Impact of Fixed Combination of Metformin and Pioglitazone on Insulin Resistance of Patients with Type 2 Diabetes: Results of a Randomized Open-Label Study

Rui Sun,* Lu Yuan,* Yun Shen,* Ziyang Shen, Bo Ding, Jianhua Ma Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Ding; Jianhua Ma, Email dingbonanjing@sina.com; majianhua196503@126.comAim: To compare the effect of metformin, a fixed combination of metformin and pioglitazone, or dapagliflozin on insulin resistance in patients with newly diagnosed type 2 diabetes.Methods: In this 6-week randomized open-label trial, 58 patients were randomly assigned to insulin with metformin, a fixed combination of metformin and pioglitazone, or dapagliflozin for 4 weeks. Hyperinsulinemic euglycemic clamp tests and FreeStyle Libre Pro Sensor were used to evaluate the insulin sensitivity represented by glucose-infusion rate (M value) and glycemic control, respectively. The main outcome was changes in insulin resistance compared with baseline.Results: The baseline characteristics were well matched among the three groups. When compared to baseline, insulin sensitivity after treatment was significantly improved. Further study revealed that the fixed combination of metformin and pioglitazone provided superior M-value improvement compared with metformin, but not different from dapagliflozin. Moreover, a greater reduction in insulin dose was observed in the fixed combination of metformin and pioglitazone group than the metformin or dapagliflozin group. However, there were no significant differences in the parameters of glycemic control within the groups.Conclusion: In patients with newly diagnosed type 2 diabetes, a fixed combination of metformin and pioglitazone provided greater improvement in insulin resistance than metformin alone and similar changes in insulin resistance to dapagliflozin.Keywords: insulin resistance, metformin, pioglitazone, dapagliflozin, type 2 diabetes