The patients’ background characteristics are presented in Table 1. A total of 884 patients were analysed. The mean patient age was 47.0 ± 8.1 years, and 90.2% patients were male. At the start of the observation period, the number of internal medications was 2.4 ± 1.8 and the rate of PP, defined ≥6 internal medications, was 6.7%. DPP-4 inhibitors were the most commonly used hypoglycaemic medications, followed by biguanides, α-glucosidase inhibitors and sulfonylureas. The number of medications and proportion of diabetes drugs are presented in Fig. 1. At the end of the observation period, the frequency of the use of diabetes drugs and combination therapy tended to increase compared with those at the start of the observation period. Multivariate analysis with PP as the objective variable (Table 2) revealed statistically significant difference for age 40â€"49 years (OR: 2.71, 95% CI: 1.02â€"7.22, p = 0.046), 50â€"59 years (OR : 2.96, 95% CI: 1.10â€"7.99, p = 0.032) and ≥60 years (OR: 4.43, 95% CI: 1.31â€"15.0, p = 0.017) compared with that for age <40 years; for total number of consultations during the 3-year observation period of 11â€"20 times (OR: 5.56, 95% CI: 1.56â€"20.0, p = 0.008), 21â€"30 times (OR: 9.63, 95% CI: 2.82â€"32.8, p < 0.001) and ≥30 times (OR: 11.6, 95% CI: 3.52â€"38.5, p < 0.001) compared with 1â€"10 times and for body mass index (BMI) ≥25 kg/m2 (OR: 1.71, 95% CI: 1.04â€"2.80, p < 0.033).
Table 1 Patients’ background characteristics. Figure 1Number of medications and proportion of diabetes drugs. The number of medications and diabetes drugs at the start (a) and end (b) of the observation period are shown. At the start of the observation period, many diabetes drugs were used, whereas at the end of the observation period, the use of combination therapy showed an increasing trend.
Table 2 Factors associated with polypharmacy at the end of the observation period, multiple logistic regression model.The median PDC was 79.6% (31.7â€"96.1), and 50.2% of the patients showed poor medication adherence. Receiver operating characteristic (ROC) analysis for the total number of consultations for PDC < 80% revealed that the cut-off value was 17 times during the 3 years (area under the curve: 0.86, sensitivity: 95.9%, specificity: 60.6%). Multivariate analysis with PDC < 80% as the objective variable (Table 3) revealed that statistical significance was observed for 2â€"3 medications (OR: 0.34, 95% CI: 0.22â€"0.51, p < 0.001), 4â€"5 medications (OR: 0.13, 95% CI: 0.08â€"0.23, p < 0.001) and ≥6 medications (OR: 0.18, 95% CI: 0.10â€"0.34, p < 0.001) compared with 1 medication at the end of the observation; male sex (OR: 2.20, 95% CI: 1.18â€"4.08, p = 0.013); total number of consultations <17 times (OR: 27.1, 95% CI: 15.6â€"47.0, p < 0.001) and age 50â€" <â€� �60 years (OR: 0.39, 95% CI: 0.23â€"0.68, p < 0.001) and ≥60 years (OR: 0.37, 95% CI: 0.15â€"0.89, p = 0.026) compared with <40 years.
Table 3 Factors influencing poor medication adherence, multiple logistic regression model.The present study revealed that the risk factors for PP were older age, high total number of consultations and BMI ≥ 25 kg/m2. The rate of PP occurrence in the present study was 6.7%, much lower than the approximately 50% rate previously reported12. The low rate may be attributed to our patients being younger (47.0 ± 8.1 years) and the presence of fewer comorbidities owing to the exclusion of patients with a history of prescription for hypoglycaemic medications. In the presence or absence of diabetes, the prevalence of hypertension and dyslipidaemia increases with age11,13. In addition, the risk of T2DM onset increases during the middle years of life14; therefore, the duration of diabetes becomes longer as age increases. Simultaneously, the incidence of microangiopathy and its related disorders also increases15,16, thereby causing an increase in the risk of PP. Patients with a high total number of consultations are likely to have poor medical condi tions and multiple complications. Thus, such patients may become polypharmic; however, further investigation is necessary to confirm this aspect. In overweight diabetic patients (BMI ≥ 25 kg/m2), the accumulation of visceral fat is a known risk factor for cardiovascular events17; these events adversely affect blood pressure, lipid metabolism and blood glucose control. Risk of PP increases as drug therapies according to guidelines are initiated for each disease.
Next, we investigated the factors associated with poor medication adherence and found that OR was the lowest in the cohort with 4â€"5 internal medications and that ORs with ≥6 medications were only slightly increased. Several studies reported that T2DM with a high number of medications18 and complications19,20,21,22 had a positive association with adherence. These reports could partially explain why participants with 4â€"5 medications in the present study had a lower barrier for medication. On the other hand, medication adherence assumedly decreases as the number of internal medications increases and usage becomes more complicated; therefore, we believe that OR for good medication adherence can be achieved with ≥6 medications, which is marginally higher compared with 4â€"5 medications.
In accordance with previous studies23,24,25, there was a distinct trend for increased adherence with increasing age in the present study. Male sex was a risk factor for poor medication adherence in the present study; nevertheless, the relationship between sex and medication adherence remains to be established. Males were reported to have a higher medication adherence than females23; however, several studies reported24,25,26 no sex-related differences in medication adherence. Analysis of the relationship between medication adherence and total number of consultations during the observation period resulted in a cut-off value of 17 times. Multivariate revealed found that <17 consultations during the observation period was a risk factor for poor medication adherence. Optimisation of prescriptions considering the patient’s condition and the decreased frequency of guidance to medication adherence by pharmacists may have led to a lower frequency of consultations. Furthermore, it i s possible that missed consultations or treatment interruptions are reflected in the lower frequency of consultation; therefore, this became a risk factor for poor medication adherence. Differences in medication adherence were expected depending on the class of the drugs because the methods of taking hypoglycaemic medications are diverse (e.g. once a day after meals or thrice a day immediately before every meal); however, there was no such differences were observed.
This study had several limitations. First, this was a retrospective study conducted using a large-scale receipt data; therefore, information and selection biases, may have affected the results. Second, owing to the small number of patients aged ≥ 65 years, it was difficult to examine whether this age range was a risk factor for PP. Third, as most patients were male, further analyses are required to determine whether these findings apply to females as well. Finally, in this study, whether the medication was administered to inpatients or outpatients could not be distinguished. Medication management during hospitalisation may be performed by a medical practitioner, which may affect the outcomes of PDC.
Risk of PP is high in elderly patients and in patients with a high BMI. To avoid PP in such patients, evaluation and implementation of an appropriate drug therapy are necessary. Furthermore, higher numbers of consultations over a certain period are associated with a higher risk of PP. The good medication adherence observed in this study suggests that the prescriptions were optimised such that good medication adherence was possible even with PP. It is necessary to consider just how well patient prescriptions are optimised in clinical practice to determine if there is room for further improvement via intervention. The efficacy of telemedicine, such as online medical treatment to avoid increasing patient burden from frequent visits, should also be examined. Finally, although PP was speculated to be a risk factor for poor medication adherence, the contrary was observed in this study.
