Aim : The purpose of this study was to evaluate the clinical efficacy of four oral hypoglycemic agents combination therapy (4-OHA) in patients with poorly controlled type 2 diabetes mellitus (T2DM) who cannot accept insulin therapy.
Methods : Forty-seven patients with T2DM were enrolled according to the following criteria: 1) HbA1c > 8.5% (69 mmol/mol); 2) ongoing treatment with 3-OHA combination (metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitor); 3) limitations for the application of insulin therapy. The patients were administered the fourth OHA (pioglitazone) in addition to the previous treatment for 24 months. We evaluated changes in HbA1c, body weight, hypoglycemia events, and side effects. The control group consisted of 50 patients who underwent basal insulin therapy under identical clinical conditions.
Results : At study completion, there were no significant differences in HbA1c improvement between the 4-OHA group and the control group [-1.41 vs -1.56% (-15.4 vs -17.1 mmol/mol), P=0.207]. There were also no differences in hypoglycemic events (n=10 vs 14, P=0.298) and weight gain (+2.79 vs +2.30kg, P=0.21)
Conclusion : The 4-OHA combination therapy has sufficient glucose lowering effects in some patients. When insulin is not feasible, 4-OHA combination therapy may be considered as an alternative therapy.

Therapeutic effect of 4 oral hypoglycemic agent in patients with type 2 diabetes mellitus who have limitation to insulin