Article Type : Short commentary
Authors : Bando H
Keywords : Ministry of Health, Labor and Welfare (MHLW); National Health Insurance (NHI) drug price; Oral hypoglycemic agent (OHA); Evildagliptin and metformin (EquMet); National medical expenses
Some oral hypoglycemic agents (OHAs) exist for type 2 diabetes (T2D), such as metformin (Metgluco) and imeglimin (Twymeeg). For combined OHA, vildagliptin-metformin hydrochloride (EquMet) has been known for clinical effect. The Ministry of Health, Labor and Welfare (MHLW), Japan decides National Health Insurance (NHI) drug price for years. According to NHI pricing in April 2024, Metgluco as 250mg and 500mg became the same price of 10.1 Japanese Yen (JY). EquMet HD (high dose)/LD (low dose) is lower than Equa as 50.2, 51.0, and 60.6 JY, respectively. This trend comes from the MHLW policy for intending decreasing national medical expenses.
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.
Table 1: Several representative OHAs in topics with pharmacological price in 2024.
Type |
Oral Hypoglycemic Agent |
yen / 1Tab |
yen / day |
remarks |
Biguanide |
||||
Metformin (Metgluco) 250mg |
10.10 |
40.4 |
4 Tab for monotherapy |
|
Metformin (Metgluco) 500mg |
10.10 |
20.2 |
2 Tab for monotherapy |
|
DPP4-i |
||||
Vildagliptin (Equa) 25mg |
60.60 |
121.2 |
2 Tab for monotherapy |
|
EquMet LD |
51.00 |
112.0 |
Equa + Met 2 Tab /day |
|
EquMet HD |
50.20 |
100.4 |
Equa + Met 4 Tab /day |
|
Triazine ring |
||||
Imeglimin (Twymeeg) |
34.10 |
136.4 |
4 Tab for monotherapy |
|
SGLT2-i |
||||
Ipragliflozin L-Proline (Suglat) 25mg |
113.90 |
113.9 |
once in the morning |
|
Canagliflozin (Canaglu) 100mg |
158.50 |
158.5 |
” |
|
empagliflozin (Jardiance) 10mg |
188.90 |
188.9 |
” |
|
empagliflozin (Jardiance) 25mg |
322.60 |
322.6 |
” |
|
GLP-1RA |
||||
Oral semaglutide (Rybelsus) 3mg |
139.60 |
139.6 |
fasting in the morning |
|
Oral semaglutide (Rybelsus) 7mg |
325.70 |
325.7 |
” |
|
Oral semaglutide (Rybelsus) 14mg |
488.50 |
488.5 |
” |