DPP-4 inhibitors in current diabetes care: their foundational role in treating to target

Despite major advances in glucose-lowering therapies, a substantial proportion of individuals with type 2 diabetes (T2DM) do not achieve recommended glycemic targets, maintaining a high risk of microvascular and macrovascular complications. While current guidelines prioritize agents with proven cardiovascular and renal benefits (treat-to-benefit), optimal glycemic control (treat-to-target) remains a cornerstone of diabetes management. This review supports an integrated therapeutic framework in which both strategies are pursued in parallel and examines the role of dipeptidyl peptidase-4 inhibitors (DPP-4is) within this context. DPP-4is provide clinically meaningful HbA1c reductions, approximately 0.6-1.1%, with a low risk of hypoglycemia, weight neutrality, and a favorable tolerability profile. Cardiovascular outcome trials have established their cardiovascular safety, and they are particularly suitable as add-on treatment to metformin, SGLT-2 inhibitors, or insulin, enabling safe intensification to achieve glycemic targets while maintaining cardiorenal-protective regimens. DPP-4is tolerability makes them specifically indicated for older patients. In contemporary diabetes care, DPP-4is-particularly sitagliptin-remain a versatile option bridging treat-to-target and treat-to-benefit paradigms to support comprehensive cardiovascular-kidney-metabolic (CKM) reduction in T2DM.