TRANSLATIONAL AND CLINICAL MEDICINE - Georgian Medical Journal

Introduction

Currently, despite existing advances cardiovascular disease maintains a leading position (1)  in reducing  mortality among patients with type 2 diabetes mellitus (T2DM) (2). In patients with T2DM, diabetic nephropathy represents an equally serious complication, which itself serves as an independent predictive factor for cardiovascular complications and mortality (3,4). Empagliflozin is a sodium-glucose co-transporter 2 inhibitor (SGLT2i) used in T2DM, which has a positive impact on cardiovascular complications and renal outcomes, although the mechanisms remain not fully understood (4,5,6).It is important to study the influence of empagliflozin on renal filtration function in the setting of percutaneous coronary interventions (PTCA), which is a frequent procedure in ischemic heart disease (IHD) for myocardial revascularization. There is limited research on the use of empagliflozin in this patient category (5,6,7,8,9).

Methods

The study included 52 patients with IHD and T2DM (aged 57–75), all with chronic kidney disease (CKD) and scheduled for  coronary interventions. Patients were divided into two groups :Group I (Study group): 30 patients (15 men and 15 women) who were prescribed empagliflozin 10 mg daily one month prior to coronary intervention and continued for a total of 6 months.   Group II (Control group): 22 patients (11 men and 11 women) who continued their standard antidiabetic therapy with glomerular filtration rate  eGFR < 45 ml/min/1.73 m².
 The following parameters were measured: Peripheral blood glucose (hexokinase method), Glycated hemoglobin (HbA1c, enzymatic method), Daily urine protein (colorimetric method), Serum creatinine (Jaffe method),  Estimated glomerular filtration rate eGFR.( by CKD-EPI   ).Statistical significance was considered at p = 0.05.

Results and Discussion

The study was completed by 48 patients (28 in the study group and 19 in the control group). In the study group, 70% of patients had impaired carbohydrate metabolism,  in the control group-30% did. Empagliflozin therapy improved glycemic control in 75% of patients. No significant glycemic change occurred in the control group. Baseline blood glucose data  in the study group was 13.1 mmol/L, which decreased to 4.1 mmol/L after 6 months (p = 0.04).
In the control group, baseline glucose data was  8.45 mmol/L, decreasing to 7.4 mmol/L in 6 months (p = 0.05).  In the study group was able to improve glycemic control.   HbA1c in the study group decreased from 8% to 4% in 6 months (p = 0.05).
In the control group, HbA1c decreased from 7% to 6% (p = 0.19). Only 11% of the study group did not reach  the  target  glycemic levels. Baseline renal function was  evaluated by eGFR. In this regard there was no statistically  significant difference between the groups in the initial indicators.  One month after PTCA, a slight eGFR decline was observed, followed by stabilization and gradual improvement over the past 6 months, maintaining eGFR 58–60 ml/min/1.73m² (p = 0.56). Empagliflozin does not reduce functioning nephrons, which  indicates no direct impact on renal morphology (10–16).      It is worth noting today Empagliflozin’s effects on renal function in non-diabetic nephropathy, though studies remain limited (17). Empagliflozin reduces renal glucose reabsorption, increases urinary glucose excretion without causing hypoglycemia, improves glycemic control, and regulates renal dysfunction via increased filtration rate (18).The DECLARE trial, the largest study of T2DM and IHD patients, which   revealed  slowing down nephropathy progression, driving Forxiga (dapagliflozin) use (19,20).
DAPA-CKD showed favorable outcomes in T2DM and non-T2DM patients (21–24). Before Forxiga, there had been no breakthrough therapy in 20 years capable of slowing CKD progression in patients with or without T2DM (25,26). Thus, nephroprotection with empagliflozin is mediated by its hypoglycemic, anti-inflammatory, and pleiotropic effects (25–27).
The EMPA-REG OUTCOME trial showed that acute kidney injury occurred in 11% of patients with eGFR < 60 ml/min/1.73m² and 3.2% in those with eGFR > 60 ml/min/1.73m², but patients undergoing PTCA were not included in this trial (24,28).

Conclusion

Research shows that the effect of empagliflozin in T2DM patients undergoing elective coronary procedures is not well studied. In our study, patients with T2DM, CKD and IHD were included. Coronary interventions present a high risk for kidney injury, as contrast media used during angiography are strong predictors of renal damage. Adding empagliflozin to antidiabetic therapy resulted in a statistically significant HbA1c reduction in 87.3% of patients and achievement of target HbA1c levels. . Administering empagliflozin one month prior to myocardial revascularization serves as an effective compensatory approach in T2DM patients .Data from EMPA-REG OUTCOME showed  a slowdown in the progression of renal dysfunction with subsequent improvement (4). Research data indicate that SGLT2 inhibitors particularly empagliflozin, initially reduce eGFR, followed by stabilization and eventual improvement  (7,8,10). Their use  is associated with hypoglycemic and anti-inflammatory effects, regression of renal dysfunction, and improved kidney function (18,20).Empagliflozin 10 mg daily, initiated one month prior to revascularization and continued for 6 months, significantly improves glycemic control, slows renal dysfunction, and promotes eGFR improvement.

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