Utilization Pattern of Anti-Diabetic Drugs in Type 2 Diabetes Mellitus in Tertiary Care Hospital.

 

Ms. Merry Raphael¹, Dr. Vijayanarayana K², Dr. GirishThunga³, Dr. Karthik Rao N⁴,

Dr. Sreedharan N²

¹Student, Department of Pharmacy Practice, Manipal College of  Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

²Associate Professor, Department of Pharmacy Practice, Manipal College of  Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

³Assistant Professor, Department of  Pharmacy Practice, Manipal College of  Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

⁴Assistant Professor, Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

 

ABSTRACT:

Background: Diabetes mellitus is a major public-health related problem. The increase in prevalence rates has led to an increase in the economic burden, worldwide. To manage the disease in a better way, Drug utilization research can be used as a strategy to justify the drug therapy.

Aims: To study the drug prescribing pattern of anti-diabetic drugs in newly diagnosed type 2 DM patients.

Materials and methods: A retrospective observational study was carried out in a tertiary care hospital. As per the study criteria, data was collected from medical records department (MRD) registry using ICD code E 11.9.Data was analysed using SPSS 20.0 and the DDD per 100 bed-days was calculated.

Results: A total of 662 patients were newly diagnosed with type 2 DM. The mean age of study population was 52.5 ± 12.5 years and 427(64.5%) patients were male. Hypertension was the most common comorbidity observed in 189 (28.5%) patients. Among the anti-diabetic drugs, the utilization of insulin (0.088 DDDs per 100 bed-days in 2013 and 0.16 DDDs per 100 bed-days in 2014) was highest and among the oral anti-diabetic drugs the utilization pattern of metformin (0.058 DDDs per 100 bed-days  in 2013 and 0.071 DDDs per 100 bed-days in 2014)  was the highest in both 2013 and 2014.

Conclusion: Biguanides (metformin) was highly prescribed anti-diabetic drug in both single and combination drug therapies. This study shows that the treatment pattern of type 2 DM patients is in accordance to the NICE (National Institute for Health and Clinical Excellence) guidelines.

 

 

 

 

INTRODUCTION:

The Drug Utilization (DU) study mainly emerged in the mid-1960s in United Kingdom and Northern Europe.^1,2

 

 “WHO defined the drug utilization research as the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences”^3,4,5 In 1996, WHO developed the Anatomical Therapeutic Chemical Classification / Defined Daily Dose (ATC/DDD) system. This system was used to enhance and ease the drug utility which was later evolved as a statistical method for presenting the DU statistics.^3,6 Through this DU study in our hospital, physicians can be provided with feedbacks that can be assisted in the design of educational programs which may in turn help in the improvement of prescription and drug usage. Patients compliant to the treatment can be assessed through DU Studies. The quality of patient’s care can be improved by participating in DU study programs. This can be achieved by preventing the adverse drug reactions and the irrational or unnecessary utility of drug therapy. In the current global scenario the prevalence of diabetes is high and it is predicted to raise further in the upcoming years.^7,8Study on the newly diagnosed Type 2 DM patients will help in the optimal management of patient therapy at the time of diagnosis so that disease related complications can be prevented. ^{9, 10, 11}The aim is to study the drug prescribing pattern of anti-diabetic drugs in newly diagnosed type 2 DM patients.

 

MATERIALS AND METHODS:

A retrospective observational study was conducted in a tertiary care teaching hospital of South India. Ethical approval was obtained from the Institutional Ethics Committee of the hospital. Data was collected from medical record section by International Classification of Diseases (ICD) which codes for Non-Insulin Dependent Diabetes Mellitus - E 11.9 (without Complications) from 2013 to 2014 in a suitable designed case record form. All the patient related data includes demographics, complaints on admission, history of patient diagnosis, treatment and progress chart and the discharge summary. Data was entered in SPSS 20.0 and analysed for the results. As our study is based on drug utilization pattern for in-patients, the formulae of DDD/100 bed‑days is used.

 

                      Drug Consumption during the study period (mg)X 100

DDD/100bed-days =-----------------------------------------------------------

                 WHO DDD(mg) X period of study X bed strength X                                                                               average occupancy index

 

·         Period of study is 365 days for both the years 2013 and 2014

·         Bed strength was 2032 for both the years

·         Average occupancy index is 0.69 for 2013 and 0.68 for 2014. This was calculated by dividing the number of beds occupied by total number of beds in the hospital.

 

RESULTS:

The total type 2 DM patients admitted in our hospital in the year 2013 and 2014 were 8400. Among these 302 (8.3%) patients were newly diagnosed in 2013 and 360 (7.5%) patients in 2014 which added to 662 (7.88%) patients. The demographic characteristics of the patients are given in the Table 1. The mean age of our study population was found to be 52.5 ± 12.5 years. A high proportion of the study population were males who constituted 64.5 %. Amongst the social habits, majority were smokers (8.8 %). The mean Body Mass Index (BMI) of the study population was found to be 24.7 ± 4.7 kg/m². Among which 164 (31.96%) patients were overweight and 67 (13.07%) were obese. BMI data for 149 patients was not recorded as they were bedridden. In our study it was found that 5 (0.8%) patients had a family history of diabetes. Mean hospitalization days was found to be 6.9 ± 4.2 days and the median was 6(4) days.

 

In our study it was observed that 468 (70.69%) patients had comorbidities, out of which, 189 (28.5%) patients had hypertension followed by 146 (22.05%) patients with respiratory related comorbidities (eg: bronchial asthma, COPD, pneumonia).

 

Table 1: Demographics of the patients

Patient Demographics (n= 662 )
Male, n (%)	427 (64.50 %)
Female, n (%)	235 (35.50 %)
Mean age ± SD in years	52.50 ± 12.51
Smoker, n (%)	58 (8.8%)
Alcoholic, n (%)	35 (5.3%)
Tobacco chewers, n (%)	6 (0.9%)
Mean BMI± SD in kg/m2	24.71 ± 4.76
under weight, n(%)	51 (9.95%)
normal     , n(%)	231 (45.02%)
overweight, n(%)	164 (31.96%)
obese, n( %)	67 (13.07%)
Family History of Diabetes, n(%)	5 (0.8%)
Mean Hospitalization Days± SD	6.86 ± 4.18
Comorbidities, n(%) 468 (70.69%)
1.       Hypertension	189 (28.5%)
2.       Respiratory	146 (22.05%)
3.       Infectious	85 (12.83%)
3.1 Urinary tract infection	41 (6.2%)
3.2 Dengue	25 (3.8%)
3.3 Abscess	19 (2.9%)
4.       Ischemic heart disease	28 (4.2%)
5.       Dyslipidaemia	20 (3%)

 

Among the study population 89 (13.4%) patients had generalised weakness followed by 70 (10.6%) patients with fatigue and 41 (6.2%) patients with polyuria. Apart from these, 198 (29.9%) patients had fever followed by 134 (20.2%) patients with cough as shown in Table 2.

 

Table 2: Clinical characteristics of the patients

Clinical characteristics	n (%)
1 Diabetic Specific
Generalised weakness	89 (13.4%)
Fatigue	70 (10.6%)
Polyuria	41 (6.2%)
Burning micturition	31 (4.7%)
Polydipsia	22 (3.3%)
Polyphagia	18 (2.7%)
2 Others
Fever	198 (29.9%)
Cough	134 (20.2%)

 

In our study population, 261 (39.42%) patients received single anti-diabetic treatment and 194 (29.30%) patients received double anti-diabetic treatment and 118 (17.82%) patients received multiple anti-diabetic treatments which included more than two different drug treatments while 89 (13.44%) patients were on dietary modification

 

Oral anti-diabetic drugs were prescribed to 264 (39.9%) patients and 123 (18.6%) patients received only insulin therapy and 186 (28.1%) patients received a combination of oral anti-diabetic drugs and insulin therapy as shown in Table 3.

 

 

Table 3: Oral / Insulin Therapy of the patients:

Oral / Insulin Therapy	n (%)
Oral	264 (39.9%)
Insulin	123 (18.6%)
Oral and insulin combination	186 (28.1%)

 

Biguanides was received by385 (58.2%) patients followed by 309 (46.67%) patients received insulin as shown in Table 4.

 

 

Table 4: Treatment with anti-diabetic drugs of the patients

A combination of biguanides and insulin was received by 79 (11.9%) patients followed by 61 (9.2%) patients received a combination of sulfonylureas and biguanides as shown in Table 5.

 

Table 5: Combination of Anti-Diabetic Drugs of the patients

 

Utilization of anti-diabetics expressed as DDDs per 100 bed-days:

DDD was calculated separately for 2013 and 2014 in terms of DDDs per 100 bed-days. The DDD system is usedas a statistical method for presenting the DU statistics which allows measurement of drug consumption across different therapeutic groups.

 

As our study is based on the drug utilization pattern for in-patients, the formulae of DDD/100 bed‑days is used.

 

Among the anti-diabetic drugs, the utilization of Insulin was highest and among the oral anti-diabetic drugs the utilization pattern of metformin was the highest followed by glimepiride in both 2013 and 2014 as shown in Table 6.

 

 

 

Figure 1: Comparison of DDD/100 bed-days for 2013 and 2014

 

Table 6: The Defined Daily Dose (DDD) for the year 2013 and 2014

S.No.	Drugs Prescribed	ATC Code	WHO DDD	Total no. used in 2013	DDDs per 100 bed-days (2013)	Total no. used in 2014	DDDs per 100 bed-days (2014)
1.	Insulin	A10AD01	40 U	18093 U	0.088	33221U	0.16
2.	Metformin	A10BA02	2 g	598950 mg	0.058	716750 mg	0.071
3.	Glimepiride	A10BB12	2 mg	252 mg	0.024	210 mg	0.02
4.	Glibenclamide	A10BB01	10 mg	473.75 mg	0.009	402.75 mg	0.0079
5.	Glipizide	A10BB07	10 mg	310 mg	0.006	742.5 mg	0.014
6.	Pioglitazone	A10BG03	30 mg	30 mg	0.00019	262.5 mg	0.0017

 

 

We observed that the total anti-diabetic drug consumption in the medicine ward showed increased trend in 2014 than in 2013 (0.18 DDD/100 bed-days in 2013 and 0.27 DDD/100 bed-days).

 

The utilization pattern of insulin, metformin, glipizide and pioglitazone showed an increased trend in 2014 than in 2013, while a decreased trend in the utilization pattern was observed for glimepiride and glibenclamide as shown in Figure 1.

 

DISCUSSION:

Our study was a retrospective, observational study which was conducted on 662 patients who were newly diagnosed with type 2 DM. This study is focused on the drug prescribing patterns of anti-diabetic drugs in the newly diagnosed type 2 DM patients.

 

The mean age of the study population was found to be 52.5 ± 12.5 years which was higher compared to the study conducted in India by Shukla et al., on newly diagnosed DM patients, where the mean age was 48.4 ± 9.07 years.

 

While the mean BMI in our study was found to be 24.7 ± 4.7 kg/m², which similar to a same study by Shukla et al., with a BMI of 24.67 ± 4.41 kg/m².¹³

 

High proportions in this study were males with 427 (64.5%) patients. This is similar to the reports obtained in few Indian studies^12,14,15,16 and is in contrast to a study by M. S. Alam et al., where high proportions of the study population were females¹⁷. The male: female ratio was 1.8:1 in our study. A study conducted by Deepa et al., on newly diagnosed type 2 DM patients had a male: female ratio of 1.6:1, which was almost similar to our study.¹⁸

 

Dietary modification for diabetes was observed in 89 (13.44%) patients. A study conducted by Diabetes Prevention Program Research Group showed that the lifestyle intervention could delay or prevent the development of diabetic related complications¹⁹

 

Although lifestyle changes remain the cornerstone of diabetes management, individually they are often insufficient to enable patients to maintain normal blood glucose levels. Drug therapy, therefore, forms an integral component in the management of diabetes mellitus.^20,21

The mean of anti-diabetic drugs per prescription was found out to be 1.39 ± 0.89 drugs. A study conducted by Das et al on newly diagnosed type 2 DM patients revealed similar results with a mean number of drugs per prescription of 1.83±1.31 drugs.²²

 

The highest number of patients in our study received single anti-diabetic treatment with 261 (39.42%) patients. In a study conducted by Patel B et al., had similar results where 81.58% patients received single anti-diabetic treatment among all the therapies including single, double and multiple drug therapies.²³

 

Metformin alone 385 (58.2%) and combinations  (metformin and insulin 79 (11.9%) and a combination of sulfonylureas and metformin 61 (9.2%)) were found to be the most commonly prescribed oral anti-diabetic drug, which is similar to the findings of Johnson et al, 2006,²⁴Palaian S et al, 2007,²⁵Sultana G et al, 2010;²⁶Yurgin N et al, 2007;²⁷ and in contrast to the studies by Al Khaja KA et al, 2001;²⁸ Chiang CW et al, 2006;²⁹ R Ramesh et al, 2011;¹⁵ where, sulfonylureas was found to be highly prescribed anti-diabetic drug.

 

This result is contradictory to the findings of other studies done in India³⁰ and Hong Kong³¹which revealed that the most commonly prescribed anti-diabetic drug was glibenclamide. While, a study by Sudha et al, 2008¹⁹ also reported, Metformin to be the most commonly prescribed drug.

 

DDD system is used as a tool which allows measurement of drug consumption across various therapeutic groups. DDD/100 bed‑days for hospital in-patients provide an estimate of drug consumptions. In this study the DDD was calculated separately for 2013 and 2014 in terms of DDD per 100 bed-days and the results were compared.

 

Among the anti-diabetic drugs the utilization of insulin was found to be the highest in terms of the DDD calculated (0.088 DDDs per 100 bed-days in 2013 and 0.16 DDDs per 100 bed-days in 2014). One possible reason of prescribing Insulin to newly diagnosed type 2 DM patients is that, if the HbA1C is above the target level, oral anti-diabetic drugs may fail to prevent the progression of the disease thereby making it necessary to initiate intensive insulin therapy over time. A study by Abdi, et al., also showed similar results where insulin was found to be the most highly utilized therapy (9.68 DDDs per 100 bed-days).

 

Biguanide (metformin) was found to be the highest utilized (0.058 DDDs per 100 bed-days in 2013 and 0.071 DDDs per 100 bed-days in 2014) followed by glimepiride (0.024 DDDs per 100 bed-days in 2013 and 0.02 DDDs per 100 bed-days in 2014). Similar study by Abdi, et al., showed that among the oral anti-diabetic drugs glimepiride (0.69  DDDs per 100 bed-days ) was found to be the highest utilized followed by (metformin 0.46 DDDs per 100 bed-days ).¹⁴

 

During the study period total anti-diabetic drug consumption in the medicine wards was (0.18 DDD/100 bed-days in 2013 and 0.27 DDD/100 bed-days), similar study by Abdi, et al., showed that the total anti-diabetic drug consumption in their medicine wards was 13.42 DDD/100 bed‑days.

 

Metformin was the most commonly prescribed drug in our study and this fact complies with guidelines as the preferred anti-diabetic agent and first line therapy for type 2 DM. These guidelines also suggest that at the time of diagnosis, metformin must be initiated along with lifestyle modifications. It has an added advantage of not provoking hypoglycaemia, improving lipid profile and it can be associated with any other anti-diabetic agents. ^{32, 33}

 

The main limitations of the study are that, since it was a retrospective observational study, correlation of drug therapy and the effect in reference to HbA1c values could not be done.  In this study, only two years data were collected. Data collected from one centre may not represent the type 2 DM population of the entire South India. Studies involving a larger population are required to compare the findings of this study. It might be possible that the prescription pattern for patients presenting on out-patients basis might differ in comparison to the in-patients.

 

CONCLUSION:

The prevalence of type 2 DM was more common in male patients 427 (64.50 %). The common symptoms specific to type 2 DM was found to be generalised weakness followed by fatigue and polyuria. Hypertension was the most common co-morbid condition. On the basis of DDD/100 bed-days, the utilization of insulin was highest among the anti-diabetic drugs. Among the oral anti-diabetic drugs the utilization pattern of metformin was the highest followed by glimepiride in both 2013 and 2014.Metformin was the highly prescribed anti-diabetic drug in both single and combination drug therapies. This study shows that the treatment pattern followed is in accordance to the NICE (National Institute for Health and Clinical Excellence) guidelines.

 

LIST OF ABBREVIATIONS:

1.        ATC-Anatomical Therapeutic Chemical Classification

2.        BMI-Body Mass Index

3.        COPD- Chronic Obstructive Pulmonary Disease

4.        DDD-Defined Daily Dose

5.        DM-Diabetes Mellitus

6.        DU- Drug Utilization

7.        HbA1c- Glycosylated Haemoglobin

8.        ICD-International Classification Of Diseases

9.        IEC-Institutional Ethics Committee

10.     MRD-Medical Record Department

11.     NICE-National Institute For Health And Clinical Excellence

12.     SPSS-Statistical Package For Social Sciences

13.     WHO-World Health Organization

 

ACKNOWLEDGEMENT:

The authors would like to acknowledge Manipal University, Kasturba Hospital, Manipal, Manipal College of Pharmaceutical Sciences for providing the necessary facility to conduct the study.

 

CONFLICT OF INTEREST:

There is no conflict of interest among the authors.

 

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Accepted on 07.05.2017           © RJPT All right reserved