The Specific Health Examination and Specific Health Guidance System, which were introduced in Japan in 2008, were designed to screen and identify patients with undiagnosed T2DM or metabolic syndrome. It was expected that through early detection and physician visit, the clinical course of T2DM or metabolic syndrome may have a better outcome. No reports have examined the effectiveness of the program. This analysis provides important insight into the association of the timing of physician visit, early intervention, and progression of the treatment course of T2DM in the Japanese population, through analysis of claims data from the largest claims database, JMDC, which includes data from approximately 5.2 million people.
The key significance of this study is the demonstration of the benefit of early consultation after the detection of hyperglycemia at a health checkup in the claims-based cohort setting. In this study, early physician visit was associated with a delay in requiring prescription of first-line (92 vs. 15 days, p < 0.0001) as well as second-line T2DM therapies (1599 vs. 1315 days, p < 0.0001). Among patients with baseline HbA1c from 6.5% to 8%, a higher percentage of patients in the early physician visit group were not prescribed antidiabetic drugs, in less than 2 months, compared to the delayed physician visit group. It is presumed that the patients were commenced on medical nutrition and exercise therapy for less than 2 months, which is recommended by the Japanese Clinical Practice Guideline for Diabetes. One possible explanation for the longer time to requiring first- or second-line T2DM medications is the early effect of glycemic control, known as “legacy effect” . On the basis of Supplementary Tables S3 and S4, the number of days between the first-line treatment and the second-line treatment was particularly large in the early physician visit group, indicating the potential effect of early physician visit and instituting diet and exercise therapy.
It is noteworthy that patients with comorbidities such as hypertension, dyslipidemia, and older age had an earlier first consultation with a physician. This may be due to prioritization of these patients by physicians after an abnormal HbA1c finding and increased cardiovascular risk profile. Equally, patients with comorbid conditions may seek earlier medical intervention because of health concerns. The higher prevalence rates of hypertension and dyslipidemia in the group who visited the hospital earlier may also be due to the earlier finding of hyperglycemia during patient visits for the treatment of comorbidities. The presence of hypertension and dyslipidemia has been reported to increase the risk of T2DM [18, 19]. However, despite the high prevalence of hypertension and dyslipidemia, subsequent antidiabetic treatment after an early visit (for the treatment of diabetes) was delayed. Since it has also been reported that antihypertensive drugs and antihyperlipidemic drugs affect the onset of T2DM [20, 21], it may be necessary to investigate the effect of early consultation on subsequent antidiabetic drugs and the progression of diabetic conditions in the population without hypertension or dyslipidemia. Usual care for hypertension and dyslipidemia may also affect the timing of diabetes treatment; these effects may also need further investigation.
The slower progression of the treatment course of T2DM associated with early physician visits in this study may result in significant economic benefits, with a potential reduction in costs from reduced diabetic complications and cost of T2DM medications . This potential economic benefit may be particularly important in the setting of an aging population with potentially increased T2DM prevalence in Japan . Therefore, not only early visit but also prevention of clinical inertia and appropriate diabetes education may lead to economic benefits, so it is necessary to pay attention to them, but further analysis is required in the future.
The Japanese guidelines recommend at least 2–3 months of treatment by lifestyle modifications before prescribing antidiabetic medications . However, in this study, 54.8% of patients were prescribed oral hypoglycemics in less than 2 months. In addition, combination therapy as first-line therapy was also more frequently observed in the delayed physician visit group. These deviations demonstrated a substantial gap between the national guidelines and the current clinical practice in Japan. If this is due to a lack of knowledge of the guidelines among physicians who diagnose and treat patients with T2DM, there may be a role for more intensive education on the benefits of lifestyle modification, to bridge knowledge gaps. Alternatively, this gap could be due to patients not adhering to physician advice , in which case, tailored educational efforts could be directed at patients. We believe further research may be required to better understand the practice gap in order to develop interventions enhancing T2DM patient care.
It is interesting to note that DPP4i was the most frequently prescribed T2DM therapeutic class in first-line therapy. In global T2DM guidelines, such as those of the American Diabetes Association , metformin is recommended as first-line pharmacological therapy. Metformin is a relatively safe oral hypoglycemic agent, with a well-established safety profile and is generally inexpensive. However, Japanese T2DM guidelines do not specify the order of use of different classes of T2DM therapies. Rather, physicians are encouraged to tailor therapeutic choice on the basis of patient characteristics, which partly explains the variance with international practice. The finding of DPP4i being the most frequently prescribed T2DM therapy in Japan is also consistent with previously published data from Nishimura et al. . Another possible explanation is that JMDC captured patients whose T2DM therapies were covered by insurance, therefore de-incentivizing prescribing physicians from limiting treatment costs.
The key strength of this study is the large pool of patients provided by the JMDC database, covering 5.2 million patients. As this is not a randomized controlled trial, many of the potential selection biases and confounding factors have been accounted for by using an adjusted model.
One limitation of this study is that the study design is not a prospective randomized controlled trial. In the study, the onset of T2DM was assumed to be at the time of an abnormal HbA1c reading at an annual health check. This is because in the JMDC database test values at the time of health check can be identified, but test values at the time of medical examination cannot be identified because of insufficient registration. But in reality, the commencement of the disease is insidious and likely to precede the time of abnormal HbA1c, and the actual time of onset of T2DM in each case is not known. Furthermore, the data captured for each patient are dependent on the quality of the information input by the healthcare professional, which is a common limitation in studies using electronic medical records. Another limitation is the demographic range of the patients in this database (20–74 years old), which does not cover a significant number of aged adult patients (75 years or older) with new-onset of T2DM [13, 27]. There was also a scarcity of data for patients aged 65 years or older in the dataset used in this study. Patient factors may also be a limitation, in that it was assumed that all patients filled their prescriptions and were adherent to their medication. In addition, this health check system is unique to Japan and may not be generally applicable to overseas subjects. Finally, as this study is a retrospective analysis from a claims database, some important data was not captured, which could have provided relevant information, such as reasons for stopping treatment, pill dumping or stockpiling, whether adequate diet and exercise treatment was instituted by the physician at the first visit and practiced by the patient, follow-up HbA1c at V2 and V3 time points, and the incidence of macro- and microvascular complications.