Diabetes mellitus (DM) is a major global health concern, with an increasing prevalence worldwide, particularly in low- and middle-income countries like Bangladesh. In 2020, the global prevalence of diabetes was estimated to be 9.3%, and this number is expected to rise to 10.2% by 2045 [1]. In Bangladesh, the increasing incidence of diabetes is linked to lifestyle changes, urbanization, and an aging population, with studies estimating that over 8 million people are affected by the disease [2]. The management of diabetes often involves polypharmacy, as patients are commonly prescribed multiple drugs to control blood glucose, manage comorbidities, and prevent complications. Common drugs include oral hypoglycemic agents, insulin, antihypertensive medications, and lipid-lowering agents [3]. However, the use of multiple medications in diabetic patients increases the risk of drug-drug interactions (DDIs), which can have significant implications for patient safety. DDIs occur when one drug alters the pharmacokinetic or pharmacodynamic properties of another, potentially leading to diminished therapeutic effects, increased toxicity, or adverse drug reactions (ADRs). There are two primary types of DDIs: pharmacokinetic and pharmacodynamic interactions. Pharmacokinetic interactions involve changes in drug absorption, distribution, metabolism, or excretion, while pharmacodynamic interactions involve changes in the drug's action at the site of action, such as altering glucose metabolism or blood pressure regulation [4]. Diabetic patients are often at higher risk for DDIs due to the presence of other comorbidities, such as hypertension, dyslipidemia, and cardiovascular diseases, which require additional medications [5]. The simultaneous use of multiple medications for these conditions increases the likelihood of potentially harmful interactions. Certain drug combinations, such as the use of sulfonylureas with beta-blockers or metformin with angiotensin-converting enzyme (ACE) inhibitors, have been identified as high-risk for DDIs [6]. These interactions can lead to issues such as hypoglycemia, altered blood pressure control, and other adverse outcomes, especially when drugs affect the same physiological pathways [7]. Despite the importance of identifying and preventing DDIs, there is limited research in Bangladesh regarding the prevalence and patterns of DDIs in diabetic patients. Previous studies from other countries have highlighted the frequency of DDIs in diabetic patients and the need for careful medication management [8,9]. In Bangladesh, however, the information regarding the patterns of potential DDIs in diabetic patients remains scarce. With increasing numbers of patients being treated for diabetes and its complications, the management of DDIs becomes crucial in clinical practice [10]. This study aimed to evaluate the pattern of potential DDIs in diabetic patients at a tertiary care teaching hospital in Bangladesh. The results will help identify commonly occurring DDIs, their potential risks, and the associated clinical outcomes. Understanding these interactions is essential for healthcare professionals to optimize diabetes management, prevent adverse outcomes, and improve patient safety.

This cross-sectional study was conducted at Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2022 to December 2022.  The study enrolled 63 diabetic patients through purposive sampling. Inclusion criteria included patients aged 18 years and above, diagnosed with type 2 diabetes mellitus, and currently undergoing pharmacological treatment for diabetes management. Patients with incomplete medical records or those who were unable to provide consent were excluded. Data were collected from the hospital’s outpatient and inpatient departments. A detailed patient history was taken, including demographic information, medical history, current medications, and comorbid conditions. The medications prescribed were reviewed for potential drug-drug interactions (DDIs) using established drug interaction databases and references. The DDIs were categorized into major, moderate, or minor based on their clinical significance and the severity of the interaction. The data were analyzed using MS Office tools, where descriptive statistics were used to summarize the demographics and medication profiles of the participants. The frequency and types of potential DDIs were analyzed and categorized by the drug classes involved. Ethical approval for the study was obtained from the hospital’s ethical review committee, and informed consent was obtained from all participants prior to data collection.

In this study, 63 diabetic patients were included, with a mean age of 55.2±9.4 years, ranging from 35 to 75 years. Among the participants, 70% were male, and 30% were female. The majority of patients (54%) were aged 50-59 years, while 46% were aged 60 years and above. The demographic characteristics of the study participants are presented in Table 1. The most commonly prescribed drugs among the patients were oral hypoglycemic agents (58%), followed by antihypertensive medications (48%) and statins (42%). Table 2 illustrates the distribution of medications prescribed to the study participants. Potential drug-drug interactions (DDIs) were identified in 35 patients (55.6%). A total of 45 potential DDIs were observed. The majority of DDIs were classified as moderate (56%), followed by major (34%) and minor (10%) interactions. Table 3 presents the distribution of DDIs by severity. Table 4 shows the most common drug combinations that led to potential DDIs. The combination of metformin and angiotensin-converting enzyme inhibitors (ACEIs) was the most frequent (12%). Other common drug pairs included sulfonylureas and beta-blockers (9%), and statins with calcium channel blockers (8%). Regarding the pharmacodynamic nature of the interactions, the most frequent interactions involved the combined use of antihypertensive medications and oral hypoglycemic agents (20%), followed by combinations of statins with antihypertensive drugs (18%). Table 5 summarizes the types of pharmacodynamic interactions.

Table 1: Demographic Characteristics of Study Participants

Table 2: Distribution of Medications Among Study Participants

Table 3: Distribution of DDIs by Severity

Table 4: Most Common Drug Combinations Leading to DDIs

CCB: Calcium Channel Blockers

Table 5: Distribution of Pharmacodynamic Interactions by Drug Classes

OH: Oral Hypoglycemic, LLA: Lipid-lowering Agent

This study highlights the significant prevalence of potential drug-drug interactions (DDIs) in diabetic patients, with 55.6% of participants experiencing a total of 45 DDIs. Most interactions were moderate in severity, followed by major and minor interactions. The findings align with previous research that has demonstrated the high incidence of DDIs in patients with diabetes, particularly due to polypharmacy and the complex nature of managing diabetes and its comorbidities [11,12]. Diabetes mellitus is often accompanied by other chronic conditions such as hypertension, dyslipidemia, and cardiovascular diseases, all of which require long-term medication management. The combination of multiple drugs increases the risk of potential DDIs, which can adversely affect treatment outcomes and patient safety [13,14]. The most common drug combinations in this study involved metformin with angiotensin-converting enzyme inhibitors (ACE inhibitors), sulfonylureas with beta-blockers, and statins with calcium channel blockers. These findings are consistent with studies that have reported similar drug combinations leading to potential DDIs in diabetic patients [15,16]. Metformin and ACE inhibitors, for example, are frequently used together in managing diabetes and hypertension, yet this combination can lead to an increased risk of renal dysfunction and hypotension [17]. Similarly, the concurrent use of sulfonylureas and beta-blockers may lead to masked hypoglycemic symptoms, which can complicate the management of blood glucose levels [18]. Moderate interactions were the most common in this study, which suggests that while the risk of severe adverse outcomes may be lower, there is still a considerable need for intervention to prevent the cumulative effects of multiple moderate interactions. This aligns with findings from other studies, which emphasize the need for appropriate drug monitoring to identify and address potential DDIs before they cause harm [19,20]. Furthermore, drug interactions may not always lead to immediate clinical symptoms, making it essential for healthcare providers to be proactive in identifying interactions during routine medication reviews. The study also underscores the importance of implementing clinical decision support systems (CDSS) and improving patient education on the risks of drug interactions. CDSS can help healthcare providers identify potential DDIs during prescribing and dispensing, thus reducing the risk of adverse drug events [22,22].  Patient education can also play a crucial role in improving medication adherence and ensuring that patients are aware of the signs and symptoms of potential interactions. Despite the important insights gained from this study, it has some limitations. The study was conducted at a single center, which may limit the generalizability of the findings to other healthcare settings. Additionally, only potential DDIs were considered, and actual clinical outcomes were not assessed. Future research should explore the impact of DDIs on patient outcomes and investigate interventions to mitigate these risks.

Limitations:

This study has several limitations. It was conducted at a single tertiary care hospital, limiting its generalizability to other settings. Additionally, only potential drug-drug interactions (DDIs) were assessed, without evaluating their actual clinical impact. A larger, multi-center study assessing clinical outcomes would provide more comprehensive insights.

The study reveals a high prevalence of potential drug-drug interactions (DDIs) among diabetic patients, with the majority of interactions being moderate in severity. The most common drug combinations involve oral hypoglycemic agents, antihypertensive medications, and statins. These findings highlight the importance of monitoring drug regimens in diabetic patients to reduce the risk of adverse effects and optimize treatment outcomes, emphasizing the need for heightened awareness and precaution in managing medications for this population.

Recommendations:

It is recommended that healthcare providers regularly review medication regimens in diabetic patients to identify and manage potential drug-drug interactions. Additionally, implementing clinical decision support systems, improving patient education on medication adherence, and encouraging regular follow-up visits can help minimize the risk of DDIs and enhance therapeutic efficacy. 

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