Scientific Papers

Prescription pattern analysis of Type 2 Diabetes Mellitus: a cross-sectional study in Isfahan, Iran | BioData Mining

Second level of ATC

Although it is not accurate and straightforward to imply the exact prevalence of diabetes complications from the percentage of prescribed drugs, Table 4 may at least approximately suggest the prevalence order of the main diabetes complications. According to medical experts’ opinions, C10, C09, and B01, which are the top three associated medications, are mainly prescribed for treating Dyslipidemia, Hypertension, and Cardiovascular disease, respectively.

Third level of ATC

The results of ARM analysis of the third level of ATC (Table 5) showed that ARs with Right-Hand-Side (RHS) of ACE Inhibitors (C09A) or Angiotensin II Receptor Blockers (ARBs) (C09C) had significant values for the lift indicator. There is a clear recommendation in the Standards of Medical Care in Diabetes – 2021 [24] about the treatment of Hypertension in DM patients. Diabetic patients’ treatment of Hypertension should include drug classes that reduce Cardiovascular (CV) events in patients with diabetes. C09A or C09C are recommended as first-line therapy for Hypertension in individuals with diabetes and Coronary Artery Disease (CAD). Therefore, the mentioned co-prescription is aligned with diabetes treatment guidelines.

Fourth level of ATC

First, as shown in the results, there is a strong AR indicating the prescription of HMG CoA Reductase Inhibitors (C10AA) with Drugs Used in Diabetes. According to the Standards of Medical Care in Diabetes – 2021 [24], T2DM patients have an increased prevalence of Lipid Abnormalities, contributing to their high risk of Atherosclerotic Cardiovascular Disease (ASCVD). Statin therapy has proven effects on ASCVD consequences in subjects with and without Congenital Heart Disease (CHD). Statins are the drugs of choice for Low-Density Lipoprotein (LDL) Cholesterol-lowering and Cardioprotection for both primary and secondary prevention. Therefore, the above-mentioned AR suggests that physicians adhere to the treatment guidelines.

Second, according to our results, the prescription of Platelet Aggregation Inhibitors excl. Heparin (B01AC) is meaningfully associated with Drugs Used in Diabetes. In fact, it is proved that diabetic patients are more likely to develop Coronary and Peripheral Vascular diseases than non-diabetic subjects, and B01AC is known for the primary and secondary prevention of vascular events [18]. That is the reason why the prescription of B01AC is common in these patients. Therefore, our result is aligned with the diabetes treatment approach.

Third, the results of the ARM analysis of the fourth level of ATC showed that the prescription of Organic Nitrates (C01DA) is highly associated with Drugs Used in Diabetes. Since diabetes-associated vascular dysfunction, as well as Nitrate Tolerance, adequately responds to antioxidant therapy, this may indicate the efficacy of prescribing Organic Nitrates in diabetic patients [25].

Fifth level of ATC

First, among Angiotensin II Receptor Blockers (ARBs), Plain (C09C) drugs, Losartan (C09CA01) as an RHS had the most significant lift. Although the main effects of Losartan are due to its ATC class and are the same as those of other approved ARBs, it also has some unique benefits. For instance, a shorter duration of action, uricosuric effect, attenuation of platelet aggregation, and protective effect on the kidney [26]. Our results suggest that physicians preferred prescribing an ARB with some effects on other diabetes complications.

Second, Hydrochlorothiazide (C03AA03) and Furosemide (C03CA01) are not commonly prescribed for controlling high blood pressure. However, the results show strong lift values for these drugs. It is mainly due to their Renoprotective [27] and Cardioprotective [28] effects, which are needed to treat common diabetes complications such as Renal Insufficiency and Heart Failure.

Third, the extracted ARs of the fifth level of ATC indicate that Thiamine (vit B1) (A11DA01) is more likely to be prescribed to diabetic than non-diabetic patients. The clinical effectiveness of Thiamine (vit B1) in controlling diabetic complications has been investigated in several studies [29, 30]. According to their results, this vitamin has an effective role in Diabetic Endothelial Vascular Diseases, Lipid Profile, Nephropathy, Cardiopathy, Retinopathy, and Neuropathy.

Fourth, the findings of co-prescription patterns in the fifth level of ATC have evidenced the strong bond between Gabapentin (N03AX12) and Drugs used in diabetes. Although Gabapentin is primarily used as an anti-epileptic agent, there is an increasing pattern of its utilization as an initial pharmacologic treatment in diabetic neuropathy [31]. The added value of the hierarchical analysis of co-prescription patterns performed in this study was finding such strong rules hidden throughout previous steps.

Fifth, another interesting finding is that Thiamine (vit B1) and Gabapentin are usually associated with the prescription of Insulin which is a sign of more advanced stages of diabetes.

Age- and gender-wise findings

The most noticeable difference found in the gender-wise analysis was the higher lift value of Thyroid Preparations in females compared to males. Although this finding is sporadically mentioned in the literature, the necessity of thyroid function screening is not well established in the clinical guideline of diabetes management [24, 32, 33].

Furthermore, our results revealed that Acetylsalicylic Acid (Aspirin) was found to be associated with some of the Drugs Used in Diabetes in the young age category of males, whereas this association was not observed in young females. This gender difference was also evident in the middle-aged group, where the number of extracted ARs for females was almost half that of males, and the average support, confidence, and lift for middle-aged males were higher than those for females. However, in the old age category, the number of rules for females increased and even slightly exceeded that for males, and we observed slight differences in quality measurements of the mentioned AR for males and females. This may suggest that the gender differences in the association between Aspirin and Drugs Used in Diabetes become less pronounced as individuals age.

In age-wise analysis, the results revealed that as one gets older, Vit B1 appears in the top rules, which may be an indication of neuropathy onset.

Overall findings and possible implications

Through data mining, we revealed the current pattern of diabetes management in a developing country, and showed that the care provided in Iran is relatively evidence-based and physicians mostly adhere to guidelines. This is an important finding, as it suggests that the healthcare system in Iran is providing appropriate diabetes care despite limited resources. Additionally, we identified the order of most frequent comorbidities associated with diabetes, which can inform care by providing healthcare decision-makers and strategists with valuable insights to prioritize their efforts and resources towards the most prevalent comorbidities. This may lead to more effective management of diabetes. Furthermore, based on our findings, we would like to suggest that diabetes guidelines consider including thyroid function screening, particularly for females with diabetes. It seems to be crucial for physicians to consider lab tests of thyroid disorders in this population, as this could have significant implications for preventive care and diabetes management.

Strengths and limitations

The results are based on data from the total rather than a sample of insured patients in Isfahan city; therefore, the risk of selection bias is low. To the best of our knowledge, previous similar studies were conducted with roughly a thousand samples [34,35,36,37,38,39]. In this study, we examined the prescriptions of 91,505 diabetic patients, which is way beyond the sample size of other research projects in this discipline. Additionally, the mentioned studies only found the prescription patterns regarding one level of ATC. However, we drilled down into all ATC levels for a comprehensive analysis.

Since our database is comprised of claims data, all patients were insured, and the results might not apply to the general population. In addition, some insured patients would have preferred to purchase their medications over-the-counter (OTC), and therefore no medical prescription was captured for them. Moreover, the lack of ICD-Code was one of the main limitations of this study, and this challenge was met by implementing a rule framework based on medical experts’ opinions.

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