Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations

Abstract

Background: Insulin therapy is the treatment of choice in type 2 diabetes mellitus (T2DM) patients who are not achieving glycemic goals despite triple oral hypoglycemic agent (OHA) combination therapy. However, there is still no additional treatment option for patients who cannot afford insulin therapy or who have various clinical limitations. The purpose of this study was to evaluate the clinical efficacy and safety of four OHA combination therapy in poorly controlled T2DM patients who could not afford insulin therapy. Methods: Forty-seven T2DM patients were enrolled according to the following criteria: 1) glycosylated hemoglobin [HbA1c] > 8.5%, 2) ongoing treatment with 3 OHA combination therapy (metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitor), or 3) combined limitations for applying insulin therapy. Patients were given the fourth OHA (pioglitazone) in addition to their previous treatment for 12 months. We evaluated changes in HbA1c, body weight, hypoglycemic events, and side effects. Results: At study completion, mean HbA1c and fasting plasma glucose were significantly reduced from 9.6% to 8.04% and from 198.4 mg/dL to 161.5 mg/dL, respectively (P < 0.001). Mean body weight was significantly increased from 66.7 kg to 69.3 kg. Hypoglycemia and side effects were observed 18 times and only 3 cases showed abnormal liver function tests or edema. In addition, subjects with higher initial HbA1c levels and HOMA-beta showed an independent association with a greater reduction in HbA1c. Conclusion: The 4 OHA combination therapy is effective and safe when insulin is not feasible.