Factors influencing medication adherence in co-morbid hypertension and diabetes patients: A scoping review

Introduction Interest in medication adherence has expanded significantly, especially in relation to the management of hypertension or diabetes in recent years. A scoping review that focuses on medication adherence in the co-morbidity of hypertension and diabetes provides crucial guidance for effective management of these interrelated diseases. Aim To conduct a scoping review of factors associated with medication adherence among individuals with co-morbid hypertension and diabetes. Methods The evaluation was conducted in accordance with the PRISMA-ScR guidelines to ensure the quality of the study. We searched three databases (Scopus, CINAHL, Medline) and one search engine (Google Scholar) from April 2023 to July 2023 on studies related to medication adherence in co-morbid hypertension and diabetes. Except for reviews there were no restrictions on design, location, and time of study. Results In total, 972 studies that were not duplicated were obtained. After eligibility and screening procedures were completed, 31 articles were ultimately included in the scoping review. Medication adherence was significantly affected by patient, condition, therapy, socio-economic and health related factors. Intervention trials revealed that education and counselling by pharmacists, nurses, physicians, diabetes educators, community health workers and the use of telephone to motivate patients significantly improved medication adherence. Conclusion This review shows the intricate factors influencing medication adherence in patients with co-morbid hypertension and diabetes, emphasizing the need for tailored interventions involving healthcare professionals, policymakers, and researchers.


Introduction
The co-occurrence of hypertension and diabetes is a serious public health burden. 1,2Globally, co-morbidity is alarmingly prevalent, with statistics estimating that over 40% of patients with diabetes also suffer from hypertension. 1,3This dual burden is especially apparent in older persons, underlining the challenges posed by an aging population. 4,5hese chronic diseases are related with an increased risk of cardiovascular disease, renal failure, stroke, and high mortality. 1,2,6Diabetes and hypertension co-occurrence increases cardiovascular risk synergistically. 1,7Underlying the mechanisms of this connection are intricate networks of vascular dysfunction, insulin resistance, inflammation, and oxidative stress.Co-morbid patients are more likely to develop atherosclerosis, endothelial dysfunction, and left ventricular hypertrophy, which increases their susceptibility to adverse cardiac events 8,9 .Co-morbid hypertension and diabetes have substantial economic and societal implications that transcend individual health. 2,10The need for medical services, hospitalizations, and long-term care has soared because of these co-morbidities.The financial burden is exacerbated by the need for sophisticated treatment regimens, frequent physician visits, and high medications costs. 10,11ypertension and diabetes co-morbidity present various hurdles that negatively impact medication adherence. 12,13The necessity of managing two chronic diseases imposes additional cognitive and logistical pressures on patients, resulting in frequent medication nonadherence. 13,14Controlling blood pressure and blood glucose simultaneously can result in regimens that are so complex as to be overwhelming for patients.The progression of a disease and its prognosis are significantly impacted by drug adherence.In co-morbid patients, poor adherence can raise the risk of cardiovascular events, renal issues, and microvascular damage.Nonadherence disrupts blood pressure and glucose regulation, reducing the therapeutic efficacy of medications and increasing the chance of side effects. 15,16This exposes patient to increased symptom burden and diminished quality of life. 17,18edication adherence not only affects physiological parameters, but also improves patients' overall quality of life.Blood pressure and glucose levels that are well-managed contribute to reduced symptoms, enhanced energy, and improved mental health. 19,20edication adherence is a pillar of effective illness treatment in the complex context of hypertension and diabetes co-morbidity. 16,21The interaction between these diseases needs a rigorous and thorough treatment strategy, with the patient bearing responsibility for drug adherence.A scoping review concentrating on medication adherence in hypertension and diabetes co-morbidity serves as a key compass for navigating the intricacies of these intertwined illnesses.

Study design
A scoping review was done using the methodological approach proposed by Arskey and O'Malley and advanced by Levac et al. 22 The sixstep methodology included: a) identification of research questions; which is typically broad in scope b) identification of relevant research articles; c) selection of studies; including the development of criteria for inclusion and exclusion, predicated on a competence in the field of literature d) data charting and synthesis; involving the sifting, sorting, and charting of information in accordance with significant issues and themes e) summary, discussion, and analysis; this stage yields a thematic analysis and a descriptive and numerical summary of the data; and f) discussions with stakeholders; Is a consultation exercise, which involves key stakeholders in order to validate and inform the study findings.Since this review did not involve external stakeholders, the sixth phase, which included consultations with stakeholders, was not utilized.The scoping review was reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).The research team drafted the protocol (AOK and IAK).All steps of study selection were conducted by two independent reviewers, with consensus meetings serving as tiebreakers to ensure that all eligibility criteria were properly applied.

Identification of research questions
The primary objectives were to identify factors related to medication adherence, instruments for evaluating adherence, categorize strategies for promoting medication adherence, and assess their outcomes.This process was guided by the following research questions: 1.What are the key factors that influence medication adherence in patients with comorbid hypertension and diabetes?2. Which measures are used in the evaluation of medication adherence in patients with co-morbid hypertension and diabetes?3. How can medication adherence strategies be categorized based on their approach or intervention type in comorbid hypertension and diabetes?4. What are the outcomes associated with various strategies employed to promote medication adherence?

Identification of relevant research articles
From April to July 2023, three databases (Scopus, Medline and CINAHL) and one search engine (Google Scholar) were searched.This review was based on studies conducted on medication adherence in comorbid hypertension and diabetes with no restriction on location and time of study.The search terms used four main keywords: "comorbidity", "medication adherence" and "hypertension and diabetes".They were combined using Boolean Operator (AND, OR, NOT).Medical subject subheading (MeSH) terms were used for the search in Scopus, Medline, and CINAHL.The final search terms used in SCOPUS were as follows."Medication AND adherence", "comorbidity OR multimorbidity", "hypertension AND diabetes", In MEDLINE MH "Medication Adherence+") OR (MH "Patient Compliance+"), (MH "Comorbidity+") OR "comorbidity" OR (MH "Multimorbidity"), "Hypertension and diabetes" OR (MH "Diabetes Mellitus+") OR (MH "Diabetes Mellitus, Type 2+") and in CINAHL "medication adherence," "comorbidity" or "multimorbidity" "hypertension and diabetes".
Inclusion criteria involved documents that were 1) authored in English, 2) peer-reviewed and literature-indexed to ensure quality, 3) concentrated on patients with hypertension and diabetes co-morbidities and 4) presented systematically with well-described medication adherence measures.Studies that did not have an abstract during the screening phase or the full-text version during the eligibility step (after direct contact with the authors) were excluded.There were no research type or design-based exclusions except for reviews.

Selection of studies
Two members of the research team (AOK and IAK) evaluated the eligibility of each paper independently.The evaluation was conducted procedurally with a screening of the title and abstract followed by a screening of the whole text (Fig. 1).Disagreements over the eligibility of an article for inclusion in the review were resolved through discussion.

Quality assessment of the included studies
Two researchers (AOK, IAK) assessed the quality of the included studies independently using the applicable critical evaluation checklists from the Joanna Briggs Institute(JBI) to evaluate the methodological quality of the eligible studies.When there were discrepancies, two other reviewers were consulted (PP, KB).Four quality assessment methods from the Joanna Briggs Institute Tools were utilized for randomized control trial, cross-sectional analytical research, cohort studies and qualitative investigations Table 1.For the randomized control trial assessment, thirteen domains were evaluated as "Yes (present), No (absent), Unclear (insufficient information), or Not Applicable."The cross-sectional assessment of analytical quality, eight domains were evaluated as "Yes (present), No (absent), Unclear (insufficient information), or Not Applicable."The qualitative studies checklist consists of ten dimensions scored as "Yes" (present), "No" (missing), "Unclear" (insufficient information), or "Not Applicable".Similarly, the checklist for cohort studies consists of eleven items that are scored as Yes (present), No (absent), Unclear (insufficient data), or Not Applicable.The checklist criteria were not altered, but they were interpreted in a flexible manner to reflect our emphasis on the medication adherence in comorbid hypertension and diabetes patients.

Data charting and synthesis
The following information were extracted from each study using a standardized data extraction form: study title, authors, primary affiliation of author, year, study design, study settings, methods, country of study, study focus, factors affecting adherence (categorized as healthrelated factors, clinical condition-related factors, therapy-related factors, patient-related factors, and socio-economic factors), adherence measures, tools for medication adherence, study limitations, and recommendations.

Collating, summarizing, and reporting results
The findings were reported following the review questions, including information on prevalence, adherence evaluation, associated factors, and interventions relating to medication adherence in patients with comorbid hypertension and diabetes.In reporting the data, implications for pharmaceutical care, clinical practice, and policy were also highlighted.

Study characteristics
The database searches revealed 1123 potentially relevant studies.After removing duplicates, 972 articles were examined.Following the screening of titles and abstracts, 43 full-text papers were chosen.31 papers were considered for analysis after the eligibility criteria were applied to the full-text articles(Fig.1).Included among 31 papers were randomized controlled trials/intervention studies, 2 cohort studies, qualitative studies and 22 cross-sectional studies.Regarding the article's country of origin, 7 investigations were conducted in the United States, in India, 4 in Ghana, 3 in Nigeria, 2 in Mexico, and 1 each in Indonesia, Sri Lanka, Canada, Saudi Arabia, Poland, Italy/Poland, Malaysia, Brazil, and Colombia (Table 1).

Factors associated medication adherence in co-morbid hypertension and diabetes
The factors associated with medication adherence in individuals with co-morbid hypertension and diabetes were categorized into healthrelated factors, condition related factors, therapy related factors, patient related factors and socio-economic related factors, as outlined below (Table 2):

Health-related factors
Health related factors included the nurses involved in home telehealth intervention, 23 patients who receive care from the same physician for both conditions and prescribe statins frequently, 24 physician involved in home telehealth intervention, 23 a certified diabetes educator, 23 pharmacist education and counselling 21,25 ,pharmacist brief telephone intervention, 26 motivational interview by trained pharmacist student, 27 community healthcare workers intervention, 28 availability of medicine 29 out-patient clinic visits, 29,30 phone calls, 30 emails, 30 attendance to health center, 13 prolong duration of time for consultation, 31 poor prescription instruction by health providers 17 Provider patient relationship 29 and the health care professionals response to their concerns and difficulties respect to their treatment. 32

Socio-economic related factors
Health insurance, 30,36 lack of financial resources 13,46 , employment status 39,40 , societal norms, 17 social support, 29,32,47 monthly expenditure on medications, 16 Medication Costs 29 ,mode of payment for medical bills 35 , low income 39 ,economic resources to travel for consultation, have support from their families or close acquaintances, 32 family support through reminders 44 were the socio-economic factors associated with medication adherence among individuals with comorbid hypertension and diabetes.

Medication adherence measuring tools
There were 32 individually different tools used to measure adherence.Likewise, 29 studies used a single adherence measuring tool, study used two different tools, 1 study used three.The majority of studies employed self-reporting tools to assess medication adherence, with 21 studies exclusively relying on self-reporting tools as the sole measure of adherence outcomes.Proportion of days covered was the most frequent objective measurements of adherence (n = 5).Adherence levels ranged from as low as 7% to as high as 80%, reflecting the variability in patient adherence.

Intervention types and study outcomes in co-morbid hypertension and diabetes
The various interventions used to improve medication adherence included education and counselling by pharmacists, 21,25 telephone motivational intervention 26,27 , nurse, physician, and a certified diabetes educator counselling, 23 medication therapy management 38 and intervention by community health workers. 28Five included studies, 21,[25][26][27][28] reported that their interventions had a substantial positive effect on medication adherence.Nevertheless, 2 of the studies, 23,38 did not find any meaningful influence on any of the adherence outcomes that were examined.

Discussion
Due to the global health significance of co-morbid hypertension and diabetes 2 , this review incorporates papers from across various continents.Asia and America (including North and South America) are the primary contributors to this review, with United States of America 23,24,26,27,30,38,42 and India 29,31,41,44,46 contributing the most studies, respectively.The prevalence of medication adherence in patients with co-morbid hypertension and diabetes ranged from 7% to 80%. 26,30,38These variations could be because of many factors that influence medication adherence and differences in cultural settings that the studies were conducted. 50These factors include health care related, therapy related, condition related, patient related and socio-economic factors 51 .
The main health care related factors that influenced medication adherence was the involvement health care professionals in patient care 21,[23][24][25][26]38 and patient relationships with providers. 29 nadequate patient-provider relationships can lead to insufficient counselling and negatively affect patients' self-efficacy.50 Trust-based communication and effective discussion of adherence issues can improve patient selfefficacy and therapy adherence. Nelecting these factors can worsen disease severity.In terms of condition related factors co-morbidity 13,30,35 and complications 31,35 are significant factors associated with medication adherence, particularly in chronic illnesses like cardiovascular events, kidney failure, and neuropathy.These complications often require complex prescription regimens and lifestyle changes, which can overwhelm patients and lead to non-adherence.35 The cumulative impact of managing various health disorders can make it difficult to continuously adhere to recommended treatments.
Co-morbid hypertension and diabetes patients often require more prescribed medications, leading to increased medication-related burden. 16,20,52,53To address this, it is crucial to streamline treatment regimens, use combination medicines when suitable, and ensure patients receive sufficient knowledge about their condition and medication. 50,54Effective medication management requires a collaborative approach involving patients and healthcare practitioners. 38,55Adherence to prescribed medication can be influenced by side effects, medication interactions, and duration of therapy.These factors can be improved through continuous patient education, simplification of therapy, and fixed-dose combinations. 22ocio-economic factors that influence co-morbid patients' medication adherence is their access to health insurance, employment status, cultural beliefs, and social networks.Insufficient insurance coverage can hinder patients' ability to afford prescribed medications, leading to financial barriers. 56Support programs, insurance expansion, and reduced out-of-pocket costs can help alleviate these barriers. 57mployment-related obstacles can be mitigated through employersponsored health programs.Cultural ideas and societal conventions influence health behaviors, including medication adherence. 58The stigma associated with chronic illnesses might impede open dialogues on treatment and discourage the disclosure of such conditions.Promoting patient's adherence can be accomplished by the implementation of educational programs and culturally sensitive healthcare procedures that address these norms and concerns.Social support networks 59 and emotional encouragement from family, friends, or community groups can improve adherence.
Medication adherence is significantly influenced by patient specific factors such as gender, education level, and age.Healthcare professionals can improve health outcomes in managing chronic conditions like co-morbid hypertension and diabetes by implementing a patientcentered approach. 60Personalized educational interventions, clear communication, and regular assessments of patient comprehension are essential.Sustaining adherence requires prioritizing long-term benefits, addressing patient-specific concerns, and cultivating a positive quality of life. 45,616][27][28] Most interventions necessitate the patient's participation in decision-making pertaining to their condition.

Strength of the study
This review provides synthesized evidence of the current state of medication adherence studies with focus on the factors and interventions for patients with co-morbid hypertension and diabetes.The review contributes to evidence-based decision making and provides support for areas of practice that require further development.

Limitation of study
Though the current review utilized a transparent and rigorous methodology, it is not devoid of limitations.In this review three databases and one search engine was used for retrieving the documents and this might prevent other potential publications which may not have been indexed in such databases from being missed.Nevertheless, the deliberate omission of non-indexed literature ensured that the selection process was focused solely on peer-reviewed, minimally biased works.

Conclusion
Significant influences on medication adherence in co-morbid hypertension and diabetes patients were seen in relation to the patient, condition, therapy, socio-economic status, and health-related factors.Interventions designed to enhance adherence in individuals with comorbid hypertension and diabetes must consider the complex interaction of these factors.The implementation of customized interventions, which involve the cooperation of healthcare professionals, policymakers, and researchers, is critical to optimize medication adherence and, consequently, improve the health outcomes of patients.This review serves as a fundamental basis for formulating focused interventions and encouraging more scholarly investigations in this pivotal healthcare domain.Future studies should delve into the progression of adherence behaviors among individuals who are concurrently treated with hypertension and diabetes.Critical interventions to examine include the integration of digital health solutions, the investigation of shared decision-making processes, and the streamlining of complex medication regimens.Furthermore, gaining insight into the interaction between health policies and patient-reported outcomes will enhance the body of evidence and enable the optimization of treatments to achieve better results for patients who have co-morbid hypertension and diabetes.

Table 1
Summary of studies of medication adherence in patients with co-morbid hypertension and diabetes.
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Table 2
Description of factors associated with medication adherence in co-morbid hypertension and diabetes.