Mohmed Sohel Shaikh, Suraj Tripathi, Chandra Bhanu Tripathi, Prashant M Parmar, Nilesh Patil, Hitesha H Trivedi
Introduction Type 2 diabetes mellitus (T2DM) often requires combination therapy when metformin alone fails to achieve adequate glycemic control. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and glimepiride, a sulfonylurea, are commonly prescribed as add-on therapies. This study compared their efficacy and safety in patients with inadequately controlled T2DM. Methods A nonrandomized prospective observational comparative study was conducted at a tertiary care teaching hospital between April and November 2024. A total of 170 adults with inadequately controlled T2DM receiving metformin (1000 mg) were allocated to receive either dapagliflozin (10 mg) (n=85) or glimepiride (2 mg) (n=85) and were followed for 24 weeks. Primary outcomes included changes in glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and postprandial blood sugar (PPBS). Secondary outcomes included body weight, blood pressure, and adverse events. Results Both treatment groups demonstrated significant improvements in glycemic control over 24 weeks. At study completion, HbA1c was significantly lower in the dapagliflozin group than in the glimepiride group (7.60±0.64% vs. 8.00±0.68%; p=0.01). Glimepiride produced a greater reduction in FBS (101.82±20.65 vs. 115.98±15.09 mg/dL; p<0.001), while PPBS was comparable between groups (p=0.45). Dapagliflozin resulted in significant weight loss and reductions in systolic and diastolic blood pressure, whereas glimepiride was associated with weight gain. Overall, adverse events were more frequent with dapagliflozin, primarily polyuria and genital infections, while hypoglycemia and tremors occurred more frequently with glimepiride. Conclusions Both dapagliflozin and glimepiride were effective as add-on therapy to metformin in improving glycemic control. Dapagliflozin was associated with greater HbA1c reduction, weight loss, lower blood pressure, and a lower risk of hypoglycemia, whereas glimepiride achieved greater fasting glucose reduction. Treatment selection should be individualized based on patient characteristics, comorbidities, and therapeutic goals.