DRUG UTILIZATION TRENDS OF ORAL ANTI-DIABETIC AGENTS AMONG DIABETES MELLITUS TYPE 2 PATIENTS IN A TERTIARY CARE HOSPITAL

DRUG UTILIZATION TRENDS OF ORAL ANTI-DIABETIC AGENTS AMONG DIABETES MELLITUS TYPE 2 PATIENTS IN A TERTIARY CARE HOSPITAL

Pushp Raj Gour, Kavita Dhar Bagati *, S Balakrishnan and Neha Bhasin

Department of Pharmacology, School of Medical Sciences and Research Sharda University Greater Noida, Uttar Pradesh, India.

ABSTRACT: Diabetes is a group of metabolic diseases and emerged as a major healthcare problem. According to the International Diabetes Federation (IDF), India has a large number of people suffering from diabetes, which will increase to almost 101 million by the year 2030. The pharmacotherapies of diabetes mellitus are diversified in their mechanism of action, safety profiles and tolerability. Drug utilization studies are important for the optimization of drug therapy. The present study aimed to evaluate the drug utilization pattern of anti-diabetic drugs in a tertiary care teaching hospital. It was a cross-sectional study, enrolled 255 patient’s prescriptions. Information was noted from prescriptions prescribed to the patients by a Doctor in prepared pro forma. It was found that combination therapy is predominant over monotherapy. The study has indicated metformin as the predominantly recommended oral anti-diabetic drug both as monotherapy and combination therapy. Metformin + glimepiride was the most commonly prescribed in combination therapy. The highest adverse drug reactions reported in our study are metformin + glimepiride which is different from other studies.

Keywords: Anti-diabetic agents, Drug utilization, Metformin, Adverse drug reactions

INTRODUCTION: Diabetes mellitus (DM) is a common metabolic disorder arising from a variety of pathogenic mechanisms, all resulting in elevated levels of blood glucose. It is a serious public health problem because of its complications ¹. According to International Diabetes Federation (IDF), India has a large number of people suffering from diabetes; 77 million adults in India suffered from diabetes in the year 2019 which is going to increase to almost 101 million by the year 2030 ². The oral hypoglycemic agents used in the pharmacotherapy of diabetes mellitus are diversified in their mechanism of action, safety profiles and tolerability ³. Selecting a suitable regimen rationally from groups of anti-diabetic agents is an important task for doctors ⁴.

Drug utilization studies are useful to know the current prescribing practices and also help to identify irrational prescribing. It is important to realize that the consequences of irrational prescribing can result in complications and also lowers cost-effectiveness. The present study was designed to evaluate the choice of drugs in type 2 diabetes patients in a tertiary care teaching hospital.

MATERIALS AND METHODS: It was a cross-sectional study conducted at AIIMS Bhopal. The Institutional Human Ethics Committee approved this study of AIIMS Bhopal with the reference number IHEC-LOP/2016/IM0085. The present study involved patients who were 18 years and above age with a diagnosis of diabetes type 2. The patients selected was interviewed, and the objectives of the study were discussed with them. Information was noted from prescriptions that had been prescribed to the patients by a Doctor in prepared pro forma. This pro forma included patient detail, anti-diabetic prescribed with its dose, frequency, duration and adverse drug reaction.

The data was recorded medication status of all patients was reviewed, organized and expressed as the counts and percentages.

RESULTS: The present study was conducted to assess the prescribing trends of drugs used in patients of diabetes mellitus type 2. During the study period, a total of two hundred and fifty-five (n = 255) patients were enrolled in the study. Out of 255 subjects 57.64 % (n = 147) were male, 42.35% (n = 108) were female and mean age of the sample was 53.9 (± 11.3) years. The study found a higher incidence of diabetes among the middle age group of 41-60 years Table 1.

TABLE 1:  DEMOGRAPHIC PROFILE OF PATIENTS

TABLE 2: UTILIZATION PATTERN OF ANTI-DIABETIC DRUGS

FIG. 1: ANTI-DIABETIC PRESCRIPTION PATTERN BASED ON THERAPY

The percentage of patients on anti-diabetic monot herapy 25.09 % (n = 64), dual therapy 54.90 % (n = 140), triple therapy 20 % (n = 51) in Fig. 1.

Mono Therapy: Out of 64 patients on monotherapy, the most commonly prescribed oral hypoglycemic agent was biguanides (metformin) 60 (23.52 %) followed by sulfonylureas (glimepiride) 4 (1.5 %) (Table 2).

Combination Therapy: out of the overall total 191 (74.9 %) patients on a combination therapy. Among the dual drug therapy, the study found that combination of metformin + glimepiride 70 (27.45%) was the most commonly prescribed regimen followed by metformin + sitagliptin 34 (13. 33%), metformin + vildagliptin 30 (11.76 %), metformin + glipizide 4 (1.5 %) and metformin + voglibose 2 (0.78 %). In present study 51 (20 %) patients were on triple drug therapy, out of which metformin + glimepiride + tenlegliptin 18 (7.05 %) most commonly prescribed followed by metformin + glimepiride + sitagliptin 14 (5.49 %), metformin + glimepiride + voglibose 10 (3.92 %), metformin + glimepiride + pioglitazone 9 (3.52%). M: Metformin, G: Glimepiride, S: Sitagliptin, V: Vildagliptin, GLZ: Glipizide, VOG: Voglibose,  T: Teneligliptin, P: Pioglitazone.

FIG. 2: PRESCRIPTION PATTERN OF ANTI-DIABETIC DRUGS

TABLE 3: ADVERSE DRUG REACTIONS OF ANTI-DIABETIC DRUGS

M: Metformin, G: Glimepiride, S: Sitagliptin, V: Vildagliptin, GLZ: Glipizide, VOG: Voglibose, T: Teneligliptin, P: Pioglitazone.

A total of 32 adverse drug reactions were identified in 32 (12.54 %) patients among 255 patients details were given in Table 3: neuropathic pain was the most common ADR observed in thirteen patients.

DISCUSSION: Diabetes mellitus are a major non-communicable disease that is growing very fast. India has a huge population of type 2 diabetes mellitus patients requiring lifelong treatment. The principle aim of a drug utilization study is to assess and evaluate the prescribing attitude of a physician and helps to promote the rational use of drugs. Out of 255 subjects 57.64 % (n = 147) were male, 42.35% (n = 108) were female and mean age of the sample was 53.9 (± 11.3) years. The Study was found a higher incidence of diabetes among the middle age group of 41-60 years (53.33%) Table 1. Different results were obtained in a study conducted at Chennai, in which out of 354 patients, 180 (51%) were male and 174 (49%) were female and the most commonly affected age group was over the age of 60 were affected 137 (39%) of patients ⁵.

It was found that 25.09 % of patients were on monotherapy with oral hypoglycemic agents compared to 74.9 % on combination therapy Fig. 1. But a study done at Navi Mumbai on 220 diabetes patients reported 30 % of patients on monotherapy and 70 % on combination therapy ⁶. The most commonly prescribed anti-diabetic drug was metformin Table 2; a similar result has been documented in studies conducted by Alex et al., Dhar et al., and Singla et al. ^{7, 8, 9}.

Metformin belongs to the biguanides class of oral anti-diabetic drugs is an attractive choice for overweight sufferers because of its weight-neutral quality. Additionally, when used as monotherapy, it hardly ever ends with significant hypoglycemia by lowering extrahepatic gluconeogenesis without elevating insulin levels. As a result, metformin is extensively taken into consideration as a perfect first-line agent for the remedy of type 2 diabetes; moreover, the low cost of metformin making it accessible for the patients. Our study also supported the same conclusion ⁷. According to the International Diabetes Federation, metformin allows the body to use its insulin more effectively. The present study also complies that most of the guidelines around the world recognize metformin as first-line therapy ².

This study reported that the second most common drug prescribed was glimepiride as monotherapy. These results conform to other previous studies of Venkateswaramurthy et al and Abidi et al ^{10, 11}. Glimepiride is a potent drug, and it also possesses less hypoglycemia; these are the reason for being prescribed at the second position in the present study ¹². Oral drug therapy will achieve greater control on glycemic targets; however, the progressive nature of type 2 diabetes mellitus usually requires a combination of two or more oral agents in the longer term ¹⁰. Among this two-drug combination therapy, metformin + glimepiride (27.45 %) was the most commonly prescribed Table 2. In the studies by Alex et al. and Venkateswaramurthy et al. metformin + glimepiride was the most commonly prescribed two-drug combination ^{7, 10}. But Ashutosh et al. was found that the most commonly prescribed combination among two-drug combinations was metformin + vildagliptin (37 %) followed by metformin + glimepiride (34 %) ⁶.

However, the most prescribed three-drug combination was metformin + glimepiride + teneligliptin (7.05 %) (Table 2), which is the contrast with the study done by different Sharma et al. Gliptins are selectively inhibits the dipeptidyl peptidase - 4 (DPP- 4) enzyme, which enhances the action of glucagon-like peptide - 1 (GLP-1) and glucose-dependent insulin tropic (GIP) 13. DPP- 4 inhibitors work on incretin hormones that are emitted in reaction to meal intake. GLP- 1 and GIP are the two well-marked incretin hormones ⁴. Due to their superior efficacy, weight - neutrality, low risk of hypoglycemia and excellent tolerability, the DPP - 4 inhibitors have been recommended as a first-line or add-on therapy ¹⁴.

DPP - 4 inhibitors like sitagliptin, vildagliptin, and teneligliptin were prescribed in this study. Sitagliptin has minimal hypoglycemic events and reduced weight gain when compared to sulfonylurea as some studies have shown that sitagliptin is not associated with an increased risk of adverse cardiovascular outcomes ¹⁵. In this study, voglibose was the third most commonly prescribed anti-diabetic as a triple-drug regimen with metformin and glimepiride. Voglibose inhibits the alfa glucosidase enzyme and helps in the digestion of complex carbohydrates ⁴.

The present study reported that pioglitazone with metformin and glimepiride was prescribed in 3.52 % of patients. Table 2,  results did not concur with the study done by Venkateswaramurthy et al. Pioglitazone comes under thiazolidinediones that help in insulin sensitivity 10. The addition of thiazolidinediones to metformin in a 24 week randomized, double-blind and parallel-group study reported significantly improved glycemic control ¹⁶. But according to a meta-analysis, patients on pioglitazone have an increased risk of bladder cancer ¹⁷. Moreover, due to safety and tolerability, particularly weight gain and vascular complications frequently limit the application of thiazolidinediones. Because of this, pioglitazone was prescribed to very few patients. Several new drugs are available, like Glucagone peptides agonists and DPP-4 inhibitors, with positive benefits. Oral drug therapy will attain great control of glycemic targets within a short period when used accordingly ¹⁰. Adverse drug reactions reported in our study population are hypoglycemia, diarrhea, abdominal pain, dizziness, dyspepsia, nausea, and vomiting Table 3. The highest adverse drug reactions reported in our study with the metformin + glimepiride group are different from other studies ¹⁸.

CONCLUSION: In the present study, most of the patients were on combination therapy, and overall dual therapy was found to be prominent. The prescribing trend appears to be moving towards combination therapy.

Metformin was predominantly prescribed, followed by glimepiride both as monotherapy as well as combination therapy. Among combination therapy, metformin + glimepiride was the most commonly prescribed diarrhea was the most common ADR observed.

ACKNOWLEDGEMENT: The authors are thankful to the Department of Medicine of AIIMS Bhopal for providing all the facilities necessary to carry out this work.

CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest.

REFERENCES: 

1. Devi KL, Raleng I, Sailo Z and Valte V: Drug utilization among diabetes mellitus patients in a tertiary care hospital in North-East India. Indian J Pharm Pharmacol 2020; 7(3): 177-80.
2. IDF Diabetes Atlas. 9^th ed. International Diabetes Federation 2019. Available from: http//www.idf.org. [Last accessed on 2020 Jan 29].
3. Ahmed M, Baqtiyar S, Khanum R, Fatima K and Fatima A: Drug utilization pattern of anti - diabetic drugs in type II diabetes patients in a teaching and general Hospital. Indo Am J Pharm Res 2020; 10(4).
4. Sarkar S, Srivastava V, Roy A and Mohanty M: Prescribing pattern of anti-diabetic drugs amongst pre - obese diabetic patients in tertiary care hospital - an observational study. Diabetes Obes Int J 2019; 4(2): 000196.
5. Meena, Priyanka B, Thirunavukkarasu J and Srinivasan V: Evaluate the prescription pattern of anti-diabetic patients attending medicine out-patient department of a tertiary care hospital. World J Pharm Sci 2019; 7(9): 137-143.
6. Ashutosh K, Ipseeta RM and Sandeep R: Assessment of prescription pattern of anti-diabetic drugs in the outpatient department of a tertiary care hospital. Int J Clin Endocrinol Metab 2017; 3(1): 01-07.
7. Alex SA, Sreelekshmi BS, Simitha S, Jiji KN, Menon AS and Devi U: Drug drug utilization pattern of anti - diabetic drugs among diabetic outpatients in a tertiary care hospital. Asian J Pharm Clin Res 2015; 8(2):144-46.
8. Dhar K, Patnaik M, Chopra S and Singh R: Recent trend in prescribing pattern of metformin in the pharmacotherapy of diabetes mellitus type 2 patients. IJP 2013; 45: 49.
9. Singla R, Bindra J, Singla A, Gupta Y and Kalra S: Drug prescription patterns and cost analysis of diabetes therapy in India: Audit of an endocrine practice. Indian J Endocrinol Metab 2019; 23: 40-5.
10. Venkateswaramurthy N, Md. Shejeem S and Sambathkumar R: Prescribing pattern of anti-diabetic drugs in type -2 diabetes patients. Int J Pharm Sci Res 2016; 7(11): 4550-55.
11. Abidi A, Rizvi DA and Ahmad A: Pharmacoeconomic and drug utilization study of anti-diabetic therapy in a tertiary care teaching hospital of northern India. Asian J Pharm Clin Res 2016; 9(3): 371-75.
12. Tripathi KD: Insulin, oral anti-diabetic drugs and glucagon. In: essentials of medical pharmacology, 8th ed. jaypee brother’s medical publishers (P) Ltd. New Delhi 2019; 280-305.
13. Sharma S, Sharma P and Sharma M: Prescription pattern in patients with type 2 diabetes mellitus and hypertension: a prospective study. Int J Med Res 2018; 3(2): 67-69.
14. Gutch M, Joshi A, Kumar S, Agarwal A, Pahan RK and Razi SM: Gemigliptin: Newer promising gliptin for type 2 diabetes mellitus. Indian J Endo Metab 2017; 21: 898-902.
15. Kapoor N and Thomas N: Oral anti-diabetic agents: Recently available novel oral anti-diabetic agents in India: A clinical review. Curr Med Issues 2017; 15: 169-76.
16. Bailey CJ, Bagdonas A, Rubes J, Mcmorn SO and Donaldson J: Rosiglitazone -metformin fixed – dose combination compared with uptritrated metformin alone in type 2 diabetes mellitus: a 24 week multicentrer, randomized, double blind, parallel group study. Clin Ther 2005; 27(10): 1548-61.
17. Adil M, Khan RA, Ghosh P, Venkata SK, Kandhare AD and Sharma M: Pioglitazone and risk of bladder cancer in type 2 diabetes mellitus patients: A systematic literature review and meta-analysis of observational studies using real-world data. Clin Epid Glob Health 2018; 6(2): 61-68.
18. Adhikari A, Indu R, Bhowal T, Sur TK, Das AK and Chakraborty P: Evaluation of adverse effects due to anti-diabetic and cardiovascular drugs in a tertiary care hospital in kolkata, west bengal, India. Int J Pharm Sci Res 2016; 7(7): 3101-06.
    

    ---

    How to cite this article:

    Gour PR, Bagati KD, Balakrishnan S and Bhasin N: Drug utilization trends of oral antidiabetic agents among diabetes mellitus type 2 patients in a tertiary care hospital. Int J Pharm Sci & Res 2021; 12(11): 6072-76. doi: 10.13040/IJPSR.0975-8232.12(11).6072-76.

    ---

    All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.