Introduction
Diabetes is one of the fastest increasing diseases in prevalence worldwide, and its prevalence was estimated to be 463 million individuals in 2019. Medical expenditure associated with diabetes accounted for $76 billion in 2019, approximately 10 % of the total [
1]. Various types of potent oral or injectable medications are now available for daily practice. However, a Japanese study revealed that more than half of all patients with diabetes do not achieve the target level of blood glucose, below 7.0 % (52 mmol/mol), [
2] which is recommended by the Japanese Diabetes Society [
3]. One of the potential causes of poor glycemic control may be insufficient adherence to medication. According to the studies about medication adherence in diabetes treatment, depression and medical costs are found to be consistent factors in systematic review [
4]. Also, age [
5], self-efficacy [
6], and personality traits [
5] are potential factors to be associated with medication adherence. However, knowing underlining potential factors does not mean to solve nonadherence problems because multiple factors may exist in each individual patient and some of them are not modifiable.
In addition to adherence, persistence with medication is another critical issue. Some studies using administrative claims databases of relatively large samples presented specific rates of persistence [
7,
8]. Comparative analysis across types of drugs were also reported [
9] and could be applied in selecting medications to lower the risk of discontinuation. Those analyses reflected real-world circumstances but did NOT give reasons for discontinuation of prescribed pharmacotherapies.
An integrated guidance document suggested methods to improve attendance at scheduled appointments for diabetes care [
10]. That document, based on various surveys and reports in the literature, cited reasons for dropouts from the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) [
11]. Its endpoint of discontinued appointments could be a valuable source for estimating medication persistence among the population with diabetes, although the consequences of discontinuation could not be tracked.
The primary purpose of this study was to investigate the specific characteristics of participants who discontinued pharmacotherapy for the treatment of diabetes in comparison with those who did not in right of the associated factors with glycemic control in each patient group. The secondary one was to quantify the reasons for discontinuation of diabetic pharmacotherapy.
Discussion
No obvious relationship was observed between medication adherence and glycemic control in the Discont group, although it was demonstrated that better adherence is relevant to better glycemic control in the Cont group. While a cross-sectional study like this one does not confirm causality, many other longitudinal studies found that medication adherence contributes to the control of blood glucose levels [
18‐
20]. Those who discontinued pharmacotherapy in the past would not be the same as those who discontinued in light of the impact of medication to the blood glucose. Participants with diabetes in the Discont group tended to be less medication adherent compared with those in the Cont group as seen in the difference of the MMAS-8 score distribution. It means that participants in the Discont group do not take medication as good as those who in the Cont group. Also, those who in the Discont group were not so convinced and accepted to take medication as those who in the Cont group, since ‘adherence’ is conceptually grounded on agreement with recommendation from medical professionals or care providers [
21]. As presented in the reasons for resumption of pharmacotherapy in the Discont group, recognizing subjective symptoms or being notified worsening HbA
1c, have influenced to change their behaviour. However, the degree of understanding in true seriousness of diabetes as the risk of causing micro- and macro-vascular complications may be different in the two groups.
The proportion of current smokers was similar between the Discont (18 %) and Cont (21 %) groups. However, the risk of uncontrolled HbA1c was 3.56-fold higher among smokers than non-smokers in the Discont group, while the risk did not increase significantly among smokers over non-smokers in the Cont group. Consumption (one pack per day in more than 90 % of the smokers), duration of discontinuation, and duration of smoking history were comparable between the two groups. The mean (± SD) smoking duration in the Discont and Cont groups was 31.5 (± 10.9) and 25.7 (± 10.8) years, respectively (data not shown).
Smoking is known to be associated with elevated HbA
1c level [
22], incidence of chronic kidney disease [
23] and incidence of stroke and cardiovascular disease [
24]. Thus, patients with diabetes are strongly advised by physicians-in-charge to quit smoking, as recommended in treatment guidelines [
3]. Among the current smokers in the Discont and Cont groups, proportion of the patients categorized as highly adherent in the MMAS-8 score were 23 and 33 %, respectively (data not shown). The assumption could be made that smokers in the Cont group do not follow their physicians’ advice on smoking cessation but adhere to medication protocols. On the other hand, smokers in the Discont group do not comply appropriately with medication protocols and possibly other forms of self-care management like diet or exercise and consequently are less likely to achieve the target HbA
1c level.
Familial history of diabetes was found to be different between the Dicont and the Cont groups in terms of relationship with the control of HbA
1c. In the Cont group, the risk of uncontrolled HbA
1c of those who have family member(s) with diabetes were 58 % lower than that of those who don’t. There may be positive effects of having family member(s) with diabetes: e.g. receiving instruction about disease and treatment, sharing ideal diet on a daily basis, having better support and care at home, and so on. Also, they might have faced unfavourable seriousness of diabetic complications and had fears, which they would like to avoid. These factors would encourage them to cope with medication and other self-care management properly. While, in the Discont group, there was no significant relationship between the familial history of diabetes and the level of HbA
1c control. Proportion of those who have family member(s) in the Discont group (51 %) was slightly higher than in the Cont (43 %) group. A study revealed that having close relatives with diabetes were more complicated in their explanatory model of disease than those who did not have [
25]. It suggested that what they learn from their relatives and their sense of efficacy or fear were interrelated in their making decision of treatment behaviour. The difference between the two groups found in the present study may attribute to individual factors that we did not investigate, e.g. family support in the management of diabetes, employment status, participation in educational programs for diabetic patients, etc.
More than 70 % participants in the Discont group decided to discontinue pharmacotherapy without consulting a medical professional. Moreover, almost half of those cases of discontinuation were associated with ‘disease perception,’ for example, ‘I was in good shape,’ ‘I thought that I did not need to go to hospital,’ and ’I thought that treatment was unnecessary,’ which implies inappropriate understanding of diabetes and its treatment. These responses were shown in some reports in the past [
10,
15‐
17], however in our knowledge no studies have been published on how large patients have inappropriate disease perception. It is the primary basis that patients with diabetes should lower their HbA
1c levels even if they do not experience subjective symptoms. This must have been instructed by physicians, pharmacists, or other medical professionals at diagnosis and when diabetic individuals begin receiving medication. Notwithstanding, why did they think this way?
According to Festinger’s cognitive dissonance theory [
26], we have an inner driver to hold all our attitudes, behaviour, and beliefs in harmony and avoid disharmony (dissonance). When there is an inconsistency among them, we want to change one or more of them to reduce or eliminate such inconsistency. A typical example is the smokers who want to quit smoking but cannot achieve it. They face an inconsistency between ‘belief that smoking is not good for health’ and ‘behaviour of continued smoking’. In this situation, changing the belief, e.g. ‘smoking may be harmful but
not for me,’ and ‘smoking is not so damaging because there are many smokers who live long and healthy,’ would be made because it is easier than changing the behaviour. Likewise, those who showed inappropriate disease perception in the Discont group in the above might be in the situation of inconsistency between ‘belief that taking medication every day is necessary for my disease’ and ‘behaviour that missing doses.’ Then, they would change the belief, e.g. ‘I do not need to take medication because I am fine.’
The inappropriate disease perception in the Discont group can be also explained by Kahneman’s theory in the field of behavioural economics [
27]. They do not act based on a rational balance of risks and rewards, which is assumed in classical economic theory, but often do make irrational decisions. To execute ideal self-care management of diabetes involves laborious efforts to change their daily routines and personal preferences as well as possibly fear of drug-related adverse reactions. Rewards for these burden and risks that incur in the near-term is limited and true benefits, namely preventing diabetic complications, are postponed to the distant future. In this intertemporal decision making across present and future, they are likely to have ‘cognitive bias’ [
28]. Depending on the degree of patience and self-control ability, they instinctively presume future value as small from the present standpoint and then struggle to change behaviour for the purpose of future benefits. As a result, it suppresses changing the behaviour in an objectively ideal direction. More importantly, they are not aware of the bias by themselves. If this is the case for patients, it is understandable for medical professionals to have difficulty to find better solution for effective intervention. According to Avorn [
29], ‘Despite a growing number of publications about the psychology of decision making, most medical care is still based on a “rational actor” understanding of how we make decisions.’ Although it is yet fully embedded in clinical practice, various interventional studies considering the cognitive bias have already made [
30‐
32] and further pragmatic research and real-world implementation are expected.
Among the triggers for resuming medication in the Discont, ‘receiving worsening of HbA1c level’ and ‘recognition of subjective symptoms’ accounted for 40 % and 30 %, respectively. Many who discontinued pharmacotherapy did not resume it until they were able to reach an understanding of their state of diabetes. Meanwhile, their disease might have advanced in the absence of pharmacotherapy. In this study, the complication rate in the Discont and Cont groups were 15 % and 10 %, respectively, which was not significant. Further investigations in larger populations are needed to analyse in depth underlying reasons for both discontinuing and resuming treatment among individuals with diabetes.
The first study limitation that should be cited is the potential for recall bias concerning reasons for discontinuing and resuming pharmacotherapy because this was a retrospective study design. It is generally difficult to access those who withdraw from treatment in a prospective study because they disappear from the cohort and only a few can be tracked individually thereafter. The present study design allowed the collection of sufficient data to analyse such patients quantitatively. Second, the patients registered in the research company consisted of 59.6 % in male and 16.0 % in the elderly. Its gender balance was almost comparable to the proportion of the elderly and less than that of the entire Japanese diabetic population. This is primarily because of the nature of an internet-based survey. However, because the purpose was to clarify the critical issue of poor adherence with medication regimens, which is likely to occur more in the non-elderly [
6], a survey sample of this study was considered medically valuable.
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