|Year : 2015 | Volume
| Issue : 4 | Page : 221-227
Study of utilization pattern and patient compliance of oral anti-hyperglycemic drugs in a tertiary care teaching hospital in Eastern India
Kunal Sharma1, Soumya Santra1, Ayon Bhattacharya1, Divya Agrawal2, Sanjay Kumar1, Sudhanshu Sekhar Mishra1
1 Department of Pharmacology, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
2 Department of Anatomy, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
|Date of Submission||12-Jan-2015|
|Date of Decision||29-Jan-2015|
|Date of Acceptance||17-Oct-2015|
|Date of Web Publication||2-Dec-2015|
Department of Pharmacology, IMS and SUM Hospital, B. O. Ghatikia, Bhubaneswar - 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Background: Diabetes mellitus is a major chronic health problem globally, so the patterns of drug utilization study of oral anti-hyperglycemic drugs are of chief concern to promote rational drug use in diabetics and make available the valuable information for the healthcare providers. Objective: This study was performed to determine the drug utilization pattern of oral anti-hyperglycemic drugs in Type-2 diabetes mellitus (T2DM) patients in a tertiary care teaching hospital in Eastern India. Materials and Methods: A prospective, observational, and noncomparative study was carried for 12 weeks in T2DM patients on oral anti-hyperglycemic drugs for at least 1 week. Results: Total 230 patients were enrolled with mean age of 54.66 ± 13.24 years and duration of diabetes was 8.71 ± 7.78 years. Among these, 78 (33.91%) were in the age group 51–60 years, 132 (57.39%) had a diabetic history of <10 years, and 168 (73.04%) had associated hypertension. Mean number of drugs prescribed were 7.01 ± 2.73. Total numbers of patients receiving more than five drugs were 162 (70.43%). The biguanide (85.21%) was the most commonly prescribed oral anti-hyperglycemic drugs followed by sulfonylureas (58.26%). The 97 (75.78%) female patients were shown good compliance as compared with 72 (70.58%) males. Conclusion: Metformin (Biguanide) was the most commonly prescribed oral anti-hyperglycemic drugs for Type-2 diabetes. This study indicates the clinical monitoring of the patient's compliance to the prescribed drug for achieving good glycemic control is also recommended, along with other comprehensive management such as life style changes, dietary modification, treatment of complications, and co-morbidities related to diabetes.
Keywords: Anti-hyperglycemics, combination drugs, compliance, diabetes, metformin
|How to cite this article:|
Sharma K, Santra S, Bhattacharya A, Agrawal D, Kumar S, Mishra SS. Study of utilization pattern and patient compliance of oral anti-hyperglycemic drugs in a tertiary care teaching hospital in Eastern India. J Obes Metab Res 2015;2:221-7
|How to cite this URL:|
Sharma K, Santra S, Bhattacharya A, Agrawal D, Kumar S, Mishra SS. Study of utilization pattern and patient compliance of oral anti-hyperglycemic drugs in a tertiary care teaching hospital in Eastern India. J Obes Metab Res [serial online] 2015 [cited 2019 Jun 17];2:221-7. Available from: http://www.jomrjournal.org/text.asp?2015/2/4/221/170896
| Introduction|| |
Diabetes mellitus has emerged as one of the major global public health problem. The World Health Organization (WHO) estimated around 347 million people worldwide have diabetes at present. India alone accounts for 65 million diabetic population, the second highest in the World after China. The latter has 98 million and is projected that the number of diabetics globally will reach 582 million by 2035. The WHO also projected that diabetes will be the seventh leading cause of worldwide deaths in 2030. More than 80% of diabetes related deaths occurred in low- and middle-income countries.
Diabetes is defined as a state of chronic hyperglycemia, which increases the risk of microvascular complications, namely retinopathy, nephropathy, and neuropathy. However, diabetes is also associated with the increased risk of macrovascular complications including cardiovascular disease, cerebrovascular accident, peripheral vascular disease, and infarct, which are the leading causes of mortality in patients with diabetes., The key features of Type-2 diabetes mellitus (T2DM) are a defect in insulin resistance and/or insulin secretion, which lead to hyperglycemia, the interruption between normal relationship of insulin sensitivity and pancreatic β-cell function is a hallmark of T2DM progression. In fact, degeneration/apoptosis of Langerhans islets with β-cell loss is secondary to insulin resistance and is regarded as the key lesion for the progression of disease., As gradually there is decline in β-cell function, the impairment of insulin action becomes more prominent. Persistent hyperglycemia itself leads to detrimental effect on the secretory function "glucotoxicity," which enhances apoptosis in pancreatic islets. On the other, the abnormal lipid profile commonly seen in these subjects may be associated with functional impairment of the islet "lipotoxicity.",,,
The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study were the landmark studies, which emphasized on the benefits of intensive therapy in diabetes patients., The anti-diabetic therapies are designed to lower average high blood glucose to the levels approaching normal range so as to prevent or reduce the risks of complications.,, Oral anti-hyperglycemic drugs have an important role in the management of T2DM, where they act as a primary defence function against hyperglycemic events in comparison to insulin therapy. As the patterns in "oral anti-hyperglycemic drugs" has begun to change enormously around the world, it would be essential to conduct an investigation into the current trends that are being practiced in Eastern India. Therefore, this study is aimed to determine the pattern of drug prescribed among T2DM patients to collect the demographic details of these patients and to analyze the prescriptions according to prescribing indicators in a tertiary care teaching hospital in eastern India.
| Materials and Methods|| |
This was a prospective, observational, and noncomparative study conducted over a period of 12 weeks (August 2014 to October 2014) at medicine outpatient department in the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha. The study was carried out in 230 established T2DM patients after approval by the Institutional Ethics Committee. The informed consent was obtained from all the patients before conducting the study. The T2DM patients irrespective of age and sex, who were prescribed at least one oral anti-hyperglycemic medicine and visited outpatient's clinic were included in the present study. We excluded those diabetic patients, who were just admitted or were on in total insulin therapy or did not receive any drug therapy. The mentally unstable or challenged patients with gestational diabetes and patients unwilling to participate were excluded from this study.
The prescriptions were reviewed after the consultation by physician was over and selected study patients were interviewed using open structured questionnaire method. On each visit, information regarding use of medicines was given to the patients and all participants were advised to bring their remaining medicines and empty strips on the next visit along with drug purchase receipt from the pharmacy. The prescriptions were analyzed for the number of medicines prescribed, classes of medicines, generic drugs, which prescribed compliance and secondary failure. Some other data such as socio-demographic profile and relevant clinical data of participants were also recorded. Fasting (FBG) and postprandial blood glucose (PPBG) values were measured with a glucometer.
Among various available methods to assess the compliance, we used integration method. Every studied participant was interviewed regarding use of the medicines and residual tablet counting. The consumption of ≥80% of prescribed medicines was considered as compliance.
The obtained data were tabulated, analyzed, and the prescriptions were checked for suitability. The data were entered into Microsoft Office Excel 2007 and cross-confirmed for accuracy. Descriptive statistics for continuous variables were expressed as means and standard deviation (SD). Categorical variables were described as frequencies with percentages for the total sample.
| Results|| |
During the study period, a total of 283 patients selected to participate in this study. Out of these, 230 patients (response rate - 81.27%) willingly gave consent and participated. Female patients (n = 128, 55.65%) participated more as compared to male patients (n = 102, 44.35%). The mean age of the study population was found to be 54.66 ± 13.24 years. Overweight (98, 4.60%) and obese patients (53, 23.04%) contributed 151 (65.65%) out of total study population. The association of a positive family history of diabetes was found in 41 (17.82%) patients. The socio-demographic data of the study participants are shown in [Table 1]. A large number of patients, 82 (35.64%) was under the age of 50 years. Among them, 6 (2.60%) patients were below 30 years.
Hypertension (73.04%) was the most common co-morbidity followed by ischemic heart disease (31.73%) as shown in [Figure 1]. The mean duration of diabetes was 8.71 ± 7.78 years. Moreover, 45.21% of participants were following nonpharmacological measures (decreased carbohydrate intake, exercise, yoga, etc.,) along with pharmacotherapy. The clinical variables used were FBG and PPBG. Compliance to drugs and nondrug measures and the data on control of diabetes are shown in [Table 2].
The biguanide (85.21%) was the most commonly prescribed oral anti-hyperglycemic drug followed by sulfonylureas (58.26%). For the cardiovascular co-morbidities, the anti-platelet aggregation agents (73.04%) were most commonly prescribed, which was followed by statins (51.74%). The prescribing patterns of drugs in this study sample are shown in [Table 3].
The most frequently prescribed anti-hyperglycemic combinations in patients who received were glimepiride and metformin (53.47%), followed by metformin and voglibose (9.13%). [Figure 2] shows the distribution pattern of anti-hyperglycemic combinations. Single drug therapy was prescribed in 193 (83.91%) patients and combination of two drugs and three drugs were prescribed to138 (60.00%) and 17 (7.39%) of the patients, respectively [Figure 3].
|Figure 2: Distribution pattern of anti-hyperglycemic combinations (n=230)|
Click here to view
|Figure 3: Monotherapy and combination therapy of anti-hyperglycemic drugs prescribed in Type-2 diabetic patients|
Click here to view
The distribution of classes of anti-diabetic drugs prescribed in T2DM patients as monotherapy was 42.1% and combination therapy (biguanides – metformin) was combination therapy in 76.52% patients [Table 4].
|Table 4: Distribution of classes of anti-hyperglycemic drugs prescribed in type-2 diabetic patients as monotherapy and combination therapy|
Click here to view
The good compliance (≥80% consumption of the prescribed regimen) was observed only in 169 (73.47%) of the total number of patients. The female patients had good compliance as (75.78%) compared to males (70.58%). There was a better compliance with biguanides (83.67%) followed by thiazolidinediones (80.76%) and sulfonylureas (79.85%), only 13.04% cases showed a secondary failure in this study. The highest percentage of secondary failure was observed in the Glipizide group (15.38%), followed by metformin 8.67% [Table 5].
|Table 5: Patient compliance and secondary failure with oral anti-hyperglycemic drugs|
Click here to view
The average number of drugs per prescription was 7.01 ± 2.73 and only 4.66% of drugs were prescribed by generic name. Percentage of drugs prescribed from the WHO essential drugs list was, 26.17% and percentage of drugs prescribed from the National List of Essential Medicines of India, 2011, was 53.79%. [Table 6] describes the WHO core drug prescribing indicators. About 79.57% of prescriptions were according to the National Institute of Health and Clinical Excellence (NICE) guidelines of May 2009.
| Discussion|| |
Diabetes mellitus is a very fast growing major public-health challenge worldwide, as its prevalence is rising in many parts of the developing world. India is having the second largest diabetic population in the world. All diabetic patients deserve monitoring as the have to take lifelong medication and frequent evaluation. The compliances of diabetes can be prevented or delayed in their progression only by such compliance evaluation and tight glycemic control from the initial stage.,,
The mean ± SD age of patients in this study was 54.66 ± 13.24 years with a range between 23 and 98 years which was slightly higher than that reported in few studies carried out in India viz. 51.5 ± 12.3 years  and 50.4 ± 11.7. The range is comparable to other studies. The younger diabetic age group –25 of <40 years of age may be due to the lifestyle change in the younger population and also the stress factor which unmasks diabetes causing blood sugar to rise. Females (55.65%) predominated in the study population which was corresponding with other study results of India  and UAE.
Among the four educational status groups, the graduates (93, 40.43%) and illiterate (58, 25.21%) contributes to a significant proportion. The probable factors may be the nature of work, level of education, and economic status with a positive or a negative impact on the quality of life of and on the level of metabolic control. Satisfaction with treatment and quality of life are positively associated with job satisfaction and a higher income. People with lower education level and unemployed persons have, in general, a lower satisfaction with life and are less compliant with diabetes treatment, as well as have worse metabolic control. In the occupational types, the unemployed patients-housewives, student, retired, etc., had more prevalence of 66.52% and the low prevalence rate was found in nonsedentary job groups (10.43%); unlike the French study, there was no significant difference found. The uses of alcohol and cigarette smoking were not significantly reported in our study.
The mean duration of diabetes mellitus observed was 8.71 years which was slightly less than the mean values 11.4 years as reported in the United States duration study between 1997 and 2011. The incidence of complications was found to be lower in the patients with tight glycemic control in the beginning. The risks of developing complications are higher in long diabetic patients. The cardiovascular complications are the dangerous life threatening complication in diabetes. In this study, hypertension accounted for 73.04% of the total complications seen in the diabetes patients, followed by ischemic heart disease.
In the present study, metformin (85.21%), (biguanide) was the most commonly prescribed drug followed by sulfonylureas (58.26%). Another study from Nepal also reported biguanide and sulfonylureas as the most commonly prescribed oral anti-hyperglycemic drugs. It has been reported that the proportion of newly diagnosed patients initially treated with metformin increased from 51% to 65%, whereas those receiving sulfonylureas decreased from 26% to 18%. In the present study, we observed metformin alone was prescribed to 42.17% and metformin combination to 76.52% of the studied population. For the overweight and obese diabetic patients, metformin is considered as a drug of choice. Metformin acts as a peripheral sensitizer of insulin and also has good effects on insulin resistance, an important contributor in the pathogenesis of T2DM. It minimizes cardiovascular-related mortality rates more than sulfonylurea. Metformin does not stimulate insulin release so, it is not considered to produce severe hypoglycemia. Therefore, this study may be the one of the reason for the physicians to prefer metformin over other anti-diabetic drugs, with hypoglycemic risks.
Combination therapy was prescribed in a large number of patients (67.39%) to control diabetes. This was because of the progressive nature of T2DM as a metabolic disease, which is difficult to control. The physicians may have prescribed more combination drugs to control the blood glucose level in the T2DM patients. However on the other side, the fixed dose combination drugs may increase the problems such as drug duplication, chances of drug interaction and adverse drug reactions. A study showed an improved glycemic control with the combination of sulfonylureas to metformin, but a deterioration in control within 6 months. Therefore only the WHO approved fixed dose combination products are recommended and prescribed to such patients. The use of hospital formulary as approved by a competent pharmacy and therapeutic committee (PTC) is also recommended for rational anti-diabetic use of medicine. The lifestyle and dietary modification, regular physical exercise and measures of weight reduction are indicated for prevention of T2DM. PTCs of major hospitals need to conduct periodic surveys of anti-diabetic prescriptions.
The good compliance (≥80% intake of recommended dosage regimen) was shown only by 73.47% of the total study patients. The patients were more compliant towards biguanides (83.67%) followed by thiazolidinediones (80.76%), sulfonylureas (79.85%), and the least with sitagliptin 62.50%. There was 13.04% secondary failure in this study. The highest percentage of secondary failure was observed with glipizide 15.38%, followed by metformin 8.67%. The past studies have shown the highest compliance with sulfonylureas followed by metformin., The low levels of compliance was mainly affected by the factors such as age, family support and care, level of education, employment, place of residence, and daily dose regimen. All the diabetic patients should be counseled about the chronicity of the disease and dire consequences for noncompliance with the therapy. The other advice such as dietary modification and role of the exercise should be given and monitored in all diabetic patients.
The average number of drugs per prescription was 7.01 ± 2.73, which is high compared to the a study from UAE. The average number of drugs prescribed to studied population was high mainly because of other co-morbid illnesses of patients which require more medications. Inclination to brand name prescribing (95.44%) was extremely high than prescribing by generic names (4.66%). In an Indian study from Allahabad, it was reported that only 2% of the medicines were prescribed by generic names. The promotion of generic drugs could lead to cheaper treatment, low chance of drug duplication reduced interactions, and adverse drug reactions.
As we have studied only T2DM patients who are mainly on oral anti-hyperglycemic agents therefore, a low percentage of injection utilization was recorded in this study. The most common prescribed injection was insulin. This was given to those T2DM patients whose hyperglycemia was not controlled by oral drugs along with diet and exercise or in the condition when oral anti-hyperglycemics were not practicable or not tolerated or temporarily to tide over special conditions or any complication of diabetes.
| Conclusion|| |
The most frequently prescribed anti-hyperglycemic drug for T2DM was metformin. This study revealed that the pattern of oral anti-hyperglycemic prescription was rational and mostly compliant with NICE guidelines. This study indicates the clinical monitoring of the patient's compliance to the prescribed drug for achieving good glycemic control is also recommended, along with other comprehensive management such as life style changes, dietary modification, treatment of complications, and co-morbidities related to diabetes.
The authors are grateful to Dr. Manas Ranjan Naik, a senior scholar. We also thank SOA University for the resources and support.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, et al.
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011;378:31-40.
World Health Organization. Global Status Report on Non-communicable Diseases 2010. Geneva: World Health Organization; 2011.
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442.
World Health Organization. Definition, Diagnosis, and Classification of Diabetes Mellitus and Its Complications. Report of WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. Updated; 2006.
Centers for Disease Control and Prevention. National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2007. Updated; 2008.
Virally M, Blicklé JF, Girard J, Halimi S, Simon D, Guillausseau PJ. Type 2 diabetes mellitus: Epidemiology, pathophysiology, unmet needs and therapeutical perspectives. Diabetes Metab 2007;33:231-44.
Marchetti P, Lupi R, Del Guerra S, Bugliani M, Marselli L, Boggi U. The beta-cell in human type 2 diabetes. Adv Exp Med Biol 2010;654:501-14.
Kahn SE. The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus. Am J Med 2000;108 Suppl 6a: 2S-8S.
Poitout V, Robertson RP. Minireview: Secondary beta-cell failure in type 2 diabetes – A convergence of glucotoxicity and lipotoxicity. Endocrinology 2002;143:339-42.
Del Prato S. Role of glucotoxicity and lipotoxicity in the pathophysiology of type 2 diabetes mellitus and emerging treatment strategies. Diabet Med 2009;26:1185-92.
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-86.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53.
Shichiri M, Kishikawa H, Ohkubo Y, Wake N. Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000;23 Suppl 2:B21-9.
Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al.
Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-17.
Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: Beyond insulin and glucagon. Diabetes Spectr 2004;17:183-90.
American Diabetes Association. Standards of medical care in diabetes-2009. Diabetes Care 2009;32 Suppl 1:S13-61.
International Diabetes Federation. IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes. Brussels: International Diabetes Federation; 2005.
Sultana G, Kapur P, Aqil M, Alam MS, Pillai KK. Drug utilization of oral hypoglycemic agents in a university teaching hospital in India. J Clin Pharm Ther 2010;35:267-77.
Alam MS, Aqil M, Qadry SA, Kapur P, Pillai KK. Utilization pattern of oral hypoglycemic agents for diabetes mellitus type 2 patients attending out-patient department at a university hospital in New Delhi. Pharmacol Pharm 2014;5:636-45.
Hassan Y, Mathialagan A, Awaisu A, Aziz NA, Yahaya R, Salhani A. Trend in the use of oral hypoglycemic agents in an outpatient pharmacy department of a tertiary hospital in Malaysia (2003-2006). Asian J Pharm Clin Res 2009;2:40-6.
Santhosh YL, Naveen MR. Medication adherence behavior in chronic diseases like asthma and diabetes mellitus. Int J Pharm Pharm Sci 2011;3 Suppl 3:238-40.
Patel B, Oza B, Patel KP, Malhotra SD, Patel VJ. Pattern of antidiabetic drugs use in type-2 diabetic patients in a medicine outpatient clinic of a tertiary care teaching hospital. Int J Basic Clin Pharmacol 2013;2:485-91.
John LJ, Arifulla M, Sreedharan J, Muttappallymyalil J, Das R, John J, et al
. Age and gender-based utilization pattern of antidiabetic drugs in Ajman, UAE. Malays J Pharm Sci 2012;10:79-85.
Kurowska M, Tarach JS, Malicka J, Chitryn A, Dabrowska A. The impact of the level of education and paid work on HbA1c concentrations in patients with type 1 diabetes – Preliminary findings. Lublin-Polonia 2010; 23 Suppl 2:74-7.
Yusuff KB, Obe O, Joseph BY. Adherence to anti-diabetic drug therapy and self management practices among type-2 diabetics in Nigeria. Pharm World Sci 2008;30:876-83.
Mean and Median Distribution of Diabetes Duration among Adults Aged 18-79 Years, United States, 1997-2011. Diabetes Public Health Resource, Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/diabetes/statistics/duration/fig2.htm
. [Last accessed on 2014 Dec 13].
Das P, Das BP, Rauniar GP, Roy RK, Sharma SK. Drug utilization pattern and effectiveness analysis in diabetes mellitus at a tertiary care centre in eastern Nepal. Indian J Physiol Pharmacol 2011;55:272-80.
Desai NR, Shrank WH, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, et al.
Patterns of medication initiation in newly diagnosed diabetes mellitus: Quality and cost implications. Am J Med 2012;125:302.e1-7.
Cusi K, Defronzo RA. Metformin: A review of its metabolic effects. Diabetes Rev 1998;6:89-131.
Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care 2002;25:2244-8.
Cook MN, Girman CJ, Stein PP, Alexander CM, Holman RR. Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care 2005;28:995-1000.
Laakso M, Letho S. Epidemiology of macrovascular disease in diabetes. Diabetes Rev 1997;5:294-315.
Donnan PT, MacDonald TM, Morris AD. Adherence to prescribed oral hypoglycaemic medication in a population of patients with type 2 diabetes: A retrospective cohort study. Diabet Med 2002;19:279-84.
Boccuzzi SJ, Wogen J, Fox J, Sung JC, Shah AB, Kim J. Utilization of oral hypoglycemic agents in a drug-insured U.S. population. Diabetes Care 2001;24:1411-5.
Ansari KU, Singh S, Pandey RC. Evaluation of prescribing pattern of doctors for rational medicine therapy. Indian J Pharmacol 1998;30:43-6.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]