Combination therapy of alpha-glucosidase inhibitor, thiazolidinedione and sodium glucose co-transporter-2 inhibitor in japanese type 2 diabetes patients

Abstract

Background: We additionally administered selective inhibitor of sodium glucose co-transporter-2 (SGLT2) inhibitor to type 2 diabetic patients on α-glucosidase inhibitor (α-GI) and/or thiazolidinedione (TZD), to determine whether the multi-drug combination therapy including SGLT2 inhibitor further improved the glycemic control in Japanese patients with diabetes mellitus. Methods: The subjects were divided into four groups. Group I was administered an SGLT2 inhibitor in addition to ongoing treatment using hypoglycemic agents other than α-GI and SGLT2 inhibitor. Group II was administered an SGLT2 inhibitor in addition to an α-GI. Group III was administered an SGLT2 inhibitor in addition to a TZD. Group IV was administered an SGLT2 inhibitor in addition to an α-GI and TZD. The body weight and biochemical parameters were measured before and 1, 2 and 3 years after the start of SGLT2 inhibitor treat-ment. Results: In patients receiving α-GI or TZD, additional administration of an SGLT2 inhibitor resulted in a reduction of the body weight, body mass index (BMI) and serum uric acid level, but had little effect on the glucose or lipid metabolism. On the other hand, additional administration of SGLT2 inhibitor in patients receiving both α-GI and TZD (three-drug combination therapy) resulted not only in a reduction of the body weight, BMI and serum uric acid, but also in improvement of the glucose and lipid metabolism, with a reduction of the hemoglobin A1c level and increase of the serum high-density lipoprotein cholesterol level. Conclusion: The results suggest that three-drug combination therapy with α-GI, TZD and SGLT2 inhibitor, each of which has different mechanism of action, is beneficial for the treatment of type 2 diabetes mellitus.