Clinical Effectiveness and Safety of Gliclazide MR and Linagliptin Combination in the Management of Patients With T2DM and Chronic Kidney Disease (CKD) Switched From Glimepiride - a Real-World, Retrospective, Observational Study

Background: Type 2 diabetes (T2DM) patients are at high risk of developing to CKD and progressing to adverse outcomes vs Nondiabetics. The aim was to evaluate the effectiveness and safety of gliclazide MR switched from glimepiride in combination with linagliptin considering their associated potential benefits in albuminuria reduction and delaying progression of adverse renal outcomes in T2DM patients with kidney disease as shown in previous data. Methodology: The medical study database of the author’s hospital identified T2DM patients with stage 1–3 CKD with mean eGFR of 50.4 ± 8.56 ml/min/1.73 m2 and were inadequately controlled with glimepiride (mean dose 3.24mg) for the last 3 months. These patients were switched to gliclazide MR with appropriate equivalent dose while DPP-4 inhibitors like linagliptin (5 mg OD) (79%), sitagliptin (14%), vildagliptin (7%), were continued as background therapy. About 59.35% of subjects were on glimepiride 2 mg, 21.93% subjects on glimepiride 3 mg and 18.7% on glimepiride 4 mg. The gliclazide dose was up titrated by 30 mg every 15 days to achieve a target post-prandial glucose (PPG) ≤180 mg/dL. The average dose of gliclazide MR during the study was 44 mg; approximately two-thirds of patients 61% were on 60 mg, 22% on 90mg, and 7% on 30 mg. Patients were counselled to recognize the symptoms and record the hypoglycemic episodes. The statistical analysis included the analysis of changes in glycemic control, risk of hypoglycemia & renal function parameters. The patients were followed up for 24 weeks duration. Results: A total 218 eligible patients (110 female & 108 male) with CKD (stages 1–3) were included. The mean age, body weight, baseline HbA1c, FPG, PPG levels, mean eGFR, and UACR (urine albumin creatinine ratio) were 62.94 ± 8.72 years, 67.9 ± 9.33 kg, 8.51 ±0.81%, 148.53 ± 16.72, 202 ± 18.45 mg/dL, 50.49 ± 8.56 ml/min/1.73 m2 and 154.34 mg/g respectively. Gliclazide MR was initiated substituting glimepiride with appropriate dosing determined by the physician. Two subjects discontinued the therapy due to intolerability. At 24 weeks follow up, HbA1c, FPG, PPG level was reduced by -0.63, -10.33, -30.04%, respectively (p< 0.001). There was a significant reduction in events of overall hypoglycemia (22.25%). Improvement in renal function with respect to eGFR level (+1.77 ml/min/1.73 m2) and albuminuria reduction (-45.56 mg/g) were also observed in patients. Conclusion: This study demonstrates the clinical effectiveness and safety of gliclazide MR with the combination of DPP-4is like linagliptin as an alternate option to glimepiride in diabetes patients with chronic kidney disease.