Comparative Effects of Dapagliflozin versus Linagliptin as Add-on to Metformin on Glycemic and Renal Outcomes: A 24-Week Non-Randomized Prospective Observational Cohort Study in Indian Patients with Type 2 Diabetes Mellitus and Stage 2-3a chronic kidney disease

Background: Diabetic nephropathy remains one of the leading causes of end-stage renal disease among individuals diagnosed with type 2 diabetes mellitus (T2DM). Achieving optimal glycaemic control plays a vital role in slowing the progression of diabetic kidney disease. However, real-world evidence directly comparing the impact of SGLT2 inhibitors versus DPP-4 inhibitors on kidney outcomes in Indian patients with diabetes is currently limited. This study evaluated the efficacy and safety profile of dapagliflozin in comparison with linagliptin, each added to background metformin therapy, with respect to glycemic control and renal parameters in patients presenting with uncontrolled T2DM and coexisting diabetic kidney disease. Methods: This 24-week, single-centre, non-randomized open-label prospective cohort study included 94 adult patients with uncontrolled T2DM (HbA1c 8.0–10%) and CKD stage 2-3a (eGFR 45–89 mL/min/1.73 m²). Based on treating physician’s clinical judgement, patients received either linagliptin 5 mg daily (n=47) or dapagliflozin 10 mg daily (n=47) in addition to ongoing metformin therapy. The primary outcome was the change in HbA1c at 24 weeks. Secondary outcomes included mean changes in eGFR, urinary albumin-to-creatinine ratio (uACR), and the proportion of patients achieving HbA1c <7%. Results: A total of 88 patients completed the study (6 lost to follow-up). Both treatment arms demonstrated significant reductions in HbA1c (linagliptin: –0.79%; dapagliflozin: –1.11%), fasting plasma glucose, and uACR at 24 weeks (p<0.05 within each group). The decline in eGFR was minimal and non-significant in both groups (–0.8 vs –1.0 mL/min/1.73 m², p=0.67). Adverse events were mild (26% vs 24%) and no serious adverse events occurred that required discontinuation of study medication. Conclusion: Dapagliflozin produced significantly greater reductions than linagliptin in urinary albumin-to-creatinine ratio, body weight, and serum uric acid (all p<0.05), while between-group differences in glycemic control (HbA1c, fasting plasma glucose) and eGFR did not reach statistical significance. Larger studies are required to confirm whether these observed trends translate into clinically meaningful benefits favouring SGLT2 inhibitors in this population. This pilot study confirms the feasibility of conducting future larger trials. No funding was received for this study.