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This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day).Fifty patients were randomly allocated to the control group (maintaining the initial low-dose of metformin) and the dose increase group (up-titrating of metformin to 1,500-2,250 mg/day) for 24 weeks. The primary outcome was change in HbA1c from baseline to 24 weeks.Among the 25 patients allocated to the dose increase group, four patients were not able to complete the study protocol because of gastrointestinal symptoms. HbA1c in the dose increase group was significantly but modestly lower than in the control group (change in HbA1c: 0.22 ± 0.57 vs. -0.15 ± 0.58%, group comparison, P 0.05). The dose increase group did not gain weight during the study period, and no hypoglycemic events were reported in both groups. The rate of gastrointestinal symptoms in the dose increase group was profoundly higher than in the control group (32 vs. 0%, P 0.01).In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain.

A definition of Flexible Manufacturing System has not been necessarily clarifiedyet; An understanding, and an objective of its application are different in a variety of industries. In Toyota, on the basis of market-oriented production, FMS is understood as follows: o 1. The ultimate objective of applying FMS is to provide a manufacturing system which may flexibly respond to changes in a market. The flexible response means to supply timely a product as demanded by a customer. 2. Therefore, we should understand FMS as an extensive system from a product design through a product distribution, but not as a system limited to a process in manufacturing. In order to get all subsystems to work out as an organic whole, we believe that amanagement system should be prepared concurrently. A general idea of FMS (FMMS), which is conducted in Toyota, is illustrated fromsuch viewpoints as need, scope, objective, and measurement of evaluation. We also introduce various activities relating shortening the lead time in production, and in production planning and production ordering.