Clinical Efficacy of Quadruple Oral Therapy for Type 2 Diabetes in Real-World Practice: A Retrospective Observational Study

Introduction We aimed to evaluate the effectiveness of quadruple oral therapy in patients with inadequately controlled type 2 diabetes (T2D) with the use of three types of oral hypoglycemic agents. Methods Medical records of 318 patients with T2D who were prescribed quadruple therapy in the Asan Medical Center were reviewed. Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline were assessed. The regimens of quadruple oral therapy included the following: (1) thiazolidinedione (TZD) add-on to metformin (MET) + sulfonylurea (SU) + dipeptidyl peptidase 4 inhibitor (DPP4i), (2) sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on to MET + SU + DPP4i, and (3) DPP4i add-on to MET + SU + TZD. Results The TZD add-on significantly reduced HbA1c levels by 1.1% (from 9.0 +/- 1.1 to 7.9 +/- 1.1%,P < 0.001) and FPG levels by 41.4 mg/dL (from 188.9 +/- 45.9 to 147.4 +/- 51.3 mg/dL,P < 0.001). The SGLT2i add-on changed the mean HbA1c level from 8.9 +/- 1.0 to 7.8 +/- 1.0%, a reduction of 1.1% (P < 0.001) and changed the mean FPG level from 193.4 +/- 46.2 to 152.6 +/- 37.0 mg/dL, a reduction of 40.8 mg/dL (P < 0.001). Finally, the DPP4i add-on reduced HbA1c levels by 1.3% (from 9.1 +/- 1.3 to 7.8 +/- 1.4%,P < 0.001) and FPG levels by 39.3 mg/dL (from 190.7 +/- 45.3 to 151.4 +/- 41.6 mg/dL,P < 0.001). Patients with higher baseline HbA1c levels (>= 9.0%) showed a better response to quadruple therapy than those with baseline HbA1c levels lower than 9.0% for all three regimens. Conclusion Quadruple oral hypoglycemic therapy can be a feasible option in patients with T2D.