Diabetes is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion and/or action, causing long-term organ damage, and thus requires proper management to control the disease state and slow down the progression towards microvascular and macrovascular complications (1). It is one of the most challenging public health problems in the 21^st century being one of four priority noncommunicable diseases targeted for action by world leaders. Approximately 537 million adults, constituting 10.5% of the global adult population, are currently living with diabetes, reflecting a prevalence of 1 in 10 individuals. Projections indicate that this number is anticipated to increase to 643 million by the year 2030 and further escalate to 783 million by 2045 (2).majority of it being type 2 diabetes. Over the past decade, diabetes prevalence has risen faster in low- and middle-income countries than in high-income countries (3).

Effective diabetes management involves appropriate dietary intake, exercise, and adhering to necessary medication regimens. Large, population-based, prospective trials have shown that intensive glucose management can dramatically decrease the rate of microvascular complications in diabetes mellitus as well as protect against macrovascular complications to some degree (4, 5). According to the American Diabetes Association recommendation, a reasonable glycosylated hemoglobin (HbA1c) goal for many nonpregnant adults is <7% (6).

High HbA1c levels have consistently proven to be associated with increased risk of morbidity and mortality in long-term studies (7–10). Poorly controlled diabetes increases the risk of heart attack, stroke, kidney failure, leg amputation, vision loss, nerve damage, and dying prematurely. Its complications are resulting in increasing disability, reduced life expectancy and enormous health costs for virtually every society through direct medical costs and loss of work and wages (3, 10–12).

Despite this evidence and the many advances in diabetes care, 33–49% of patients still do not meet targets for glycemic, blood pressure, or cholesterol control (6, 13, 14). This is the case in Africa where a large number of people with diabetes do not reach the recommended HbA1c targets; likely due to a limited access to adequate health services, low diabetic knowledge, and a high prevalence of drug therapy problems (15–18).

Drug therapy problems are a consequence of a patient’s drug-related needs that have gone unmet. A drug therapy problem is any undesirable event experienced by a patient that involves, or is suspected to involve drug therapy, and that interferes with achieving the desired goals of therapy (19). It is central to pharmaceutical care practice (19–22). Drug therapy problems may lead to increased morbidity, mortality, healthcare costs, and recurrent hospital admissions and prolonged hospitalization (23). A systematic review indicated that drug-related problems account for more than 15.4% of hospital admissions and 2.7% death rate (24).

Patients with diabetes are at risk of drug therapy problems as they are receiving multiple medications, which can happen at any step during the treatment process and it affects the therapeutic outcome (17, 25). Studies done in Eastern Ethiopia and South-East Ethiopia reported that 64.2% and 88% of the study participants had at least one drug therapy problem with poor glycemic control (26, 27). An average of 1.8 drug therapy problems per patient were identified in Eastern Ethiopia (25).

A proactive approach to prevent, identify and resolve drug therapy problems is required in order to realize the best possible outcomes from drug therapy. Involvement of clinical pharmacists as a member of the healthcare team helps in identification and prevention of clinically significant drug therapy problems (28–30). In Brazil, pharmacist intervention increases compliance, reduces drug therapy problems and, consequently, improves glycemic control among patients with type 2 diabetes (31). In India, clinical pharmacists had a crucial role in minimizing drug related problems among diabetic patients with co-existing hypertension (1). In Addis Ababa Ethiopia, provision of medication therapy management services had a potential to reduce drug therapy problems and improve the clinical parameters (32).

The prevalence of drug therapy problems and associated factors varies between different populations ranging from 42% to 99.5% (25, 33); thus, a comprehensive data showing the magnitude of the problem and identifying specific risk factors is urgently needed for targeting interventions most effectively. Therefore, the aim of this review is to investigate the pooled prevalence of drug therapy problems and contributing factors among patients with diabetes mellitus.

This is a pioneer systematic review and meta-analysis study done in Ethiopia that examined the overall pooled estimates of prevalence of unmet drug related need of diabetic patients alongside with the frequently encountered types of drug therapy problems. In addition, this study explored multiple factors that are either positively or negatively associated with unmet drug related needs of diabetic patients in Ethiopia.

The pooled prevalence of unmet drug-related needs of diabetic patients in Ethiopia was 74%. This eye-opening finding is higher than a general prevalence of drug therapy problems in Ethiopian public health institutions 69.4% (51). The disparities between the prevalence rates in specific diabetic populations compared to the general public health institutions shed light on the need for targeted interventions. Tailored initiatives should be implemented to address the unique challenges faced by diabetic patients, aiming to improve medication accessibility, affordability, and overall healthcare delivery. Finding from this meta-analysis is lower from a report of recent global systematic review study (52) pooled from 20 observational studies done on hospitalized type-2 diabetic patients that reported an overall prevalence of 7% to 94% of drug related problems (DRPs). The incongruency could be possibly ascribed to difference in characteristics of study population, where ours pooled studies that were conducted on all types of DM patients who are both ambulatory and/or hospitalized while the ecumenical study was done only in type-2 DM patients who are hospitalized in medical wards. Besides, it could also be linked to variation in methods (chart reviews, incident reports, surveys, direct observation, interviews) implemented to identify DRPs in the included studies as each method is endowed with varying potential and rate of detecting DRPs. In this study, the pooled mean of unmet drug-related need per patient in diabetic patients in Ethiopia was 1.45. This finding sheds light on the prevalent challenges in meeting the medication requirements of diabetic individuals in the Ethiopian setting which underscores the importance of addressing the gaps in drug therapy to enhance the overall management and outcomes for patients with diabetes.

Concerning the specific type of drug therapy problem attested, patients with additional drug therapy needs exhibited the highest proportion (25%) while high dose drug therapy problem displayed a relatively lower proportion (4%). This could be an indicative of lack of adherence to standard treatment guideline, uncoordinated work between prescribers and clinical pharmacists, and poor patient counseling service. In view of our finding, the result of a similar study (52) done elsewhere demonstrated that the most common DRPs experienced by type-2 DM patients were drug-drug interactions (DDIs) [29% to 94%], adverse drug reactions (ADRs) [46.4%], therapeutic effectiveness problems [50.6%], and inappropriate medication use [55.2%]. However, from a theoretical perspective, drug-drug interaction is not regarded as a specific type of DRP rather a cause for most types of DRPs such as dose too high, dose too low, ADRs, and ineffective drug therapy problem. By following a systematic approach to identify and discontinue medications in which potential harm preponderate the benefit and medications with ill-defined benefit, it is possible to abridge exposure to DRPs.

The sub-group analysis of this study indicated that about 79% of unmet drug-related need were reported in type-2 DM patients, 82% were accounted from observational studies that employed retrospective study designs, and 82% were from studies conducted in Harar, Ethiopia. So far, comprehensive reviews have not been done anywhere in relation to study setting, and study designs. However, in terms of study characteristics, this finding is in conformity to a nascent similar study which found a 7% to 94% unmet drug related needs solely in type-2 DM patients (52).

According to this study, the use of multiple medications, advanced age, the presence of comorbidities, and an extended duration of illness were the most frequently reported factors associated with unmet drug related need of patients with diabetes while taking insulin monotherapy and having history of hospitalization were found to have a lower risk of facing unmet drug-related needs. Consonant to our study, a nascent systematic review and meta-analysis study (52) done solely on hospitalized type-2 DM patients unveiled that the presence of comorbidities and ingestion of antihypertensive medications enhances exposure to DRPs, possibly due to increasing multiple drug therapy and drug-drug interaction. Thus, to successfully prevent DRPs early in DM patients, thorough review of patients’ medical illness and treatment protocols should be accomplished to encourage appropriate prescribing of medications. A qualitative survey compiled from Brazil, China, and Russia on unmet needs of type-2 DM patients reported more information and support regarding food and diet (36%), designing novel solution to monitor blood glucose levels such as non-invasive devices (36%) and boosting awareness about type-2 DM and its treatment protocols (26%) (53). These recommendations help to fulfil the drug related needs of diabetic patients and thereby decrease the occurrence of both actual and potential drug related problems.

One crucial aspect that emerged during our analysis was the substantial heterogeneity among the included studies, as indicated by a high I² value of 99.0% and a p-value less than 0.001. The utilization of a weighted inverse variance random-effects model did not adequately address this variability. In our effort to better understand and address the heterogeneity, we employed a forest plot for subjective assessment, revealing the diverse nature of the individual study estimates. To further explore the potential sources of heterogeneity, we conducted a subgroup analysis and univariate meta-regression, considering sample size and study period as variables. The results, with respective tau-squared values of 0.2375 (P=0.355) and 0.2364 (P=0.452), suggested that neither sample size nor study period significantly contributed to the observed heterogeneity. This implies that other factors, not explicitly explored in this study, might be influencing the variations among the included studies.

This pioneering research in the Ethiopian context marks the first attempt to establish pooled prevalence estimates of unmet drug-related needs among diabetic patients, alongside an exploration of contributing factors. It stands out as a groundbreaking global study that comprehensively reviews existing literature on drug-related needs, encompassing both ambulatory and hospitalized diabetic patients across various types of diabetes. However, it is crucial to acknowledge certain limitations. The study reveals significant heterogeneity between the included studies, as indicated by the I² statistic. Additionally, the presence of publication bias is noteworthy constraints within the scope of this research.

A considerable proportion of diabetic patients in Ethiopia face significant unmet drug-related needs, with the most prevalent issue being ineffective drug therapy. Factors such as the use of multiple medications, advanced age, the presence of comorbidities, and prolonged illness duration contribute to an elevated risk of experiencing unmet drug-related needs among diabetic patients. Consequently, healthcare professionals, especially prescribers, should be mindful of these factors to proactively prevent unmet drug-related needs in individuals with diabetes. To develop practical strategies for identifying, addressing, and preventing drug-related problems, future studies in this area are imperative. Clinical pharmacists stationed in medical wards and outpatient departments can play a vital role by efficiently identifying, classifying, and resolving drug-related problems through collaborative efforts with other healthcare professionals. This collaborative approach aims to enhance patient clinical outcomes and overall diabetes management.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

MG: Conceptualization, Formal analysis, Methodology, Supervision, Validation, Writing – original draft, Writing – review & editing. NT: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. TS: Conceptualization, Data curation, Methodology, Writing – original draft, Writing – review & editing. MD: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. TW: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. YB: Data curation, Methodology, Writing – original draft, Writing – review & editing. AB: Methodology, Supervision, Writing – original draft, Writing – review & editing. MH: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing.