The algorithm outlines the evidence-based positioning and clinical use of DPP-4 inhibitors, particularly vildagliptin, in the pharmacologic management of Type 2 Diabetes Mellitus (T2DM), aligned with the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and World Health Organization (WHO) 2024–2025 recommendations. Management begins with lifestyle modification combined with metformin as first-line therapy. Glycaemic response is reassessed after approximately three months. If HbA1c remains above target, treatment intensification is guided by comorbidities, treatment priorities, and patient-specific factors.
In patients with established atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD), GLP-1 receptor agonists or SGLT2 inhibitors are prioritized as second-line agents. DPP-4 inhibitors are generally reserved as third-line therapy when these preferred agents are contraindicated, not tolerated, or unsuitable. In individuals without major cardiorenal disease, DPP-4 inhibitors may be considered for moderate glycaemic reduction, particularly when minimizing hypoglycaemia risk and avoiding weight gain are important clinical goals.
Vildagliptin provides modest HbA1c reduction (approximately 0.5–1.0%) with a favourable safety profile, including weight neutrality and low hypoglycaemia risk. It may be combined with metformin, insulin, or SGLT2 inhibitors, while continuation of metformin is encouraged when not contraindicated. Importantly, DPP-4 inhibitors should not be co-administered with GLP-1 receptor agonists due to lack of additional clinical benefit.
Overall, the algorithm shows DPP-4 inhibitors’ position in therapy sequencing: typically second-line when hypoglycaemia avoidance is prioritized, third-line when weight reduction strategies dominate treatment goals, and potentially fourth-line when cost considerations drive treatment selection.