Recently, novel oral hypoglycemic agent (OHA) includes imeglimin (Twymeeg) that has similar construction with Metformin. Other agents would be combination of vildagliptin and metformin (EquMet). Both Twymeeg and EquMet are provided twice daily (bid), where blood glucose variability can be improved for 24 hours. Japanese government and Ministry of Health, Labor and Welfare (MHLW) decides National Health Insurance (NHI) drug price for long, which is influenced by the interrelationships among MHLW, pharmaceutical companies, wholesalers, pharmacies and patients. According to NHI pricing in April 2023, EquMet is lower than Equa, which seems to be at least beneficial for diatetic patients
Abstract
Introduction
In recent years, several novel oral
hypoglycemic agents (OHAs) have been introduced to clinical practice. Among
them, imeglimin (Twymeeg) that has similar molecular construction has been in
topic [1,2]. On the other hand, the trend of combining existing OHAs has been
gradually observed. In particular, metformin has been attracted attention,
which was widely used as the first-line agent for Type 2 Diabetes (T2D) in the
world. One of the combined agents would be EquMet, which is vildagliptin (Equa)
and Metformin. It is the combination of DPP4-i and biguanide [3,4]. Some
perspectives are described in this article.
For decades, combined OHAs presented the matter of medical costs paid by the patients. From the economic point of view, long-term policies have been found by the Ministry of Health, Labor and Welfare (MHLW) [5]. In Japan, interrelationships among several organizations are important. They are i) Japanese government - MHLW - local government in each prefecture, ii) research and sales departments of pharmaceutical companies, iii) wholesalers that distribute a variety of medical agents, iv) pharmacies often located in front of the hospital, and v) each patient. These five organizations have mutual deep relationship. Various activities are carried out based on strict regulations such as the Pharmaceutical Affairs Law [6]. However, economic competition has been continued for actual practice. MHLW determines annual prices of medical agents which are based on the research and understanding of the development and distribution of medicine.
Table 1: Several representative OHAs in topics with pharmacological price.
Latest topic for OHA will be shown.
The author and collaborators major in diabetes and endocrinology associated
with various reports for years [7]. As to these areas, imeglimin (Twymeeg) has
attracted attention [8]. It has dual function for increasing insulin secretion
and decreasing insulin resistance [9,10]. The characteristic point includes the
administration of this agent for twice a day (bis in die, bid). Its suppression
of blood glucose levels at night is observed more than OHA once a day (quaque
die, qd) [11]. Similarly, vildagliptin (Equa) also shows benefit for better
clinical efficacy by bid [12]. It was confirmed by using 24-hour blood glucose fluctuations.
Then, EquMet is likely to give better glucose variability, which includes
vildagliptin and metformin twice a day.
Pharmacological pricing of several
representative agents will be described. In certain OHA combination drugs, the
drug price usually increases as the included components increase. On the other
hand, a case can be found where drug price is lower than monotherapy. This
interesting example would be EquMet combination Tablets LD or HD, including
vildagliptin and metformin [13]. The required drug price per tablet and per day
is summarized in Table 1. Among these, Equa has the advantage of significantly
lowering nocturnal blood glucose levels [12]. For impressive phenomenon, Equa
alone costs 65.3 yen, followed by Equa+Metformin 250 mg = 55.70 yen and
Equa+Metformin 500 mg = 55.0 yen. Then, daily required expenses will be doubled
up to 130.6 yen, 111.4 yen, and 111.0 yen, respectively. Considering the
exchange rate between USA and Japan, 1 dollar is equivalent to 135 Japanese
yen. In social medical insurance, many Japanese people are covered about 70-90%
of medical expense from government or social insurance services.
Several factors may be involved in
this phenomenon. MHLW in Japan has expressed continuous concern for rapid rise
in total annual medical expenditures for years [14]. As one of the
countermeasures, MHLW has adopted a policy suppressing medical costs by
increasing the use of generic agents rather than original agents. Among them,
two types of OHA have been tried to produce combined tablet, which costs less
than the total price. Annual pricing by MHLW was decided for April 2023, where
the price of Metformin-Equa-EquMet was changed (Table 1) [15]. These changes of
National Health Insurance (NHI) drug price were influenced by the interrelationships
of the five organizations mentioned above. Therefore, it requires to check the
evaluation after observing future progress. At the moment, this policy seems to
be beneficial, at least in part, for patients for diabetes.
In summary, latest topics about OHA
were introduced. What kind of direction does this matter develop in progress?
Several types of combined OHA have been introduced into clinical practice. This
may be similar to the trend towards combination of several inhalers into one for
bronchial asthma. After producing some combined OHAs, their pricing will be
changed. We would pay attention to pharmacological changes in the future.
Conflict of Interest
The authors declare no conflict of
interest.
Funding
There was no funding received for
this paper.