Assessment of Antidiabetic Drugs Utilization Patterns in Diabetic Patients with Nephropathy in a Tertiary Healthcare Facility

S. Aliyu et al., ISSN: 2814-1423 55 Nigerian Journal of Pharmaceutical and Biomedical Research Vol. 8 Issue.1 April, 2024. p-ISSN: 2579-1419 e-ISSN: 2814-1423 Assessment of Antidiabetic Drugs Utilization Patterns in Diabetic Patients with Nephropathy in a Tertiary Healthcare Facility Shuaibu Aliyu1*, Abdulkadir Umar Zezi2, Mohammad Garba Magaji2, and Fatima Bello3 1Department of Clinical Pharmacy and Pharmacy Practice, Ahmadu Bello University (ABU), Zaria – Nigeria 2Department of Pharmacology and Therapeutics, Ahmadu Bello University (ABU), Zaria – Nigeria 3Department of Medicine, Ahmadu Bello University (ABU), Zaria – Nigeria *Corresponding author, E-mail: [email protected], doi.org.10.55639/njpbr.1051.005 Abstract The presence of nephropathy in diabetic patients may complicate the management of diabetes. Appropriate use of drugs is essential in achieving optimal outcomes in such patients. Therefore, this study was aimed at assessing antidiabetic drugs utilization patterns in diabetic patients with nephropathy at Ahmadu Bello University Teaching Hospital, ABUTH, Zaria, Nigeria. Retrospective and cross-sectional research designs were used to collect data on drug use indicators from the prescriptions of patients who met the eligibility criteria. In addition, patient care indicators were assessed prospectively while patients were being attended to by physicians and pharmacists, respectively. Data were collected from 600 prescriptions over a period of 29 days and the results were presented using descriptive statistics. An average of 1.3 antidiabetic drugs per prescription was observed. Most of the drugs (88.6 %) were prescribed using generic names, 42.3 % and 62.3 % accounted for encounters with antibiotics and injections, respectively. Insulin (16.96 DDD/1000 diabetic patients with renal impairment) was 1.8 times more utilized than oral hypoglycaemic agents (OHAs). Among the OHAs, metformin (5.14 DDD/1000) was the most utilized, followed by glimepiride (2.76 DDD/1000), glibenclamide (1.04 DDD/1000), pioglitazone (0.37 DDD/1000) and gliclazide (0.09 DDD/1000). The average cost of a prescription in the facility was N13,423:94. In conclusion, it was observed that insulin was the most utilized antidiabetic agent among the population of patients in the facility and the cost of a prescription is high. Therefore, interventions to curtail the cost of the drugs, Social Health Insurance Programme should be adopted in the facility as most of the patients were not employed. Keywords: ABUTH, antidiabetic, drug utilization, drug use indicators, metformin, prescriptions Introduction Globally, diabetes is considered a progressive disorder and the leading cause of diabetic nephropathy which occurs in 20 – 40% of patients with diabetes and it is the single leading cause of end-stage renal disease (ESRD) (American Diabetes Association, 2013; WHO, 1999). In addition, people with type 2 diabetes and diabetic nephropathy are at increased risk for developing many other diabetic complications (Deshpande et al., 2008). The diabetes statistics of the International Diabetic Federation (IDF) showed that Nigeria has the highest number of people living with diabetes in Africa with an estimated 2,819,100 cases in 2010 which is projected to be 6,630,300 in the year 2045 (International Diabetes Federation, 2019). Since diabetes is considered the major cause of nephropathy in diabetic patients, this may suggest that Nigeria has the highest number of diabetic patients with nephropathy on the continent. S. Aliyu et al., ISSN: 2814-1423 56 Metformin is the drug of first choice for type 2 diabetics even in cases with renal impairments as contained in most good practice recommendations (Bonnet et al., 2011). Metformin, compared with other antidiabetic agents, is considered the drug that has been shown to reduce all-cause and cardiovascular mortality in patients with DM as reported in the UK Prospective Diabetic Study (UKPDS) (American Diabetes Association, 1998). However, renal tubular secretion is the major route of elimination of metformin. Therefore, any compromise in renal function may increase the risk for the development of Metformin Associated Lactic Acidosis (MALA) and other side effects (Setter et al., 2003). It has been reported that metformin-induced lactic acidosis carries a mortality rate of up to 50% (Nawaz et al., 1998) even with prompt treatment. Therefore, this study sought to assess the antidiabetic utilization among diabetic patients with nephropathy in Ahmadu Bello University Teaching Hospital, Zaria, Nigeria as there is a paucity of studies on the subject in this facility. This is necessary as understanding drug utilization patterns can provide valuable insights into current clinical practices, promote evidence-based decision-making, enhance patient safety, and guide the development of therapeutic protocols tailored for this specific population. Methods Ethical Approval Ethical approval for the research was obtained from the Health Research Ethics Committee of Ahmadu Bello University Teaching Hospital (ABUTHZ/HREC/X08/2016) and the National Health Research Ethics Committee (NHREC/10/12/2015) before the commencement of this study. Study Setting and Population The study site was Ahmadu Bello University Teaching Hospital Shika, Zaria, Kaduna State. The study was carried out among diabetes patients with nephropathy attending the diabetes clinic of the hospital. Research Design Both retrospective and prospective crosssectional research designs were employed for this research. Eligibility Criteria Only prescriptions of diabetic patients with renal impairment who had at least one antidiabetic medication prescribed and diabetic patients with an established diagnosis of nephropathy who reached the age of at least 18 years and who were receiving care for at least 3 months in the facility were included in this study. However, inpatients, newly diagnosed patients, patients less than 18 years old and those who declined to participate in the study were excluded. Data Collection A descriptive retrospective study was used to assess data on prescribing and complementary indicators from case folders that met the eligibility criteria of this study. Data were collected on a sample of 600 patients’ folders of diabetic patients with nephropathy as recommended by the WHO (1993) guideline for drug utilization. In addition, a prospective study was also undertaken on a purposive sample of 250 diabetic patients with nephropathy to determine the patients’ care indicators S. Aliyu et al., ISSN: 2814-1423 57 (average consulting and dispensing time, percentage of drugs dispensed, and adequate knowledge of correct dosage). Patient’s prescription plans were copied out in pre-designed data collection forms adapted from WHO guidelines on how to investigate drug use in health facilities. The data obtained were sorted and classified according to the WHO ATC/DDD (Anatomical Therapeutic Chemical/ Defined Daily Dose) Classification System (WHO, 1993). Costs/DDD were calculated in Naira using the hospital price list. Data were collected between January 2015 and May 2017. All the calculations were done according to the WHO (1993) guidelines for investigating drug use in health facilities as illustrated in the following equations. Drug utilization 90% (DU90%) was calculated by ranking (in descending order) the drugs by the value of defined daily doses (DDD) and determining how many drugs accounted for the 90% segment. The results were presented descriptively Prescribing indicators: 1. average number of antidiabetic drugs per encounter = total number of different antidiabetic drugs prescribed number of encounters surveyed 2. percentage of antidiabetics prescribed by generic name = number of antidiabetics prescribed by generic name total number of drugs prescribed ×100% 3. percentage of encounters with an antibiotic prescribed = number of antibiotics prescribed total number of drugs prescribed × 100% 4. percentage of encounters with an injection prescribed = number of patients encountered with injection total number of encounters surveyed × 100 5. percentage of drugs prescribed from the essential drug list = number of products prescribed from the essential drug list of the hospital total number of drugs prescribed ×100 Patient care indicators: 1. average consultation time = total time for a series of consultations actual number of consultations 2. average dispensing time = total time for dispensing drugs to a series of patients number of encounters 3. percentage of drugs actually dispensed = number of drugs actually dispensed total number of drugs prescribed × 100% S. Aliyu et al., ISSN: 2814-1423 58 4. percentage of patients′knowledge of correct dosage = number of patients who can adequately report the dosage schedule for all drugs total number of patients interviewed ×100% Facility indicators: 1. The availability of a copy of EDL: By stating yes (or) no. 2. availability of key drugs = number of specified products actually in stock total number of drugs on the checklist × 100% Complementary indicators: 1. average drug cost per encounter = total cost of all drugs prescribed number of encounters surveyed 2. percentage of drug costs spent on injection = cost of injections prescribed total drug cost × 100 The formulas for other parameters are shown below: a. DDD/1000/day: The DDD/1000/day was calculated as follows, Total amount of drugs used during study period(mg, units)×1000 DDD (mg, units) × Duration under review × total sample size b. Cost Per DDD: The Cost Per DDD was calculated as follows, Cost of one tablet or vial of insulin (N)×DDD(mg, units) Strength of one tablet or vial of insulin(mg, unit) Results A total of 600 case folders of diabetic patients with renal impairment between the months of January 2015 and May 2017 inclusive were reviewed. It was found that 247 (41%) and 353 (59%) were male and female respectively. An average number of all drug classes of 3.9 and 1.4 of antidiabetics were found per prescription. Most of the drugs were prescribed using generic names (88.6%). There a high rate of antibiotics (42.3%) prescriptions among the sample of prescriptions assessed, injections accounted for (62.3%) of the total number of drugs, and 97.91% of all the drugs were prescribed from the Nigerian National Essential Drug List except pioglitazone. The average consultation and dispensing time were 13 and 5 minutes respectively. Most of the drugs (89%) were dispensed to the patients and the majority of the patients (91%) had adequate knowledge of the correct doses of their medications. There was the availability of essential drug lists and hospital formulary in this facility, and all the key antidiabetics were available in the pharmacy. The average cost of filling antidiabetic prescriptions was N1,762:86 (US$4.31), and 92% of the cost of the drugs was spent on injections (Table 1). Finally, the DU90% indicates that insulins and metformin account for the most S. Aliyu et al., ISSN: 2814-1423 59 utilized antidiabetic agents in the facility while the beyond DU90% segment accounts for the drugs that were used either as an alternative option or in combination with other drugs (Table 2). Table 1: Drug Use Indicators among Patients with Diabetic Nephropathy in ABUTH During the Period under Review Core Indicators Value WHO/INRUD Ideal Value Prescribing Indicators Average number of antidiabetics prescribed (n) 1.4 1.6-1.8 Average number of drugs prescribed (n) 3.9 1.6-1.8 Generics (%) 88.6 100 Antibiotics (%) 42.3 20-26.8 Injections (%) 62.3 13.4-24.1 National Essential Drug List (%) 97.91 100 Patient Care Indicators Average consulting time (min) 13 >10 Average dispensing time (min) 5 >1.5 Drugs dispensed (%) 89 100 Adequate knowledge of correct dosage (%) 91 100 Facility Indicators Availability of Essential drug list Yes Yes Key drugs available (%) 100 100 Complementary Indicators Average cost of antidiabetics per prescription (N) 1,763:86 - Percentage Cost of injection 92 - WHO/INRUD means World Health Organization/International Network for Rational Use of Drugs; n, number; %, per cent; min, minute S. Aliyu et al., ISSN: 2814-1423 60 Table 2: Antidiabetic Drug Utilization Pattern among Diabetic Patients with Nephropathy in the Facility During the Period under Review ATC code Drug prescribed Percentage DDD/1000 inhabitants/day Cost/DDD (N) A10AB Fast acting insulin 30.86 19.67 110:00 A10BA02 Metformin 28.78 1.10 57:20 A10AC Intermediate acting insulin 24.28 15.47 154:88 Within DU90% segment 83.92 36.24 322:08 A10BB12 Glimepiride 7.72 0.20 101:63 A10BB01 Glibenclamide 5.79 0.07 23:22 A10BG03 Pioglitazone 2.09 0.05 39:50 A10BB09 Gliclazide 0.48 0.01 75:60 Beyond DU90% segment 16.08 0.33 239:95 Total = within DU90% + beyond DU90% 100.00 36.57 562:03 ATC, Anatomical and Therapeutic Classification; DDD, Defined Daily Dose; n, number of prescriptions; DU90%, 90 percent drug utilization Discussion The high average number of drugs per prescription observed in this study was not surprising as diabetic patients with comorbidities may require multiple medications to achieve the desired treatment goal (Eze and Odunayo, 2010; Patel et al., 2013). Based on our search, there is no evidence in the literature on the assessment of drug utilization among diabetic nephropathic patients in Nigeria. However, a study on diabetic patients by Adibe et al. (2009) reported an average of 2.6 in their study in southeast Nigeria. In contrast, Ogbonna and Ezenduka (2014) reported a higher value of 4 in Nnamdi Azikiwe University Teaching Hospital at Nnewi, Anambra State, southeast Nigeria. Eze and Odunayo, (2010) reported an average of 4.7 in Olabisi Onabanjo University Teaching Hospital, Ogun State, southwest Nigeria. Also, Odusanya, (2000) reported an average of 3.5 in Lagos University Teaching Hospital. Furthermore, Chedi, et al., (2015) reported a higher value in Northern Nigeria. An average number of drugs in a prescription is a measure of polypharmacy (Vaniya et al., 2016) which is associated with increased incidence of drug-drug interaction, therapeutic error, contraindication, and adverse drug reactions (Bashrahil, 2010; Tamuno and Fadare, 2012). Furthermore, polypharmacy in a prescription and its associated clinical consequences may eventually lead to medication non-adherence, a decrease in treatment outcomes, and an increased overall cost of care (Upadhyay et al., 2007; Ghimire et al., 2009). It is preferable to keep the number of drugs per prescription as low as possible, to reduce S. Aliyu et al., ISSN: 2814-1423 61 the risk of such consequences (Vaniya et al., 2016). Polypharmacy can further be minimized by adhering to the standard treatment guidelines when prescribing (Chareonkul et al., 2002), educational interventions to the prescribers (Sipcic et al., 2007), and the use of a fixed-dose combination to reduce pill burden (Blix, 2016; Eze and Odunayo, 2010). The percentage of drugs prescribed by generic name accounted for 88.6%, slightly below the 100% recommended by the WHO/INRUD. Deviation from the recommended value is an indication that prescribers dwelled on branded products. This was obvious in the facility during the study period where it was observed that the prescribers had a high preference for a particular brand of metformin sustainedrelease formulation. The value observed for generic prescriptions in the facility was satisfactory and better than the findings of other studies in Nigeria. For example, Eze and Odunayo (2010), Adibe and colleagues, Babalola and colleagues, Ogbonna and Ezenduka (2014), Tamuno and Fadare (2012), and Ezenduka and colleagues reported 40.1, 72.5, 69.8, 58, 42.7 and 83% respectively for generic prescription in Nigeria. Furthermore, findings from other countries were as follows: Acharya and colleagues (2013) reported 4.3% in India, Desalegn (2013) reported 98.7% in Ethiopia, Akl and colleagues (2014) reported 95.4% in Egypt, Afriyie and Raymond (2014) reported 62.6% in Ghana. In some situations, generic prescribing is mandatory especially for drugs with narrow therapeutic windows (Lenjisa and Fereja, 2014). Furthermore, generic prescribing allows flexibility of stocking and dispensing various brands of a particular drug that are cheaper and as effective as proprietary brands (Eze and Odunayo, 2010). Similarly, generic prescription helps with improved communication and clarity among healthcare providers (Atif et al., 2016) and also reduces the possibility of prescription errors (Shankar et al., 2007). It also allows the pharmacist to maintain a more economic stock control system based on a smaller range of reasonably priced drugs (Chedi et al., 2015). The possible reasons for a low generic prescription from the literature include lucrative advertisements by the pharmaceutical sales representatives, insufficient availability of a generic drug in pharmacy (Ashar et al., 2016), clinical experience of prescribers with a particular brand, and lack the same confidence in generic drugs (Vaniya et al., 2016) and prescribers’ belief that the brand names are easier to remember as well as the frequent use of brand names during their training (Chedi et al., 2015). Similarly, the percentage of encounters with antibiotics in this facility was also above the WHO/INRUD cut-off value. This is not surprising as diabetic patients are prone to infections in comparison to the general population as demonstrated by one of the largest systemic reviews and meta-analyses of observational studies on the association between diabetes mellitus and incidents of infections (Abu-ashour et al., 2017). The high risk of infection in diabetic patients has been attributed to the reduced response of T cells, neutrophil function, and disorders of humoral immunity (Casqueiro et al., 2012). Further to this, diabetic foot ulcer is one of the common complication of diabetes mellitus which is usually polymicrobial caused by an array of microorganisms such as aerobic gram-positive cocci like Staphylococcus aureus, gram-negative S. Aliyu et al., ISSN: 2814-1423 62 bacilli (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa), and anaerobes (Saseedhara et al., 2017). In addition, Hamilton and colleagues (2013) reported in their study that patients with diabetes had doubled the incidence of hospitalization for infectious diseases vs that of matched non-diabetic controls. These may necessitate the use of antibiotics to curtail the scourge of infections in such patients. Afriyie and Raymond (2014) in Ghana, Assen and Abrha (2014) in Ethiopia had reported high use of antibiotics in their respective studies similar to the finding of this study. Studies have demonstrated that inappropriate use of antibiotics can lead to serious clinical problems, such as the emergence of drug resistance, superinfection, allergies, and other health hazards (Bashrahil, 2007). Inappropriate use of antibiotics may also necessitate the need to use more expensive antibiotics to treat common and life-threatening infections which may increase the cost of filling a prescription and eventually affect treatment outcome due to non-adherence. This study suggested that the WHO/INRUD cut-off value for antibiotics should be reviewed upward since it is known that population of diabetic patients are more prone to infections compared with the general population. The percentage of encounters with injections of 62.3% observed in this study was higher than the recommended WHO/INRUD value of 13.4 – 24.1% and was also higher when compared with various studies on drug utilization in the country. This was also consistent with the findings of Babalola and coworkers in this country. In contrast, Eze and Odunayo, (2010), Adibe et al. (2009) , Tamuno and Fadare, (2012) and Odusanya, (2000) reported 2.1, 7.9, 4.0 and 13.8% respectively. The values reported by these authors were even lower than the WHO ideal values for drug utilization. The high usage of injection observed in the facility could be attributed to the frequent use of parenteral antibiotics for the treatment of infections as well as insulin injection which was the most utilized antidiabetic drug among the population of patients in the facility which accounted for 55.14% for both fast and intermediate-acting insulin. All the prescriptions in the facility were in line with the national essential drug lists. Key drugs and essential drug lists were also available in the facility as recommended by WHO/INRUD norms. Adibe and co-workers, Tamuno and Fadare, (2012), and Sau and co-workers in their respective study, reported a similar trend with the findings of our study. The WHO advocates that all prescriptions should be done according to the national essential drug list developed from the WHO essential drug list model which is being reviewed every two years since its inception in 1977. Compliance with the national essential drug list and availability of key drugs in the facility may reflect rational prescribing to such population of patients. According to the WHO essential drug policy, essential drugs serve the priority healthcare needs of the majority of patients at low cost to both the government and patients. Furthermore, the availability of key drugs in generic form depicts that there is the accessibility of drugs in the facility as suggested by WHO. It was further stated that governments at all levels, the private sector and civil society each has vital roles and responsibilities in achieving universal access and affordability to essential drugs which have S. Aliyu et al., ISSN: 2814-1423 63 been considered as the fundamental human right (WHO, 2001). The average consultation and dispensing times observed in this study were within the WHO/INRUD cut-off values for rational use of drugs. An optimal consultation time is required for proper history-taking, complete physical examination, and appropriate health education instructions (Aslam et al., 2016). On the other hand, an optimal dispensing time allows pharmacists to offer adequate drug information to patients about the correct dosage, side effects they may experience, adverse drug effects, and counselling. which in turn may enhance compliance with treatment and lead to better treatment outcomes (Mudenda et al., 2016). The longer values for consultation and dispensing times observed in this study demonstrated that the facility had an adequate number of different healthcare personnel to cater to the healthcare needs of the patients. A study among the diabetic population in Nigeria by Adibe and coworkers has reported a similar trend with the findings of this study. The percentage of drugs actually dispensed and the patient’s knowledge about the correct dosage were slightly below the recommended value. The shortfalls in the percentage of drugs dispensed to the patients could be attributed partly to stockout (Ezenduka et al., 2014) and partly due to the financial status of the patients during clinic visits as well as patients’ preference to buy their drugs outside the hospital pharmacy. Patients’ knowledge of the correct dosage is essential for proper use of medication which may lead to better therapeutic outcomes. The high level of patients’ knowledge of the correct dosage observed in this study could be attributed to the higher consultation and dispensing times to the patients by the doctors and pharmacists respectively. Also, the dispensaries in the pharmacy department of the facility were fitted with counselling rooms where patients were being counselled on the proper use of their prescribed medication by the pharmacist in attendance. The average cost of antidiabetics in a prescription was very high in this facility. This is not surprising as most of the prescriptions contained insulin which contributed to the higher share of the cost. Further to this, the finding of this study also revealed that injections carried 92% of the total cost of prescriptions. The cost of drugs (N1,763:86 equivalent to US$4:31) observed in this study is high compared with the finding of a study in the southeastern part of the country where it has been reported N353 approximately US$2.4 as an average cost of a prescription (Adibe et al., 2009). However, the differences in cost may be attributed to exchange rates with time at the time for each study. By implication, the high cost of drug therapy may predispose patients to medication non-adherence and its devastating effects on the treatment outcomes. The study demonstrated that metformin is the most utilized oral antidiabetics in the facility even though the majority of the patients had a contraindication to its use. In support of this, evidence from retrospective studies has demonstrated that metformin is still in use even in cases of contraindications (Moores, 2009) due to its numerous benefits on treatment outcomes (Díaz et al., 2017). It is also an available, affordable, and well-tolerated drug. Similar to metformin, insulin is the most utilized injectable antidiabetic in the facility. It is being used alone or in combination with other drugs (particularly