce instructions among non-compliant patients. Some of the benefits of SGLT2i were evident soon after they were started such as the improvement in BP and proteinuria. The initial increase in plasma creatinine was expected due to reduction in intraglomerular pressure and hyperfiltration and was noticeable only on the first assessment. We expect to continue SGLT2i use DKD patients.