Prescribing Trends of Antidiabetic Fixed dose combinations in a rural tertiary care teaching hospital in Central India: An Observational, cross-sectional study

Diptendu Santra*, Sangita Totade

J.N. Medical College, Sawangi (M), Wardha (Maharashtra)

*Corresponding Author E-mail: diptendusantra@gmail.com

ABSTRACT:

Objective: To assess prescribing trends of Fixed dose combination antidiabetics in Diabetes Mellitus patients.

Materials and Methods: An observational, cross-sectional study was carried out in the Medicine OPD of AVBRH, Sawangi(M), Wardha. A total of 500 Diabetes Mellitus Patients were selected for the study after fulfilling the inclusion/exclusion criteria.

Results: Out of 500 patients 484 patients were of type-II DM in whom 5 FDCs were prescribed. Maximum prescribed FDCs were of Metformin and sulfonylurea Metformin + Glimepiride (n=74) and Metformin + Glipizide (n=37). Following FDCs were Metformin + Voglibose (n=52), Glimepiride + Pioglitazone (n=18) and least prescribed was Metformin+ Glimepiride + Voglibose (n=10). All the drugs were prescribed by brand names. Total of 191 patients (39.46%) were prescribed Antidiabetic FDCs.

Conclusion: All Antidiabetic FDCs prescribed were rational. FDCs in Antidiabetics are useful in combination therapy for increasing patient compliance and achieving euglycemia more effectively. .

KEYWORDS: Prescribing trends, Diabetes Mellitus, Fixed dose combinations

INTRODUCTION:

Diabetes has long emerged as a major health care problem in India. According to the Diabetes Atlas published by the International Diabetes Federation (IDF), there are an estimated 40 million persons with diabetes in India in 2007 and this number is predicted to rise to almost 70 million people by 2025 by which time every fifth diabetic subject in the world would be an Indian. Genetic predisposition combined with life style changes, associated with urbanization and globalization, contribute to this rapid rise of diabetes in India.¹

Various guidelines are available that are recommended for different classes of drugs to treat diabetes.²Drug utilization studies are powerful exploratory tools to ascertain the role of drugs in society.³These studies help in creating a sound socio-medical and health economic basis for healthcare decision making.⁴

Current guidelines for diabetes management by the International Diabetes Federation (IDF), American Diabetes Federation (ADA) and others tend to suggest initial monotherapy, along with lifestyle modification, followed by combination therapy only if monotherapy fails.^5,6Combination therapy is a routine practice in the management of T2DM. Drugs with complimentary mechanisms should be used to maximize the efficacy of combination therapy.⁶

The most commonly prescribed antidiabetic FDC in India, Metformin + Sulfonylurea targets both insulin resistance and deficiency. Metformin suppresses hepatic gluconeogenesis to reduce fasting glycemia, and also increases peripheral glucose uptake sulfonylureas increase insulin release from the β-cells, and work as long as same amount of β-cell residual function is present. This therapy has been shown to provide synergistic effect in many studies and meta- analysis.⁷

There is very less literature on prescription pattern of Antidiabetic agents in tertiary health facilities in this part of Central India. This observational, cross-sectional study is aimed at examining antidiabetic drug utilization in diabetic patients in a tertiary health facility in Wardha, Maharashtra.

MATERIALS AND METHODS:

The study was carried out at a tertiary care rural teaching hospital, Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha. This hospital is attached to Jawaharlal Nehru Medical College (JNMC), Sawangi (Meghe), Wardha, Maharashtra, India.

The patients were selected on a random basis after the inclusion and exclusion criteria were fulfilled. The study included only one prescription per patient during that particular hospital visit. Prior patient consent was taken. 500 prescriptions of Diabetes Mellitus patients fulfilling inclusion and exclusion criteria were analyzed in this study. Patients above 18 years with diabetes mellitus (with or without associated chronic complications/ co-morbidities) who gave informed consent were included in this study. Gestational diabetes mellitus and patients with acute complications like diabetic ketoacidosis, severe infection requiring higher antibiotics and patients with poor General Condition were excluded from the study.

The observations were presented in tables and figures wherever possible. The results are expressed as frequency, means and percentages at the relevant places. Chi square test was applied at relevant places and p value estimated. p value < 0.5 was considered to be significant for our study.

Results:

Out of the 500 patients, 16 patients were diagnosed to have Type-I DM and rest 484 with Type-II DM. Oral formulations and their Fixed dose Combinations were employed only in type II DM patients.

1. Age wise Distribution of type-II DM patients

The 484 type-II DM cases were divided into four age groups viz. ≤ 35 years, 36-45 years, 46-55 years and ≥ 55 years.

Mean age of the patients was 56.00 ± 11.48. Most patients were above the age of 55 and same (55.79%), followed by 46-55 years (26.03%) , 36-45 years (16.12%) and least patients below and equal age of 35 (2.07%). (Table No. 1; Figure No. 1)

Table No. 1 Age wise distribution of type II DM patients (n=484)

Age Group	Frequency	Percentage
≤35	10	2.07%
36 – 45	78	16.12%
46 – 55	126	26.03%
>55	270	55.79%
Total	484	100.00%

Figure No. 1

2. Sex Distribution

Type II DM was predominantly seen more in males (62.19%) than in females (37.81%). (Table No. 2 and Fig.2)

Table No. 2 Gender wise distribution of type II DM Patients (n=484)

Gender	Frequency	Percentage
Male	301	62.19%
Female	183	37.81%
Total	484	100.00%

Figure No. 2

3. Prescribing Pattern of Fixed Dose Combinations

Out of 484 type-II DM patients, 358 patients were on combination therapy. In these 354 patients, 191 patients were prescribed Fixed dose combination Antidiabetic drugs.

The maximally used FDC of Metformin + Glimepiride in various dose variations was prescribed in 74 patients. Metformin + Voglibose was the second commonest prescribed FDC, prescribed in 52 patients. Metformin + Glipizide(n=37), Glimepiride + Pioglitazone(n=18) were prescribed. A triple drug FDC, Metformin+ Glimepiride + Voglibose was prescribed in 10 patients, which was also the least prescribed FDC. (Table No.3 and Fig. No. 3)

Discussion:

The mean age in a study may be considered as a crude estimate of the age onset and presence of type 2 DM in patients of that particular setting. Mean age of patients in our study was 56.00 ± 11.48. This is in harmony with the general age prevalence of type 2 DM and the findings in majority of studies.. Studies in India by Agarwal et al⁸ and Ahmed QS et al⁹ (58.12±10.5 and 57.36±8.80 respectively) showed slightly higher values of mean age as compared to this present study.

Male preponderance (62.19%) was observed in our study. This could be due to gender bias in treatment seeking behavior and gender prevalence of the disease due to lifestyle choices.¹⁰Many studies show a male preponderance in their findings as evidenced from the studies in India by Agarwal et al⁸, Leelavathi DA¹¹, Kannan et al¹², Ahmed QS et al⁹ and Vengurlekar et al¹³; Mwanza PM¹⁴ from Nigeria and Boccuzzi et al¹⁵ from US showed high male gender proportion in their studies.

In our study, 191 patients (39.46%) were prescribed fixed dose combination antidiabetic drugs. Metformin + Glimepiride was the maximally prescribed FDC. Metformin + Glipizide was the second most commonly used FDC followed by Metformin+voglibose and Glimepiride+ Pioglitazone. A triple drug FDC, Metformin+ Glimepiride + Voglibose was also prescribed. All FDCs have constituent agents with differing mechanism of action and thus, these combinations fulfill one important criterion to be deemed as being rational.

Diabetic patients often suffer from co-morbidities and are elderly which brings compliance and medication adherence to play a major role in instituting ideal therapy. FDCs have a major advantage here by increasing compliance and also offer the advantage of better efficacy and side-effect profile.⁷

Dutta S et al¹⁶ reported a presence (36.93%) of FDC in their prescribing which is comparable to the findings of our study. Agarwal et al⁸ reported use of FDCs (20.25%), with FDC of glimepiride+Metformin to be the most commonly prescribed. Sivasankari et al¹⁷ also reported FDC of metformin and sulfonylureas to be employed the most.

Most popular antidiabetic FDCs in India constitute of metformin and second generation sulfonylureas. Both have different mechanism of action and many studies have reported that they help in achieving glycemic control better.^18,19

ConclusionS AND RECOMMENDATIONS:

Fixed dose combinations were prescribed to 191 patients. FDC of Metformin and Glimepiride was the most common amongst all prescribed FDCs and the prescribing behavior was rational and adhered to standard treatment guidelines. Combination therapy for diabetes is commonplace in current scenario. Antidiabetic FDCs like metformin+ glimepiride could be included in the list of available generic drugs. Central Drugs Standard Control Organisation should review the antidiabetic agents in National list of Essential Medicines, 2011 and update the same. It may include in addition to glibenclamide other second generation sulfonylureas like glimepiride which is used most in this category.

REFERENCES:

1. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013.

2. Definition, diagnosis and classification of diabetes mellitus: Report of WHO consultation. Publication W.H.O./ NCD/99.2) Geneva, Switzerland: World Health Organization; 1999

3. Introduction to drug utilization research / WHO International Working Group for Drug Statistics Methodology, WHO Collaborating Centre for Drug Statistics Methodology, WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services.p17.

4. Bakassas I, Lunde PK. National drug policies: The need for drug utilization studies. Trends Pharmacol Sci. 1986; 7:331–4.

5. IDF Clinical Guidelines Task Force. Global guideline for Type 2 diabetes. International Diabetes Federation. Brussels; 2005.

6. Kalra S, Gupta V. The diversity of diabetes. In Bajaj S, ed. ESI Manual of Clinical Endocrinology. Endocrine society of Indian,Hyderabad. 2010; 1-3.

7. Kalra S, Aggressive treatment in newly diagnosed diabetes with fixed dose combinations. Medicine Update. 2012; 12:247-53.

8. Agarwal AA, Jadhav PR, Deshmukh YA. Prescribing pattern and efficacy of anti-diabetic drugs in maintaining optimal glycemic levels in diabetic patients. J Basic Clin Pharma. 2014;5:79-83.

9. Ahmed QS, Sayedda K, Gupta D, Ansari NA. Prescribing agents of Antidiabetic Medications in a tertiary care teaching hospital, Bareilly, UP, India. JPSI. 2013; 2(1):41-46.

10. BeLue R, Okoror TA, Iwelunmor J, Taylor KD, Degboe AN, Agyemang C, et al. An overview of cardiovascular risk factor burden in sub-Saharan African countries: a socio-cultural perspective. Global Health 2009; 5: 10 http://dx.doi.org /10.1186/1744-8603-5-10 pmid: 19772644.

11. Leelavathi DA. Evaluation of Prescription Patterns and Cost of Illness of Type-2 Diabetic Patients in a Tertiary Health Care Hospital. [PhD thesis]. Manipal: Manipal University: 2012.

12. Kannan, Arshad, Senthil kumar. A study on drug utilization of oral hypoglycemic agents in type-2 diabetic patients. Asian J Pharm Clin Res. 2011; 4(4): 60-64.

13. Vengurlekar S, Shukla P, Patidar P, Bafna R, Jain S. Prescribing Pattern of Antidiabetic Drugs in Indore City Hospital. Indian J Pharm Sci. 2008; 70(5): 637–40.

14. Mwanza PM. Prescribing Patterns and Drug Cost Implications for Diabetic Patients in Eastern Province, Kenya [Msc Thesis]. Kenya; 2009[Internet] (cited 2014 May19). Available from: http://ir.jkuat.ac.ke/handle/123456789/1375.

15. Boccuzzi SJ, Wogen J, FoxJ, Sung JCY, Shah AB, Kim J. Utilization of Oral Hypoglycemic Agents in a Drug-Insured U.S. Population. Diabetes Care. 2001; 24(8):1411–1415.

16. Dutta S, Beg MA, Anjoom M, Varma A, Bawa S. Study of prescribing pattern in diabetes mellitus patients in a tertiary care teaching hospital at Dehradun, Uttarakhand. Int J Med Sci Public Health 2014;3(Online First). DOI: 10.5455/ijmsph.2014.130820141.

17. Sivasankari V, Manivannan E, Priyadarsini SP. Drug utilization pattern of anti-diabetic drugs in a rural area of tamilnadu, south india - a prospective, observational study. Int J Pharm Bio Sci. 2013 Jan; 4(1):514-19.

18. Gerich JE. Oral hypoglycemic agents. N Engl J Med. 1989; 321(18):1231-45.

19. Giugliano D, Quatraro A, Consoli G, Minei A, Ceriello A, De Rosa N, et al. Metformin for obese insulin-treated diabetic patients: improvement in glycemic control and reduction of metabolic risk factors. Eur J Clin Pharmacol. 1993; 44(2):107-12.).

Received on 01.01.2015 Modified on 08.01.2015

Res. J. Pharmacology & P’dynamics. 7(1): Jan.-Mar. 2015; Page 19-22

DOI: 10.5958/2321-5836.2015.00004.X

Drugs	Frequency
Metformin + Glimepiride	74
Metformin + Glipizide	37
Metformin + Voglibose	52
Metformin+ Glimepiride + Voglibose	10
Glimepiride + Pioglitazone	18
Total	191