"Dapagliflozin vs Dapagliflozin-Finerenone for Albuminuria in CKD With Type 2 Diabetes"

Chronic kidney disease (CKD) is a common and serious complication of type 2 diabetes mellitus (T2DM), contributing significantly to morbidity, mortality, and cardiovascular risk. It often progresses silently and is characterized by persistent albuminuria and declining renal function. Globally, approximately 27% of individuals with T2DM are affected by CKD, with regional variations reflecting differences in healthcare access, comorbidities, and socioeconomic factors. In Bangladesh, the prevalence is notably high, reaching around 34.5% in hospital-based studies, highlighting a major public health concern.

CKD in T2DM is strongly associated with increased cardiovascular morbidity and premature mortality, with cardiovascular disease being the leading cause of death in this population. Despite standard therapies, many patients continue to progress to end-stage kidney disease, emphasizing the need for improved treatment strategies.

Albuminuria is a key marker of glomerular injury and a strong predictor of CKD progression and cardiovascular outcomes. Reduction in urinary albumin-to-creatinine ratio (UACR) is therefore an important therapeutic target and a validated surrogate endpoint in clinical trials. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs) have demonstrated significant benefits in reducing albuminuria through complementary mechanisms, including improvement of tubuloglomerular feedback and reduction of inflammation and fibrosis.

Dapagliflozin, a selective SGLT2 inhibitor, has shown robust renoprotective and cardioprotective effects, including reduction in albuminuria and slowing CKD progression, as demonstrated in major trials such as DAPA-CKD. Finerenone, a non-steroidal MRA, offers enhanced receptor selectivity with anti-inflammatory and anti-fibrotic effects, along with a lower risk of hyperkalemia compared to traditional MRAs. Large trials such as FIDELIO-DKD and FIGARO-DKD have confirmed its efficacy in reducing renal and cardiovascular outcomes.

Emerging evidence suggests that combining SGLT2 inhibitors with finerenone may provide additive or synergistic benefits, particularly in reducing albuminuria and improving cardiovascular outcomes. Additionally, SGLT2 inhibitors may mitigate the risk of hyperkalemia associated with MRAs, improving the safety profile of combination therapy.

Although current guidelines recommend both drug classes in CKD associated with T2DM, direct comparative evidence between SGLT2 inhibitor monotherapy and combination therapy with finerenone remains limited, especially in South Asian populations. Variations in genetics, diet, and healthcare access further necessitate region-specific research.

This study aims to evaluate the efficacy and safety of dapagliflozin alone versus dapagliflozin combined with finerenone in reducing albuminuria among Bangladeshi patients with CKD and T2DM. The findings may help optimize treatment strategies and improve renal outcomes in this high-risk population.

• Number of participants with 30% or more eGFR fall from baseline to follow-up [Time frame: eGFR is measured at baseline, 4 weeks, and 8 weeks in dapagliflozin-finerenone combination group and the dapagliflozin-alone group and number of paricipants with 30%or more eGFR fall is measured in both groups and between groups]
• proportion of patients achieving at least 30% reduction in urinary albumin-to-creatinine ratio from baseline to 8 weeks [Time frame: urinary albumin-to-creatinine ratio reduction is measured at 4 weeks & 8 weeks in the dapagliflozin-finerenone combination group and the dapagliflozin-alone group and change of urinary albumin-to-creatinine ratio reduction is between group]
• frequency and pattern of adverse events from baseline to follow-up [Time frame: adverse events are evaluated at 4 weeks and 8 weeks in the dapagliflozin-finerenone combination group and the dapagliflozin-alone group and and compare between groups.]
• Number of participants with hyperkalemia from baseline to follow up [Time frame: Serum potassium is measured at baseline, 4 weeks and 8 weeks in dapagliflozin group and dapagliflozin- finerenone combination group, and number of participants with hyperkalemia is measured in both groups and between groups.]