Safety and Efficacy of Different Classes of Antidiabetic Agents as Add on Therapy to Metformin in Management of Uncontrolled Type-2 Diabetes Mellitus Patients

Objective: To compare the safety and efficacy of different classes of Antidiabetic Agents as add-on therapy to Metformin in patients with uncontrolled Type-2 Diabetes Mellitus (T2DM). Methods: A Prospective, Observational, Comparative and Multi-centric study was conducted on 1870 patients with uncontrolled T2DM at Sri Bhadrakali Clinic. Patients were grouped based on the class of Antidiabetic Agent added to Metformin. Glycemic control was assessed using Fasting Blood Sugar (FBS), Post Prandial Blood Sugar (PPBS), and Glycated Hemoglobin (HbA1c) before treatment and at 3 and 6monthspost treatment. Safety was evaluated based on reported Adverse Drug Reactions (ADRs), including Hypoglycaemia, Gastrointestinal disturbances, and Genitourinary infections. Results: Among dual therapy regimens, Metformin combined with SGLT-2 inhibitors and DPP-4 inhibitors demonstrated superior glycemic control, with a significant reduction in FBS, PPBS, and HbA1c levels (p<0.05). Triple therapy combinations, particularly metformin + sulfonylurea + DPP-4 inhibitor, showed enhanced efficacy but a higher incidence of hypoglycemia. SGLT-2 inhibitor combinations were associated with mild Genitourinary infections but had favourable weight and glycemic outcomes. DPP-4 inhibitors were better tolerated overall. Conclusion: DPP-4 and SGLT-2 inhibitors, when added to metformin, are effective and relatively safe options for the management of uncontrolled T2DM. Individualized therapy based on patient profile, comorbidities, and ADR risk can optimize glycemic outcomes and minimize complications.