Subsequent studies revealed that certain glucose-lowering agents, particularly thiazolidinedione (pioglitazone) and DPP4 inhibitors (especially saxagliptin), could paradoxically increase the risk of heart failure events despite effective glycemic control [43,44,45], whereas other antidiabetic drugs, such as metformin, insulin, and sulfonylureas are largely neutral regarding HF outcomes. Here, INS is linked to heart failure.