For the treatment of type 2 diabetes (T2D), metformin has been the first-line pharmacological agent from most previous research algorithms [1]. Its characteristic points include efficacy, safety and also affordability. In addition, clinical application of monotherapy and/or concomitant usage with other OHAs would be beneficial [2]. However, recent novel OHAs have changed the situation, including glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Both agents indicate renoprotective and cardioprotective benefits with various evidence [3]. In comparison with metformin, SGLT-2i showed lower rate of heart failure (OR 1.51), myocardial infarct (OR 1.45) and similar event ratio for stroke (OR 1.03) [3]. Then, first-line treatment of metformin for youth-onset T2D will be suboptimal in more than half patients within 2 years [4]. From clinical evidence point of view, it may be applicable for changes of first-line agent for T2D as mentioned above. However, when considering the actual clinical practice with various factors of cost-effectiveness and drug-naïve populations of T2D, actual significance of metformin for convenient management of T2D patients with low CV risk can remain solid in our usual medical practice [5].

Ministry of Health, Labor and Welfare (MHLW), Japan has continued medical management for long in Japan. Cost accounting system has conducted according to adding up material cost, manufacturing expenses, and so on [6]. The principle for deciding each cost for medical agent consisted from several factors. They include i) manufacturing (importing) cost such as material cost, personnel expenses, and manufacturing expenses, ii) sales cost with research cost, etc. iii) operating profit, iv) distribution cost, and v) consumption tax. Among these process, operating profit may vary drastically in the broad range of -50% to +100%. It depends on the degree of the novelty, efficacy or safety in comparison with the existing treatment so far. The determination method for drug price for the follow-on biologics. There are principles for two cases as follows: a) case of follow-on products by biotechnology. The drug price will become 0.7 multiplication of that of the original product. b) case of chemically synthesized products. The drug price will be calculated as 0.5 multiplication of that of the original product. Concerning a) and b), when the medicine is > 10 items 0.6 (for a) or 0.4 (for b) will be multiplied for the calculation [6].

Furthermore, recent topics about drug pricing of OHA in Japan will be introduced. The first is the pricing of Metformin. Two kinds of tablets for 250mg and 500mg had different prices until March 2024. New fiscal year starts in April 2024 in Japan. Both tablets were decided to have the same cost, which is 10.1 Japanese yen for one tablet of 250mg or 500mg [7]. Its price was set at the minimum level among all medical agents in Japan (Table 1). Metformin has been prescribed very frequently across the world. When it is provided 500mg, 1500mg, or 2250mg/day, the drug price cost would be 10.1, 30.3, 50.5 Japanese Yen (JY) per Tablet. The exchange rate would be 1 USD= about 150 JY.