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A Systematic Review of Interventions Addressing Adherence to Anti-Diabetic Medications in Patients with Type 2 Diabetes—Components of Interventions

Abstract

Background

Poor adherence to anti-diabetic medications contributes to suboptimal glycaemic control in patients with type 2 diabetes (T2D). A range of interventions have been developed to promote anti-diabetic medication adherence. However, there has been very little focus on the characteristics of these interventions and how effectively they address factors that predict non-adherence. In this systematic review we assessed the characteristics of interventions that aimed to promote adherence to anti-diabetic medications.

Method

Using appropriate search terms in Medline, Embase, CINAHL, International Pharmaceutical Abstracts (IPA), PUBmed, and PsychINFO (years 2000–2013), we identified 52 studies which met the inclusion criteria.

Results

Forty-nine studies consisted of patient-level interventions, two provider-level interventions, and one consisted of both. Interventions were classified as educational (n = 7), behavioural (n = 3), affective, economic (n = 3) or multifaceted (a combination of the above; n = 40). One study consisted of two interventions. The review found that multifaceted interventions, addressing several non-adherence factors, were comparatively more effective in improving medication adherence and glycaemic target in patients with T2D than single strategies. However, interventions with similar components and those addressing similar non-adherence factors demonstrated mixed results, making it difficult to conclude on effective intervention strategies to promote adherence. Educational strategies have remained the most popular intervention strategy, followed by behavioural, with affective components becoming more common in recent years. Most of the interventions addressed patient-related (n = 35), condition-related (n = 31), and therapy-related (n = 20) factors as defined by the World Health Organization, while fewer addressed health care system (n = 5) and socio-economic-related factors (n = 13).

Conclusion

There is a noticeable shift in the literature from using single to multifaceted intervention strategies addressing a range of factors impacting adherence to medications. However, research limitations, such as limited use of standardized methods and tools to measure adherence, lack of individually tailored adherence promoting strategies and variability in the interventions developed, reduce the ability to generalize the findings of the studies reviewed. Furthermore, this review highlights the need to develop multifaceted interventions which can be tailored to the individual patient’s needs over the duration of their diabetes management.

Introduction

Diabetes, characterized by hyperglycaemia, is one of the major chronic conditions that impacts a significant proportion of the population worldwide [1]. Diabetes is projected to be the 7th leading cause of death in 2030 [2]; with type 2 diabetes (T2D) accounting for most of the cases [2].

Management of T2D involves weight loss, via reductions in caloric intake and increases in physical activity, oral anti-diabetic agents and/or insulin [3, 4]. Non-pharmacological measures remain one of the key management recommendations, and are usually the starting point for patients diagnosed with T2D [3, 4]. Different classes of anti-diabetic agents are available for treatment, and dual, followed by combination therapy is recommended if mono-therapy is insufficient. Patients may ultimately require insulin replacement therapy to adequately manage their diabetes [4].

While adequate management of diabetes is extremely important for the prevention or delay of complications arising from poorly controlled blood sugar levels, the ‘chronic’ nature of the disease, lifelong requirement for medications, requirement for changes in lifestyle, the need to cope with social, cultural and psychological distress that may occur with the disease, and the clinical manifestations and associated complications, make the management of diabetes very complex. There is also a need to individually tailor the therapy for diabetic patients depending upon their age, demographic variability, co-morbidities and risk of developing complications [3].

Amidst this complexity, remaining adherent to treatment recommendations, such as home glucose monitoring, adjustment of food intake, administration of medication(s), regular physical exercise, foot care and regular medical visits [5] may be a challenge [6]. Adherence to medications has been recognized as key for optimally controlled diabetes [7, 8] in T2D patients.

Many factors affect adherence to treatment in diabetes such as disease and treatment characteristics and complexity, age, gender, self-esteem, stress, depression, quality of the relationship between patients and health care providers, social support, and patients’ ability to remain adherent amidst changing circumstances in their daily life [5]. The World Health Organization (WHO) has recognized five factors which influence adherence to all medications. They are health system related factors, socio-economic factors, condition related factors, therapy related factors and patient related factors [5]. Adherence is therefore a multifactorial behaviour and solutions require acknowledgment of the range of factors.

Studies have shown that medication adherence rates among patients with T2D is not optimal and is comparable to those with other chronic diseases [9]. Adherence to oral diabetes medications in T2D patients is 36 to 93% and to insulin is around 60% [10]. Treatment non-adherence in diabetes is well recognised, and interventions to promote adherence, improve glycaemic control, self-care behaviours and other key outcomes have been designed and implemented in T2D patients. Several reviews and meta-analyses published over the last decade have addressed these interventions in T2D patients [1123].

Some reviews have focused on the wider aspect of treatment adherence in diabetes, incorporating not just adherence to anti-diabetic medications but treatment adherence as a whole [14, 15, 20]. Where adherence to medications are specifically discussed [12, 17, 22, 23], the reviews have included studies that analysed adherence to a range of medications taken by T2D patients, rather than being specific to anti-diabetic medications [12]. Only a limited number of reviews have specifically evaluated interventions assessing adherence to anti-diabetic medications [17, 22, 23]. However, there has been very little focus on the characteristics of these interventions and how well they address factors that impact non-adherence.

Coincidentally, a review [24] examining interventions to improve medication adherence in patients with T2D was published at the same time as the current review was being finalized. However, the review has broad inclusion criteria and does not focus specifically on adherence to anti-diabetic medications. Furthermore, there was no in-depth categorization of the intervention components or an exploration of non-adherence factors addressed by the interventions. These are key gaps identified in the existing reviews of the literature. Therefore, the current review aims to assess the characteristics of the interventions, focusing on their components and evaluating how they address the factors that contribute to non-adherence to anti-diabetic medications. The specific objectives are to:

  • identify and categorise the intervention components which have led to improved medication adherence to anti-diabetic medications;
  • determine the WHO non-adherence factors that the interventions have addressed; and
  • evaluate changes in intervention designs and implementation techniques over time.

Methods

Literature search

A review of the literature was conducted to identify research articles that have evaluated the impact of interventions on adherence to anti-diabetic medications in T2D patients. Studies were searched in the following databases: Medline, Embase, CINAHL, International Pharmaceutical Abstracts (IPA), PUBmed, and PsychINFO. Each database was searched using the appropriate terms for medication adherence (concept 1), type 2 diabetes/ anti- diabetic medications (concept 2) and intervention studies (concept 3). Key words/ terms to denote these concepts were used and then combined using ‘and’ operator (concept 1 and concept 2 and concept 3) (S1 Fig). The search strategy was limited to articles published from January 2000 to April 2013 (inclusive) and published in English. The references of relevant publications (all studies included in this review and relevant systematic reviews [12, 14, 15, 17, 20, 21, 23] were hand searched to find additional studies that met the inclusion criteria (S1 Table). The search strategy as well as the study inclusion and exclusion criteria have also been illustrated previously [25].

Data extraction and analysis

For each study, the “intervention” and its characteristics were evaluated in-depth. The intervention components were summarised and the impact of each intervention was recorded. The interventionist(s), provision of training to the interventionist(s) before delivering the intervention, and the method of evaluating the delivery of the intervention were assessed. The interventions were categorised as recommended by Roter et al. [26]. Further information about the study characteristics can be found elsewhere [25].

Operational definitions

For the purposes of this review, the following operational definitions were used:

  • The term ‘medication adherence/ adherence’ has been used throughout the review to indicate the extent to which individuals take their medication, despite the alternative terms used in the studies included in the review.
  • Types of Interventions
  • Interventions have been classified into Educational, Behavioural and Affective, where appropriate, following the classification used by Roter et al [26]. Two additional categories were also used:
    • Educational: “pedagogic interventions, verbal or written, with a knowledge based emphasis designed to convey information. Specific strategies included one-to-one and group teaching, the use of written and audio visual materials, mailed materials, and telephone instructions” [26].
    • Behavioural: “interventions that were designed to change compliance by targeting, shaping, or reinforcing specific behavioural patterns. This included strategies such as skill building and practice activities, behavioural modelling and contracting, packaging and dosage modifications or tailoring, rewards, and both mail and telephone reminders” [26].
    • Affective: “strategies that attempted to influence adherence through appeals to feelings and emotions or social relationships and social supports. Included were family support, counselling, and supportive home visits” [26].
    • Economic: interventions that dealt with economic or cost related issues pertaining to medications.
    • Multifaceted: interventions that had components that could be categorized into more than one of the above categories.

Results

1. Study selection

The literature search identified 6,662 citations. A total of 230 articles appeared to meet the review inclusion criteria and were retrieved in full text. However, only 49 studies actually met the study criteria and were selected for review. Three more studies were identified from hand searching. Thus, a total of 52 studies [2778] were included [25] (S2 Fig).

2. Study characteristics

The majority (57.7%) of the studies were conducted in the USA and most (n = 38) were published in the last 5 years. Approximately half of the studies were ‘randomized controlled’ [28, 29, 31, 34, 35, 37, 39, 43, 4750, 56, 59, 60, 6264, 66, 67, 69, 72, 7577]. Participant inclusion criteria varied across the studies in terms of age, HbA1c value, duration since diagnosis, sample size and duration of study. Most of the interventions were carried in community settings (67.3%), and most were conducted for a maximum of 1 year, with the impact of a majority of the interventions being assessed for a duration of 6 months.

In addition to assessing anti-diabetic medication adherence as a primary (73.1%) [2733, 3538, 40, 4250, 5357, 59, 61, 64, 6872, 7477] or a secondary (26.9%) outcome, the studies assessed a range of other clinical or patient specific outcomes. The study characteristics have been discussed in detail previously [24].

The most widely used method for measuring anti-diabetic medication adherence was self-report, and the commonest tool reported was the Summary of Diabetes Self-care Activities (SDSCA) questionnaire. Overall, the methods for measuring anti-diabetic medication adherence varied across the studies, and the implications have been discussed elsewhere [25].

3. Interventions and their characteristics

3.1. Classifying the interventions.

Forty nine manuscripts dealt with interventions directed at the patient [2729, 31, 3351, 5378], two at the healthcare provider [30, 32], and one at both [52] (Table 1). Most (n = 40) [2730, 3243, 47, 48, 5056, 58, 6062, 6567, 69, 70, 7276, 78] were complex interventions with more than one component, and have been categorized as ‘multifaceted’. Others have been classified as educational (n = 7) [44, 45, 49, 59, 63, 68, 71], behavioural (n = 3) [31, 64, 77] or economic (n = 3) [46, 57, 68]. There were no interventions that were solely ‘affective’.

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Table 1. Intervention types, elements, WHO factors addressed and interventionists.

https://doi.org/10.1371/journal.pone.0128581.t001

The majority (n = 46) of the interventions had an ‘educational’ component [2730, 3245, 4756, 5863, 6572, 7476, 78]. Thirty eight had a ‘behavioural’ component [27, 2943, 47, 48, 50, 5256, 6062, 64, 67, 69, 70, 7278], and 23 interventions [28, 35, 37, 40, 41, 47, 48, 50, 5256, 58, 6062, 65, 66, 69, 72, 73, 75] had an ‘affective’ component.

3.2. WHO dimensions of non-adherence factors addressed by the interventions.

Most interventions addressed patient-related (n = 35) [2729, 31, 3335, 37, 38, 40, 41, 43, 45, 47, 48, 50, 5356, 58, 61, 62, 6473, 75, 77, 78], condition-related (n = 31) [2729, 3537, 3944, 4953, 55, 56, 5963, 66, 67, 69, 71, 74, 76, 78], and therapy-related (n = 20) [28, 29, 3337, 39, 44, 45, 4951, 53, 56, 60, 63, 67, 69, 70] factors. Only a few took into consideration the socio-economic (n = 13) [37, 40, 41, 46, 50, 52, 53, 57, 58, 65, 68, 69, 71] and health care system-related factors (n = 5) [28, 3032, 62]. While none covered all five, thirteen studies [28, 29, 35, 37, 40, 41, 50, 53, 56, 62, 67, 69, 71] addressed three or four factors. The remainder either addressed one (n = 18) [30, 32, 38, 42, 4648, 54, 57, 59, 64, 68, 7277] or two (n = 21) [27, 31, 33, 34, 36, 39, 4345, 49, 51, 52, 55, 58, 60, 61, 63, 65, 66, 70, 78] factors (Table 1). The details of the ‘telephonic diabetes education and support’ constituting one intervention were not provided, hence it was not possible to predict the factors that were addressed by the education program, although a general assumption could be made that multiple factors, patient related, condition related and therapy related factors, could have been included [68].

3.3. Interventionist(s).

Of those studies where the interventionist(s) was clearly identified, pharmacist(s) [28, 33, 34, 51, 60, 61, 63, 70, 75, 76] and nurse(s) [29, 36, 38, 42, 48, 53, 62, 66, 71, 72, 78] were involved in delivering the intervention in ten and eleven studies, respectively (Table 1). Community health workers (n = 2) [41, 52], peer supporters (n = 1) [65], bachelor level research assistants (n = 2) [31, 69], masters level research coordinators (n = 2) [50, 69], general practitioners/ clinicians/ physicians (n = 2) [30, 45] were involved in the other interventions. The educators involved, were either professional educators, for example diabetes educators (n = 3) [40, 44, 55], and health educators (n = 1) [67] or were behavioural coaches (n = 2) [47, 56]. Several authors reported the interventionist(s) simply as ‘investigator(s)’ [27, 39] or ‘researcher(s)’ [35]. A few studies did not specify who delivered the intervention [37, 49, 58, 64, 73], and in four studies, an interventionist was not applicable as the studies evaluated the impact of value based insurance designs or Medicare part D program [46, 57, 68]; or the intervention was a multimedia program [59].

3.4. Training to the interventionist and assessment of intervention delivery.

Interventionists were trained for intervention delivery in 36.5% of the studies (n = 19) [35, 38, 41, 45, 47, 48, 50, 52, 56, 58, 6062, 65, 67, 69, 70, 72, 75] and in only 11.5% of the studies was the delivery of the intervention assessed (n = 6) [45, 50, 58, 62, 65, 72] in order to determine how the intervention was delivered (Table 1).

3.5. Characteristics of interventions reporting improved medication adherence.

Approximately 41.5% (n = 22) of the studies [31, 32, 36, 44, 4954, 56, 57, 61, 63, 67, 69, 70, 72, 7477] reported improvements in medication adherence. The interventions reporting improved medication adherence were mostly multifaceted (n = 16) [32, 36, 5054, 56, 61, 67, 69, 70, 72, 7476], followed by educational (n = 3) [44, 49, 63], behavioural (n = 2) [31, 77], and economic (n = 1) [57]. In addition, the non-adherence factors addressed by the interventions had a similar trend. Five studies [50, 53, 56, 67, 69] addressed either three (n = 2) [56, 67] or four (n = 3) [50, 53, 69] factors, while nine [31, 36, 44, 49, 51, 52, 61, 63, 70] and eight [32, 54, 57, 72, 7477] studies addressed either two or one factor, respectively.

The interventionists involved in delivering these interventions varied. Pharmacists and nurses were involved in six [51, 61, 63, 70, 75, 76] and three [36, 53, 72] interventions, respectively. A nurse was also involved in another, along with a dietician and another professional [54]. Student level researchers were involved in three studies [31, 50, 69] and in two, they were referred to as ‘integrated care managers’ [50, 69]. Two studies mentioned respectively ‘health care professionals’ [44] and health care providers [74] were involved in leading the intervention sessions, without specifying who they were. “Coaches” [56] and Community Health Workers (CHWs) [52] were interventionists in other studies. Three studies did not specify who the interventionist was [49, 57, 77], and in two an interventionist was not required as these studies either evaluated the effect of implementing the Medicare part D program on anti-diabetic medication adherence [57], or the patients were delivered their OHAs in Real Time Medication Monitoring (RTMM) medication dispensers, which helped in registering their medication real time [77].

The interventionists were trained for the delivery of the study intervention in eight studies [50, 52, 61, 67, 69, 70, 72, 75]. Two studies [50, 72] assessed the delivery of the intervention process, while two others mentioned providing supervision of [67], and consultation with [75] the interventionists during the intervention delivery.

3.6. Characteristics of interventions reporting improvement in HbA1c.

HbA1c was an outcome measure in 64.1% of the studies (n = 34) [2729, 31, 3341, 43, 47, 5056, 5860, 62, 6467, 69, 71, 74, 78]; 16 of which [33, 36, 39, 5055, 58, 60, 64, 66, 67, 69, 71] reported a significant impact on HbA1c. More than 80% of these interventions were multifaceted, and more than 85% (n = 14) addressed two or more WHO non-adherence factors.

3.7. Characteristics of interventions reporting improvement in both medication adherence and HbA1c.

Out of the 34 studies that assessed the impact of interventions on both medication adherence and HbA1c, nine [36, 5054, 56, 67, 69] reported a positive impact on both medication adherence and HbA1c. However, in one study, the improvements in HbA1c were seen in patients with HbA1c>7%, rather than all participating patients [56]. The interventions were all multifaceted. In one study, the educational component was the primary component; however, it appeared that there was also a behavioural component, though it cannot be stated with certainty without obtaining more detailed information about the program [51]. Three studies [50, 53, 69] addressed condition-related, patient-related, therapy-related and socio-economic factors. Two others [56, 67] targeted the former three factors. One [54] was focused only on patient-related factors. Two addressed condition and therapy-related factors [36, 51], and one [52] addressed four: patient, condition, therapy and socio-economic-related factors. None addressed the health care system related factors.

Two studies [50, 69] included patients who had diabetes and depression and involved integrated care management for diabetes and depression. Both of these studies, published by the same authors, employed the same intervention strategy. The intervention was multifaceted, delivered by trained ‘integrated care managers’ and addressed patients’ individual, social and cultural needs, and was designed to improve medication adherence, glycaemic control and depression outcomes.

Two studies consisted of telephone-based interventions to improve diabetes control [53, 67]. One involved telephone calls conducted by nurses to deliver education about of diet, exercise and medication adherence [53]. In the other, participants received telephone calls from health educators primarily about diabetes medication adherence [67].

Other interventions consisted of SMS delivered by nurses to educate the patients and aid in reinforcement of diet, exercise and medication adjustment [36]; a diabetes education program delivered by community health care workers [52]; pharmaceutical care program [51]; integrated health coaching [56] and a cognitive behavioural therapy for adherence and depression [54].

3.8. Major elements in the intervention processes and changes over time.

Overall, interventions have been refined over time, both in terms of their design, and delivery. The majority of the interventions were multifaceted, with increasing incorporation of affective components, especially for interventions implemented since 2010. Approximately 35.7% of the interventions published prior to 2010 included an affective component compared to 42.1% after 2010.

Educating patients, individually or in groups, on various behavioural and medicine related issues has remained one of the most widely used strategies to promote adherence over the past 13 years. Similarly, using telephones has remained a popular strategy for delivering interventions and conducting follow-ups. However, more recently, mobile phones have been used to deliver educational messages as well as send text reminders as behavioural prompts (eg in collecting refills and taking medications) [36, 64, 78].

Interventions published, particularly after 2005, were more intensive and complex. The interventions not only addressed the patients’ knowledge gap and problems related to self-management practices, but also incorporated a range of other pertinent issues, for example ‘cognitive improvement’ [35], ‘cultural issues’ [37, 40], ‘inclusion of support person’ [37], ‘stress and stress management’ [37] and ‘self-efficacy’ [37, 47]. Concepts such as ‘integrated health coaching’ [56], ‘cognitive behavioural therapy’ [54, 62] were also implemented and evaluated. Goal setting as an intervention strategy was seen to emerge in the studies published after 2007 [43, 48, 56, 67]. Thus, over time the interventions have become more patient-centred attempting to address specific patient needs with focus on adding more affective approaches.

Use of technology for designing interventions was reported more in the studies published after 2005. Such, technology driven interventions, varied from simple strategies, for eg. using a cell phone or an internet to input blood glucose data and receive feedback [36], to the use of complex computer programs, such as NICHE technology [38] and Well Doc’s Proprietory Management Software System [39] for diabetes management.

Three studies, published since 2009 [46, 57, 68] have addressed the economic component, which had not been addressed previously.

Although interventions have become more complex in recent years, more ‘straightforward’ strategies such as delivering education materials, providing routine education sessions, and displaying multimedia programs in waiting room settings, are still used in some interventions. Moreover, the complex interventions have involved the addition of more patient oriented components to these ‘simple’ strategies, and these have proven slightly more successful than the ‘simpler’ ones.

Discussion

There has been a significant increase in the number of studies implementing and evaluating interventions aimed at promoting adherence to anti-diabetic medications, with the majority being conducted in the USA. Overall, the systematic review identified a range of intervention techniques which have been employed in an effort to improve self–care behaviours including adherence to anti-diabetic medications, in patients with T2D. The interventions were primarily directed at patients and ranged from simple educational interventions, including supply of educational materials, to complex interventions which took into consideration patients’ attitudes, practices and preferences in addition to educating and aiding them to adhere to therapy. In fact, a majority of the interventions were multifaceted, consisting of a combination of more than one educational, behavioural or affective strategy. The interventions were delivered mainly by nurses and pharmacists; only a few studies reported having trained the interventionist on delivering the intervention, and even fewer reported assessing the delivery of the intervention by the interventionists.

Only a few of the interventions reviewed reported a significantly positive impact on adherence to anti-diabetic medication, and even fewer had a positive impact on both medication adherence and HbA1c levels, a parameter assessed in most studies as the measure of glycaemic control. Most of these successful interventions were multifaceted, employing a combination of strategies. However, interventions with comparable approaches showed varying results, and made it very difficult to deduce the effective intervention components. It was outside the scope of this review to investigate the components and delivery of the interventions in-depth, to determine whether the interventions were developed appropriately and/or adequately delivered by the most suitable healthcare professional. This level of investigation requires access to process implementation data which may not have been collected by the original researchers.

Combination strategies have been recognized as more likely to enhance outcomes and reduce costs for patients with T2D [79]. Whereas this aspect is undoubtedly supported by the findings in the review, a few interventions which consisted of an educational, behavioural or economic component only, have also had an impact on anti-diabetic medication adherence. Overall, educational content was the most common component of the interventions. This indicates the importance of educating patients about their condition and its therapy as a first step in increasing awareness about the importance of adherence to treatment and motivating patients to take their medications to ensure improved disease management and better health outcomes. Moreover, educating patients through the provision of written materials, electronic media, and verbally, could perhaps be regarded as one of the simplest and most efficient strategies to implement when the goal is to promote patients’ adherence to their therapy. However, effective education and determining that patients have understood the information and that the information has not only increased knowledge but resulted in a behavioural change, presents a greater challenge to researchers, clinicians and healthcare providers involved in delivering interventions to patients with T2D.

Behavioural strategies, which are increasingly being used in adherence support interventions, range from adherence aids (eg dose administration aids) which address non-intentional adherence, to motivational interviewing and other more complex strategies, which aim to address several factors impacting patients’ medication taking behaviour. Non-adherence may be due to a multitude of factors, and a combination of educational and behavioural strategies provide a greater likelihood of addressing the factors that impede adherence in a broader group of patients. Additionally, diabetes management involves management of lifestyle issues, and therefore, it becomes quite important for patients to adapt to the changing circumstances. Behavioural component(s) would aid the patient in the process of adaptation, and educational strategies will provide the information needed to facilitate the behavioural changes. Thus, it is not surprising that most of the interventions designed over the last few years have consisted of both educational and behavioural components.

Affective components were employed from the earlier years although affective components have become more common in the later years, and are present in most of the interventions. Newer approaches such as inclusion of ‘peer supporters’ as interventionists, addressing cultural issues and ethnic beliefs, adding novel techniques like integrated health coaching, and addressing cognitive issues in the more recent years, has added to the ‘affective’ component, while also making the newer interventions more patient-centred. While simple individual counselling or an education session could be regarded as being focussed on a single patient, the impact would however depend upon the extent to which an individual’s psychosocial needs are taken into consideration. Psychosocial issues, such as attitudes about illness, affect, mood, diabetes related quality of life, resources, diabetes-related distress, and cognitive abilities have been recognised in recent years as important predictors of overall diabetes management [80]. Furthermore, from a global perspective, cultural issues and societal orientation have also been found to influence diabetes management [81, 82]. Issues such as these have been recognised as important predictors of adherence and diabetes management and been included in interventions, thereby increasing the ‘affective components’ in recent years.

Interactive technology is increasingly being explored for health promotion [83] and was also employed in adherence promoting interventions identified in this review, in order to deliver educational, behavioural and affective components, either singly or in combination. In its simplest approach, interactive technology was used to educate, remind, or provide advice to patients. Other examples of interactive technology used were the Well-doc System, NICHE technology, tele-health devices, and RTMM technology. These technologies enabled the collection and transfer of patient specific data/ information across to different professionals/ personnel, who could then deliver the tailored feedback and reminders to the patients. The increasing advancement in technology and benefits that can be received particularly with regard to patients being in contact with their care providers from home is an appealing prospect. Furthermore, technology driven interventions could have a greater reach, better adoption and implementation, and increased sustainability; thus having a greater positive heath impact [84]. However, more research is needed to establish the sustained effects of such technologies and to evaluate how such technologies can really be useful in the short and long term in promoting adherence to medications.

Human behaviour in itself is a complex phenomenon. It is therefore more likely that any intervention designed to influence human behaviour, such as modifying medication adherence or other self-care behaviours in patients with T2D, would be more successful if multiple factors that intertwine to aid the change in complex human behaviour are addressed. Combined interventions comprise of different components, which may act both independently and inter-dependently [85], to address the change(s) desired, and may be more effective than using a single component in isolation. However, complexity involved in designing, implementation, evaluating and replicating ‘combined intervention(s)’, often complicates the practicalities and interventions involving a single component may be preferred as they are easier to design, implement and replicate, and often times are successful in influencing a behaviour change.

It is recommended that the diabetes services be led by the needs of patients [80]. Hence, it is logical that interventions designed for a behaviour change are guided by patients’ need. Individualizing or tailoring strategies for behaviour change to the needs of the individual patients is more effective than a ‘generic form’ of any strategy; for example, tailoring health behaviour change messages have been found more effective than generic communications [86]. In tailoring an intervention, the strategies tend to be more patient centred. More than half of the interventions included in this review considered the individual patient’s circumstance(s) while delivering the intervention; however, the extent of individualization varied. Each component (educational, behavioural, affective or economic component) needs to be individualised, and rendered more patient centred. Williams et al have also emphasised the need for ‘tailored interventions’ to promote medication adherence in patients with T2D [24].

The factors affecting adherence to anti-diabetic medications have been inconsistently reported [87]. However, WHO has identified five factors that interact to influence patients' adherence behaviour [5]. WHO patient-related, condition-related, and therapy-related factors contributing to non-adherence were addressed by most of the interventions identified in this review. The socio-economic factors were addressed by fewer interventions and hardly any covered the health-care system related factors. However, there was a growing trend in the later years in incorporating socio-economic factors into the intervention designs. The impact of socio-economic factors and health care system related factors on medication adherence has been established particularly in cases of chronic diseases [81, 88], though their influences have been found to be 'inconsistent' [5]. As the evidence increases, it is likely that more interventions will include strategies to address socio-economic and health care system factors impacting adherence, as was seen in the more recent interventions identified in this review.

Financial or economic factors could become a major issue for patients with chronic diseases. Management of long term conditions such as diabetes and the consequences of poorly controlled diabetes could have an astounding economic impact on the patient and on each country globally [89, 90]. Although the magnitude of the impact is more likely to depend on the economic status of the patients, reduced out of pocket expenses have been identified as a factor that could improve medication adherence [91]. Only a few studies have looked into this aspect, with three identified as part of this review. One evaluated the impact of US ‘Medicare Part D’ program on adherence, another assessed the impact of generic substitution in reducing costs, and the third focused on the impact of a value based insurance program. Whereas the former was successful in improving medication adherence to anti-diabetic medications, the latter two were not. Nothing conclusive can be drawn about how cost impacts adherence from these studies. However, expenses in terms of medication taking, diabetes management, and the consequences of not adhering to medications could have a staggering economic impact [90]. More studies are therefore needed to explore the impact of a range of economic interventions. As mentioned, health-care system related factors, including healthcare professionals, were the least addressed WHO adherence factors in the interventions included in this review. Although health care providers like nurses, pharmacists and sometimes clinicians were involved in delivering the intervention, whether they had sufficient training in the matters relating to patient adherence behaviour was unknown. Their involvement could largely be observed as a supplier of patient-related, therapy-related and condition-related information and have been classified accordingly. Health care systems globally are intricate; effectively addressing health care system during trials could pose practical difficulties, which could be a reason for the small number of interventions addressing health care system related factors. However, as they cover quiet a significant expanse in patients' overall health care behaviour, it is necessary that these factors be explored and addressed effectively when designing future interventions for patients with T2D.

In summary, while most of the interventions addressed multiple factors, none were able to cover all five WHO factors. An ideal intervention would be one that explores and addresses all interacting factors through a tailored strategy to bring about a change in patient medication adherence [87]. However, nothing conclusive could be drawn from the studies included in this review, as to the successful intervention, as the majority were found to address only one or two of these interacting factors. The factors and the extent of their influence could vary between people, and is likely to be addressed by tailoring of the intervention. Further research also needs to focus on the 'extent' of the influence of the different factors. Ample consideration is needed in terms of how such interacting factors could be effectively addressed and incorporated to improve medication adherence.

Conclusion

Multifaceted interventions appear to be a more effective approach in improving medication adherence and glycaemic target in patients with T2D than individual interventions, as they provide a range of strategies to address a number of factors that may impact an individuals' adherence to their medications. Educational component formed the most widely used component in the interventions, followed by behavioural and affective components. While educational components have remained popular throughout, affective components have become more common in the later years. Nonetheless, it is extremely difficult to conclusively state which strategies are more effective, because interventions with similar components have proved to be successful in some studies and unsuccessful in others. Additionally the variation observed in research designs, and methods of outcome assessments, together with differences in patient characteristics prevented a detailed comparison of findings or a meta-analysis.

Patient-related, therapy-related and condition-related factors were addressed by most of the interventions. Health care system related factors were least addressed. While 'social' factors are increasingly being addressed, the focus on the 'economic' aspect is still lagging behind. In addition to effectively addressing all these factors, future research needs to focus on exploring the extent to which such factors influence an individuals' medication taking behaviour throughout the medication taking journey.

Overall, future research investigating development and evaluation of effective and sustainable adherence promoting interventions needs to include standardized methods and tools, and prioritize the needs and therefore tailor interventions to the needs of individuals.

Limitations of the Review

The diverse nature of the studies included in the review presents an important limitation preventing a detailed comparison of the interventions (and a meta-analysis). Moreover, studies included were not selected based on their quality. The review was conducted with a broad approach, and intended to include all studies addressing anti-diabetic medication adherence in patients with T2D irrespective of their quality. The components of the interventions and their categorization into the WHO factors for each study have been based only on the information provided in the manuscripts. This could have had an influence on those classifications where the interventions were not explained in sufficient detail. However, the authors have done their best to ensure proper identification of intervention components using the information provided.

Author Contributions

Conceived and designed the experiments: SS PA JEB. Performed the experiments: SS PA. Analyzed the data: SS PA. Wrote the paper: SS PA JEB JG.

References

  1. 1. Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2 7 million participants. The Lancet. 2011;378(9785):31–40. pmid:21705069
  2. 2. Alwan A. Global status report on noncommunicable diseases 2010: World Health Organization; 2011.
  3. 3. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care. 2012;35(6):1364–79. pmid:22517736
  4. 4. Kamar ME. Management of Type 2 Diabetes: From Guidelines to Personalized Medicine. Zagazig University Medical Journal 2012;18(5):826: 36.
  5. 5. Sabatâe E. Adherence to long-term therapies: evidence for action: World Health Organization; 2003.
  6. 6. Lerman I. Adherence to treatment: the key for avoiding long-term complications of diabetes. Archives of medical research. 2005;36(3):300–6. pmid:15925020
  7. 7. Bailey CJ, Kodack M. Patient adherence to medication requirements for therapy of type 2 diabetes. International Journal of Clinical Practice. 2011;65(3):314–22. pmid:21314869
  8. 8. Rhee MK, Slocum W, Ziemer DC, Culler SD, Cook CB, El-Kebbi IM, et al. Patient adherence improves glycemic control. Diabetes Educator.31(2):240–50. pmid:15797853.
  9. 9. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Comparison of Drug Adherence Rates Among Patients with Seven Different Medical Conditions. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2008;28(4):437–43.
  10. 10. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes care. 2004;27(5):1218–24. pmid:15111553
  11. 11. Blenkinsopp A, Hassey A. Effectiveness and acceptability of community pharmacy-based interventions in type 2 diabetes: A critical review of intervention design, pharmacist and patient perspectives. International Journal of Pharmacy Practice. 2005;13(4):231–40.
  12. 12. Doggrell SA. Does intervention by an allied health professional discussing adherence to medicines improve this adherence in Type 2 diabetes? Diabetic Medicine. 2010 Dec;27(12):1341–9. pmid:21059085.
  13. 13. Graziano JA, Gross CR. The effects of isolated telephone interventions on glycemic control in type 2 diabetes: A literature review. Advances in Nursing Science. 2009;32(3):E28–E41. pmid:19707085
  14. 14. Hearnshaw H, Lindenmeyer A, Vermeire E, Van Royen P, Wens J, Biot Y. Interventions to improve adherence to medication in people with type 2 diabetes mellitus: the role of nurses. European Diabetes Nursing. 2006;3(2):73–7. pmid:2009547320.
  15. 15. Lindenmeyer A, Hearnshaw H, Vermeire E, Van Royen P, Wens J, Biot Y. Interventions to improve adherence to medication in people with type 2 diabetes mellitus: A review of the literature on the role of pharmacists. Journal of Clinical Pharmacy and Therapeutics. 2006;31(5):409–19. pmid:16958818
  16. 16. Montori VM. Review: interventions focusing on patient behaviors in provider-patient interactions improve diabetes outcomes. ACP Journal Club. 2004;140(2):51–. pmid:2004096223.
  17. 17. Omran D, Guirguis LM, Simpson SH. Systematic review of pharmacist interventions to improve adherence to oral antidiabetic medications in people with type 2 diabetes. Canadian Journal of Diabetes. 2012;36(5):292–9.
  18. 18. Sigurdardottir AK, Jonsdottir H, Benediktsson R. Outcomes of educational interventions in type 2 diabetes: WEKA data-mining analysis. Patient Education and Counseling. 2007;67(1–2):21–31. pmid:17574367
  19. 19. van Dam HA, van der Horst FG, Knoops L, Ryckman RM, Crebolder HF, van den Borne BH. Social support in diabetes: a systematic review of controlled intervention studies. Patient education and counseling. 2005;59(1):1–12. pmid:16198213
  20. 20. Vermeire EI, Wens J, Van Royen P, Biot Y, Hearnshaw H, Lindenmeyer A. Interventions for improving adherence to treatment recommendations in people with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews. 2005 (2). pmid:2009824422.
  21. 21. Wens J, Vermeire E, Hearnshaw H, Lindenmeyer A, Biot Y, Van Royen P. Educational interventions aiming at improving adherence to treatment recommendations in type 2 diabetes. A sub-analysis of a systematic review of randomised controlled trials. Diabetes Research and Clinical Practice. 2008;79(3):377–88. pmid:17643546
  22. 22. Wilke T, Mueller S, Groth A. The methodological quality and effectiveness of adherence interventions: A review of diabetes type II interventions. Value in Health. 2010;13(7):A295–A6.
  23. 23. Zomahoun HTV, Guenette L, Moisan J. Interventions that improve adherence to oral antidiabetic in adults with type 2 diabetes: A systematic review. Journal of Population Therapeutics and Clinical Pharmacology. 2012;19(2):e135.
  24. 24. Williams JLS, Walker RJ, Smalls BL, Campbell JA, Egede LE. Effective interventions to improve medication adherence in Type 2 diabetes: a systematic review. Diabetes Management. 2014;4(1):29–48. pmid:25214893
  25. 25. Sapkota S, Brien J, Greenfield J, Aslani P. A systematic review of interventions addressing adherence to anti-diabetic medications in patients with type 2 diabetes-impact on adherence. PloS one. 2015;10(2):e0118296. pmid:25710465
  26. 26. Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Medical care. 1998;36(8):1138–61. pmid:9708588
  27. 27. Hendricks LE, Hendricks RT. The effect of diabetes self-management education with frequent follow-up on the health outcomes of African American men. The Diabetes educator. 2000;26(6):995–1002. pmid:11912812
  28. 28. Grant RW, Devita NG, Singer DE, Meigs JB. Improving adherence and reducing medication discrepancies in patients with diabetes. Annals of Pharmacotherapy. 2003;37(7–8):962–9.
  29. 29. Kim HS, Oh JA. Adherence to diabetes control recommendations: impact of nurse telephone calls. Journal of Advanced Nursing. 2003 Nov;44(3):256–61. pmid:14641395.
  30. 30. Maddigan SL, Majumdar SR, Guirguis LM, Lewanczuk RZ, Lee TK, Toth EL, et al. Improvements in patient-reported outcomes associated with an intervention to enhance quality of care for rural patients with type 2 diabetes: results of a controlled trial. Diabetes Care. 2004 Jun;27(6):1306–12. pmid:15161780.
  31. 31. Rosen MI, Rigsby MO, Salahi JT, Ryan CE, Cramer JA. Electronic monitoring and counseling to improve medication adherence. Behav Res Ther. 2004 Apr;42(4):409–22. pmid:14998735.
  32. 32. Schectman JM, Schorling JB, Nadkarni MM, Voss JD. Can Prescription Refill Feedback to Physicians Improve Patient Adherence? American Journal of the Medical Sciences. 2004;327(1):19–24. pmid:14722392
  33. 33. Wermeille J, Bennie M, Brown I, McKnight J. Pharmaceutical care model for patients with type 2 diabetes: integration of the community pharmacist into the diabetes team–a pilot study. Pharmacy World and Science. 2004;26(1):18–25. pmid:15018255
  34. 34. Odegard PS, Goo A, Hummel J, Williams KL, Gray SL. Caring for poorly controlled diabetes mellitus: A randomized pharmacist intervention. Annals of Pharmacotherapy. 2005;39(3):433–40. pmid:15701763
  35. 35. Keeratiyutawong P, Hanucharurnkul S, Melkus GDE, Panpakdee O, Vorapongsathorn T. Effectiveness of a self-management program for Thais with type 2 diabetes. Thai Journal of Nursing Research. 2006;10(2):85–97. pmid:2009193720.
  36. 36. Kim HS, Kim NC, Ahn SH. Impact of a nurse short message service intervention for patients with diabetes. Journal of nursing care quality. 2006;21(3):266–71. pmid:16816608
  37. 37. Vincent D, Pasvogel A, Barrera L. A feasibility study of a culturally tailored diabetes intervention for Mexican Americans. Biol Res Nurs. 2007;9(2):130–41. pmid:17909165
  38. 38. Faridi Z, Liberti L, Shuval K, Northrup V, Ali A, Katz DL. Evaluating the impact of mobile telephone technology on type 2 diabetic patients’ self‐management: the NICHE pilot study. Journal of evaluation in clinical practice. 2008;14(3):465–9. pmid:18373577
  39. 39. Quinn CC, Clough SS, Minor JM, Lender D, Okafor MC, Gruber-Baldini A. WellDoc mobile diabetes management randomized controlled trial: change in clinical and behavioral outcomes and patient and physician satisfaction. Diabetes technology & therapeutics. 2008;10(3):160–8.
  40. 40. Utz SW, Williams IC, Jones R, Hinton I, Alexander G, Yan G, et al. Culturally tailored intervention for rural African Americans with type 2 diabetes. The Diabetes Educator. 2008 Sep-Oct;34(5):854–65. pmid:2008-14587-009.
  41. 41. Babamoto KS, Sey KA, Camilleri AJ, Karlan VJ, Catalasan J, Morisky DE. Improving diabetes care and health measures among hispanics using community health workers: Results from a randomized controlled trial. Health Education and Behavior. 2009;36(1):113–26. pmid:19188371
  42. 42. Clarke A. Effects of routine education on people newly diagnosed with type 2 diabetes. European Diabetes Nursing. 2009;6(3):88–94. pmid:2010528855.
  43. 43. Glasgow RE, Edwards LL, Whitesides H, Carroll N, Sanders TJ, McCray BL. Reach and effectiveness of DVD and in-person diabetes self-management education. Chronic Illness. 2009 Dec;5(4):243–9. pmid:19933245.
  44. 44. Kolawole B, Adeola O, Adegbenro C, Akintan T, Adegoke S, Ojoawo I. Effectiveness of a structured diabetes education program on some non-glycemic endpoints in Nigerians with type 2 diabetes mellitus. International Quarterly of Community Health Education. 2009;29(4):381–8. pmid:19959429
  45. 45. Mullan RJ, Montori VM, Shah ND, Christianson TJ, Bryant SC, Guyatt GH, et al. The diabetes mellitus medication choice decision aid: a randomized trial. Archives of Internal Medicine. 2009 Sep 28;169(17):1560–8. pmid:19786674.
  46. 46. Rodin HA, Heaton AH, Wilson AR, Garrett NA, Piocher DW. Plan designs that encourage the use of generic drugs over brand-name drugs: An analysis of a free generic benefit. American Journal of Managed Care. 2009;15(12):881–8. pmid:20001169
  47. 47. Sacco WP, Malone JI, Morrison AD, Friedman A, Wells K. Effect of a brief, regular telephone intervention by paraprofessionals for type 2 diabetes. Journal of Behavioral Medicine. 2009 Aug;32(4):349–59. pmid:19365719.
  48. 48. Thoolen BJ, de Ridder D, Bensing J, Gorter K, Rutten G. Beyond good intentions: The role of proactive coping in achieving sustained behavioural change in the context of diabetes management. Psychology & Health. 2009 Mar;24(3):237–54. pmid:2009-03307-001.
  49. 49. Adepu R, Ari SM. Influence of structured patient education on therapeutic outcomes in diabetes and hypertensive patients. Asian Journal of Pharmaceutical and Clinical Research. 2010;3(3):174–8.
  50. 50. Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans: a randomized controlled pilot trial. Diabetes Educator. 2010 Mar-Apr;36(2):284–92. pmid:20040705.
  51. 51. Borges APDS, Guidoni CM, Ferreira LD, Freitas OD, Pereira LRL. The pharmaceutical care of patients with type 2 diabetes mellitus. Pharmacy World and Science. 2010;32(6):730–6. pmid:20734138
  52. 52. Castillo A, Giachello A, Bates R, Concha J, Ramirez V, Sanchez C, et al. Community-based diabetes education for latinos: The diabetes empowerment education program. Diabetes Educator. 2010;36(4):586–94. pmid:20538970
  53. 53. Cinar FI, Akbayrak N, Cinar M, Karadurmufl N, Fiahin M, Dogru T, et al. The effectiveness of nurse-led telephone follow-up in patients with type 2 diabetes mellitus. Turkish Journal of Endocrinology and Metabolism. 2010;14(1):1–5.
  54. 54. Gonzalez JS, McCarl LA, Wexler DJ, Cagliero E, Delahanty L, Soper TD, et al. Cognitive-behavioral therapy for adherence and depression (CBT-AD) in type 2 diabetes. Journal of Cognitive Psychotherapy. 2010;24(4):329–43. pmid:2011-09229-007.
  55. 55. Tang TS, Funnell MM, Brown MB, Kurlander JE. Self-management support in "real-world" settings: An empowerment-based intervention. Patient Education and Counseling. 2010 May;79(2):178–84. pmid:2010-07961-009.
  56. 56. Wolever RQ, Dreusicke M, Fikkan J, Hawkins TV, Yeung S, Wakefield J, et al. Integrative health coaching for patients with type 2 diabetes: A randomized clinical trial. Diabetes Educator. 2010;36(4):629–39. pmid:20534872
  57. 57. Zhang Y, Lave JR, Donohue JM, Fischer MA, Chernew ME, Newhouse JP. The impact of medicare part D on medication adherence among older adults enrolled in medicare-advantage products. Medical Care. 2010;48(5):409–17. pmid:20393360
  58. 58. Garcia-Huidobro D, Bittner M, Brahm P, Puschel K. Family intervention to control type 2 diabetes: A controlled clinical trial. Family Practice. 2011 Feb;28(1):4–11. pmid:2011-01781-002.
  59. 59. Khan MA, Shah S, Grudzien A, Onyejekwe N, Banskota P, Karim S, et al. A diabetes education multimedia program in the waiting room setting. Diabetes Therapy. 2011;2(3):178–88. pmid:22127826
  60. 60. Mehuys E, Van Bortel L, De Bolle L, Van Tongelen I, Annemans L, Remon JP, et al. Effectiveness of a community pharmacist intervention in diabetes care: A randomized controlled trial. Journal of Clinical Pharmacy and Therapeutics. 2011;36(5):602–13. pmid:21143256
  61. 61. Mitchell B, Armour C, Lee M, Song YJ, Stewart K, Peterson G, et al. Diabetes Medication Assistance Service: the pharmacist's role in supporting patient self-management of type 2 diabetes (T2DM) in Australia. Patient Educ Couns. 2011 Jun;83(3):288–94. pmid:21616627.
  62. 62. Piette JD, Richardson C, Himle J, Duffy S, Torres T, Vogel M, et al. A randomized trial of telephonic counseling plus walking for depressed diabetes patients. Medical Care. 2011 Jul;49(7):641–8. pmid:2011-13139-005.
  63. 63. Ramanath KV, Santhosh YL. Impact of clinical pharmacist provided patient education on QOL outcome in type II diabetes mellitus in rural population. Asian Journal of Pharmaceutical and Clinical Research. 2011;4(4):15–20.
  64. 64. Shetty AS, Chamukuttan S, Nanditha A, Raj RKC, Ramachandran A. Reinforcement of adherence to prescription recommendations in Asian Indian diabetes patients using short message service (SMS)-a pilot study. Journal of Association of Physicians of India. 2011;59(11):711–4.
  65. 65. Smith S, Paul G, Kelly A, Whitford D, O'Shea E, O'Dowd T. Peer support for patients with type 2 diabetes: Cluster randomised controlled trial. BMJ: British Medical Journal. 2011 Feb;342(7795):No Pagination Specified. pmid:2011-06060-002.
  66. 66. Wakefield BJ, Holman JE, Ray A, Scherubel M, Adams MR, Hillis SL, et al. Effectiveness of home telehealth in comorbid diabetes and hypertension: a randomized, controlled trial. Telemedicine journal and e-health: the official journal of the American Telemedicine Association. 2011;17(4):254–61. pmid:21476945
  67. 67. Walker EA, Shmukler C, Ullman R, Blanco E, Scollan-Koliopoulus M, Cohen HW. Results of a successful telephonic intervention to improve diabetes control in urban adults: a randomized trial. Diabetes Care. 2011 Jan;34(1):2–7. pmid:21193619.
  68. 68. Barron JJ, Cai Q, Turner RM, White JT, Amirpoor LW. Analyzing the impact of different value-based insurance design programs. American Journal of Pharmacy Benefits. 2012;4(1):29–36.
  69. 69. Bogner HR, Morales KH, de Vries HF, Cappola AR. Integrated management of type 2 diabetes mellitus and depression treatment to improve medication adherence: a randomized controlled trial. Annals of family medicine. 2012;10(1):15–22. pmid:22230826
  70. 70. Brennan TA, Dollear TJ, Hu M, Matlin OS, Shrank WH, Choudhry NK, et al. An integrated pharmacy-based program improved medication prescription and adherence rates in diabetes patients. Health Aff (Millwood). 2012 Jan;31(1):120–9. pmid:22232102.
  71. 71. Choi SE, Rush EB. Effect of a short-duration, culturally tailored, community-based diabetes self-management intervention for Korean immigrants: A pilot study. The Diabetes Educator. 2012 May;38(3):377–85. pmid:2012-13233-008.
  72. 72. Farmer A, Hardeman W, Hughes D, Prevost AT, Kim Y, Craven A, et al. An explanatory randomised controlled trial of a nurse-led, consultation-based intervention to support patients with adherence to taking glucose lowering medication for type 2 diabetes. BMC family practice. 2012;13:30. pmid:22480341
  73. 73. Kroese FM, Adriaanse MA, T. Boosters, anyone? Exploring the added value of booster sessions in a self-management intervention. Health Education Research. 2012;27(5):825–33. pmid:2011688559.
  74. 74. Mellitus Janice C- M, Christopher L E, Bryan C B, Debra B, Camela S M, Daphne S. A Culturally Targeted Self Management Program for African Americans With Type 2 Diabetes Mellitus. Canadian Journal of Nursing Research. 2012;44(4):126–41. pmid:2011891755.
  75. 75. Odegard PS, Christensen DB. MAP study: RCT of a medication adherence program for patients with type 2 diabetes. J Am Pharm Assoc (Wash). 2012;52(6):753–62. pmid:23229961
  76. 76. Ramanath KV, Bhanuprakash M, Nagakishore CH, Mahesh Kumar S, Balaji DBSS. Study the clinical phamacist influence on medication adherence & quality of life of rural type-2 diabetes mellitus patients in a tertiary care hospital. Archives of Pharmacy Practice. 2012;3(2):170–80.
  77. 77. Vervloet M, van Dijk L, Santen-Reestman J, van Vlijmen B, van Wingerden P, Bouvy ML, et al. SMS reminders improve adherence to oral medication in type 2 diabetes patients who are real time electronically monitored. International Journal of Medical Informatics. 2012;81(9):594–604. pmid:22652012
  78. 78. Zolfaghari M, Mousavifar SA, Pedram S, Haghani H. The impact of nurse short message services and telephone follow-ups on diabetic adherence: Which one is more effective? Journal of Clinical Nursing. 2012;21(13–14):1922–31.
  79. 79. Greenapple R. Review of strategies to enhance outcomes for patients with type 2 diabetes: Payers' perspective. American Health and Drug Benefits. 2011;4(6):377–86. pmid:25126364
  80. 80. Barnard K, Peyrot M, Holt R. Psychosocial support for people with diabetes: past, present and future. Diabetic Medicine. 2012;29(11):1358–60. pmid:22681530
  81. 81. Cha E, Yang K, Lee J, Min J, Kim KH, Dunbar SB, et al. Understanding cultural issues in the diabetes self-management behaviors of Korean immigrants. The Diabetes Educator. 2012;38(6):835–44. pmid:23019236
  82. 82. Kim G, Ford KL, Chiriboga DA, Sorkin DH. Racial and ethnic disparities in healthcare use, delayed care, and management of diabetes mellitus in older adults in California. Journal of the American Geriatrics Society. 2012;60(12):2319–25. pmid:23194086
  83. 83. Richard L Street Jr. WRG, Timothy Manning. Health Promotion and Interactive Technology: theoritical applications and future directions1997.
  84. 84. Glasgow RE, McKay HG, Piette JD, Reynolds KD. The RE-AIM framework for evaluating interventions: what can it tell us about approaches to chronic illness management? Patient education and counseling. 2001;44(2):119–27. pmid:11479052
  85. 85. Campbell M, Fitzpatrick R, Haines A, Kinmonth AL, Sandercock P, Spiegelhalter D, et al. Framework for design and evaluation of complex interventions to improve health. BMJ: British Medical Journal. 2000;321(7262):694. pmid:10987780
  86. 86. Noar SM, Benac CN, Harris MS. Does tailoring matter? Meta-analytic review of tailored print health behavior change interventions. Psychological bulletin. 2007;133(4):673. pmid:17592961
  87. 87. Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabetic Medicine. 2015.
  88. 88. Gallant MP. The influence of social support on chronic illness self-management: a review and directions for research. Health Education & Behavior. 2003;30(2):170–95.
  89. 89. Association AD. Economic costs of diabetes in the US in 2007. Diabetes care. 2008;31(3):596–615. pmid:18308683
  90. 90. Gambert SR, Pinkstaff S. Emerging Epidemic: Diabetes in Older Adults: Demography, Economic Impact, and Pathophysiology. Diabetes Spectrum. 2006;19(4).
  91. 91. Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock SJ, Wines RC, et al. Interventions to Improve Adherence to Self-administered Medications for Chronic Diseases in the United StatesA Systematic Review. Annals of internal medicine. 2012;157(11):785–95. pmid:22964778