Optimal management of type 2 diabetes often requires intensification beyond dual therapy. A study at EASD 2025 evaluated early quadruple combination therapy, including a thiazolidinedione (lobeglitazone) and an SGLT2 inhibitor (empagliflozin), versus conventional stepwise escalation in patients inadequately controlled on metformin and a dipeptidyl peptidase 4 inhibitor.

In this randomised, open-label study, 158 participants were assigned to early quadruple therapy or stepwise escalation starting with either lobeglitazone or empagliflozin. Over 112 weeks, the early quadruple therapy group achieved a larger reduction in HbA1C (from 7.47% to 6.37% vs. 6.55%; P = 0.031) and greater improvement in insulin resistance measured by HOMA-IR. Body weight remained stable in the early quadruple group, while it decreased in the stepwise escalation group starting with empagliflozin. Liver fat and stiffness improved similarly across groups.

All treatments were well-tolerated, with no hypoglycemia and rare discontinuations due to adverse events. These findings suggest that early quadruple therapy can safely enhance glycaemic control and metabolic outcomes in patients insufficiently managed with dual therapy.