International Journal of Research in Pharmacology & Pharmacotherapeutics

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1 344 International Journal of Research in Pharmacology & Pharmacotherapeutics Available online at Print ISSN: Online ISSN: IJRPP Volume 2 Issue Research article Study on Rational Use of Anti-Diabetic Drugs in Patients with Diabetes and Other Co-Morbidities *1 Sriram.S, 2 Senthilvel.N, 3 Merin.P, 4 Vidhya.D * 1 Prof & Head, Dept. of Pharmacy Practice, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Siddhapudur, Coimbatore, Tamil Nadu, India. 2 Senior Consultant-Physician, Department of General Medicine, Sri Ramakrishna Hospital, Coimbatore 3 Lecturer, Sri Krishna College, Trivandrum, India. 4 Lecturer, College of Pharmacy, SRIPMS, Coimbatore,Tamil Nadu, India. ABSTRACT India presently has the largest number of diabetic patients in world and has been infamously dubbed as the Diabetic capital of the world. The study was undertaken to know the prevalence of Diabetic population and to evaluate the prescriptions for rational use of Antidiabetic medications and the management of existing co-morbidities. A prospective-observational study was carried out in General Medicine Department of a private corporate hospital, for a period of eight months. Evaluation of prescriptions was done for rational use of antidiabetic drugs in diabetic patients with other co-morbidities. Patient Information Leaflet, Diabetic food Chart & Diabetic Diary were prepared and given to patients. Therapeutic guidelines was prepared and given to the relevant department. A total 93 diabetic patients were enrolled in the study. In 48% of the diabetic population Hypertension was the major co-morbidity. The major microvascular complications observed include diabetic nephropathy in 12 (12.93%) patients. The major category of antidiabetic drugs prescribed were insulin (64.4%), sulphonyl urea (40.0%) and biguanides (28.9%), α- glucosidase inhibitor prescribed was acarbose (17.8%).Thirty diabetic patients (32.26%) had two co-morbidities followed by 21 patients (22.58%) with one co-morbidity and 16 (17.2%) patients had three co-morbid condition. In patients with diabetes all drugs should be used with both potential risks and benefits in mind. Conversely, the drugs that lower blood sugars by inducing weight loss and lessening insulin resistance, thereby improving glycemic control and the patient s quality of life need to be prescribed. Pharmacists play a major role in helping the patient maintain control of their disease. KEYWORDS: Diabetes Mellitus, Co-morbidities, Antidiabetic drugs INTRODUCTION During the last 20 years, the prevalence of diabetes has increased dramatically. The International Diabetes Federation states that 246 million adults across the world have Diabetes mellitus. Diabetes accounts around six percentage of total mortality around the world, and 50% of diabetes- associated * Corresponding author: Sriram.S address: visitram@yahoo.com deaths being attributed to cardiovascular disease. Yearly on average 6, 25,000 newer diabetes cases are diagnosed and more than 180,000 deaths due to the disease and related complications. India presently has the largest number of diabetic patients in world and has been infamously dubbed as the Diabetic capital of the world. According to the International Diabetes

2 345 Federation (IDF), Diabetes Atlas (2006) was released at 19 th World Diabetes Congress, there were an estimated 40.9 million persons with diabetes in India and the number may rise up to 70 million people by The countries having the largest number of diabetic people will be India, USA and China and in It has been found that diabetes mellitus is the main cause of more than 11% of all new cases of blindness, more than one third of renal diseases, and half of non traumatic lower extremity amputations. Many evidences points that diabetes patients are having two to four times more chances to die from heart diseases and stroke. Due to progressive nature of type 2 diabetes mellitus (T2DM), many individuals require insulin to optimize glycemic control over time as oral hypoglycemic agents fail to achieve targets. Data from the UK Prospective Diabetes study suggest that 53% of patients will require insulin after 6 years following diagnosis and 75% of patients will need multiple treatments after 9 years. Even though insulin treatment is very effective in achieving glycemic control, use of insulin is associated with weight gain due to increased body fat mass, especially abdominal obesity. Obesity accounts greatly to insulin resistance, even in the absence of diabetes. In fact, weight loss is a corner stone of therapy for obese type 2 diabetic patients. [1] Two major types of heart and blood vessel disease, also called cardiovascular disease, are common in people with diabetes: coronary artery disease (CAD) and cerebral vascular disease. People with diabetes are also at risk for heart failure. Narrowing or blockage of the blood vessels in the legs, a condition called peripheral arterial disease, can also occur in people with diabetes. Diabetes is the most common cause of kidney failure, accounting for nearly 44 percent of new cases. Even when diabetes is controlled, the disease can lead to Chronic Kidney Diseases (CKD) and kidney failure. Over several years, people who are developing kidney disease will have small amounts of the blood protein albumin beginning to leak into their urine. This first stage of CKD is called microalbuminuria. The kidney s filtration function usually remains normal during this period. As the disease progresses, more albumin leaks into the urine. This stage may be called microalbuminuria or proteinuria. As the amount of albumin in the urine increases, the kidneys filtering function usually begins to drop. The body retains various wastes as filtration falls. As kidney damage develops, blood pressure often rises as well. Overall, kidney damage rarely occurs in the first 10 years of diabetes, and usually 15 to 25 years will pass before kidney failure occurs. [2] The pharmacist can play an important role in diabetes care by screening patients at high risk for diabetes, assessing patient health status and adherence to standards of care, educating patients to empower them to care for themselves, referring patients to other health care professionals as appropriate, and monitoring outcome. Pharmacists play a major role in helping the patient maintain control of their disease. The pharmacist can monitor the patient's blood glucose levels and keep a track of it. [3] METHODOLOGY This prospective-observational study was conducted in the General Medicine Department of a 700 bedded multi- specialty private corporate hospital. The reason for selection of this department was that, a pilot study done revealed more prevalence of diabetic cases in the department of General Medicine that has got lot of potential to use many classes of antidiabetic drugs. The study was carried out for a period of eight months. Approval provided by the hospital authority to use the hospital facilities was obtained. All the patients getting admitted to General Medicine Department with T1DM and T2DM along with other co morbid disease conditions were included in the study. Patients in the outpatient department and patients with incomplete case sheets were excluded from the study. Specially designed data entry format has been used to note down the cases from study site which included the details of patient s demographics, past medical history, laboratory investigations done, diagnosis and the drugs prescribed. All prescriptions for diabetes (with other co-morbid diseases) were evaluated for patient details like sex, age, obesity, laboratory investigations, self care assessment, co-morbid disease states, drugs prescribed, rationality of the prescriptions, complication associated and its management, drug interactions etc. Systemic hypertension was found to be the major co-morbidity (45%) associated with diabetes. Special study was

3 346 done on rationality and appropriateness of diabeticon management hypertensive study population. Patient information leaflet (Figure 1) of diabetes and diabetic diary (Figure 2) were provided to all the patients who were enrolled in the study. Diabetic diet chart which was prepared in consultation with the dietician of the study hospital was given to the patients with explanations for their easy reference. Figure1:Information Leaflet Figure 2: Diabetic Diary

4 347 RESULTS A total of ninety three diabetic patients were enrolled in the study. The prevalence of Type III diabetes were high i.e., 89 (97%) compared to Type I diabetic population which constitutes only 4 patients during the study. The age was 61.2±12.4 years (mean± S.D) and the duration of diabetes was 6.4±6.3 years (mean± S.D). Study results on major co-morbidity along with diabetes revealed that in 48 % of the diabetic population Systemic Hypertension was the major co-morbidity (Figure3). The major microvascular complications observed include diabetic nephropathy in 12 (12.93%) patients (Table 1). The major category of antidiabetic drugs prescribed to these patients were nsulin (64.4%) (Table 2), sulphonyl urea (40.0) and biguanides (28.9%), α-glucosidase inhibitor prescribed was acarbose (17.8%) (Table3). Number of co-morbidity Figure 3: Major Co- Morbidities is 2.23±1.03 (mean± S.D) and the major co-morbidity was found to be Systemic Hypertension in 45 patients (Table 4). This compelled the physician to prescribe more number of drugs which ultimately may have effect on the glycemic control of the patient. It was observed that in 22 patients Insulin and Fluroquinolone combination were seen which requires close monitoring of glucose level and adjustment in the dose of antidiabetic agents. The percentage of diabetic hypertensive patients who could achieve target blood pressure of < 130/80 mm of Hg was 46.7% (Table 5). Study on the rational use of drugs revealed that there are drugs which were prescribed with wrong frequency of administration. Acarbose which should be prescribed thrice daily was prescribed only once a day and frusemide which is to be prescribed in twice daily dose was also prescribed only once daily. Table 1: Micro Vascular Complications (n=93) Category No: Of Patients (%) Diabetic Neuropathy 6 (6.45) Diabetic Nephropathy 12 (12.93) Diabetic Retinopathy 1(1.07) Diabetic Foot 6 (6.45)

5 348 Table 2: Categorization of Antidiabetic Drugs Prescribed (n=93) Antidiabetic drug No of Patients (%) Insulin Therapy 54 (58.06) Insulin + Single OHA 9 (9.67) Single OHA Therapy 9 (9.67) Combined OHA Therapy 12 (12.90) Insulin+ Combined OHA Therapy 4 (4.30) Table 3: OHA Prescribed (n=93) OHA NO: OF PATIENTS (%) Acarbose 3(3.22) Metformin 15(16.12) Glimepride 6(6.45) Glipizide 2(2.15) Glibenclamide 2(2.15) Metformin + Glimepride 7(7.52) Pioglitazone + Glimepride 1(1.07) Glipizide + Metformin 1(1.07) Glibenclamide + Metformin 1(1.07) Glimepride+Pioglitazone 1(1.07) +Metformin Table 4: Major Co-morbidity (Systemic Hypertension) Baseline Characteristics (n=45) S.NO CHARACTER AVERAGE 1 Age yrs 2 Years of HT 5.98 yrs 3 SBP mmHg 4 DBP 86.50mmHg 5 Years of DM 8.16 yrs 6 FBS 139 mg/dl 7 RBS mg/dl Table 5: Blood Pressure of Diabetic Hypertensive Patients According To Type of Therapy Received (n = 45) PATIENTS ON Mono therapy (n = 31) Multiple therapy (n = 14) NO: PATIENTS WITH SBP (MM OF HG) NO: PATIENTS WITH DBP (MM OF HG) <130 % >130 % <80 % >80 %

6 349 DISCUSSION A total of ninety three diabetic patients were enrolled in the study of which 65 (70%) were male and 28 (30 %) were female population. Similar study conducted by Venmans M.A.J [4] also showed more male population (55%) compared to female (45%). By calculating the Body Mass Index using the height and weight of the patient, they were categorized as Obese or Non Obese. Of the 93 patients screened 21 (22.58%) were in obese category with body mass index more than 30 and the remaining 72 were in non-obese category. The social status details from the standard data entry format revealed that around 41% of the patients screened were smokers and 21% were alcoholics. (Table 6) The prevalence of Type II diabetes were high i.e., 89 (97%) compared to Type I diabetic population which constitutes only 4 patients during the study. The age categorization study revealed that between the age of 51-65, the late adulthood age patients were more (48%) followed by adulthood (17%),This is comparable with other study done by Vijay [6]which shows that more number of diabetic patients were in age frequency. Out of four Types I cases in two patients there were early onset of diabetes and was during adolescent age. According to the present study results on major comorbidity along with diabetes revealed that in 48% of the diabetic population Systemic Hypertension was the major co-morbidity similar study conducted by Robert Chilton et.al also reveals that 75% of the diabetics study population had hypertension. [7] In type 2 diabetes hypertension is likely to be present as a part of the metabolic syndrome (i.e., obesity, hyperglycaemia, dyslipidemia) that is followed by high rates of CVD [8]. The other major comorbidities were respiratory tract infection in 18 patients (22.5%). Bronchial asthma in 15 patients ( 16%),Ischemic heart disease in 11 patients (11.8 %) and Urinary tract infection in 14 patients (15%).The major microvascular complications include diabetic nephropathy in 12 (12.93%) patients, followed by diabetic neuropathy and diabetic foot, both in six patients. The major macrovascular complications were systemic hypertension in 45 patients (48.38%), followed by Ischemic heart disease and congestive heart failure in 18 patients (19.35%) and stroke in 7 (7.52%) patients. This is comparable with study conducted by American Diabetes Association [8] stating nephropathy and hypertension are the major microvascular and macrovascular complications respectively. It was found that 35 patients in the study population had diabetes between one to four years of duration and 23 (24.73%) had for a duration between 5 to 10 years. Six patients had diabetes for more than 20 years. 12 (12.9%) patients were diagnosed as diabetics very recently i.e. within one year and six were newly diagnosed. The major lab investigations done included fasting blood sugar ( 65%).Similar study conducted by Sarwar et.al [9] shows that more number of lab investigations were done for FBS and random blood sugar levels (78%) followed by renal function test in 61 (65%), blood counts estimation in 56 patients (60.21%) urine examination in 39% and electrolytes in 27 % of population. The study on the major category of Antidiabetic drug prescribed includes Insulin therapy in 54 (58%).This is comparable with study of Denis R [10] shows that more number of the patients were on insulin therapy. Exogenous insulin therapy is rationale to compensate for secretory failure of beta cells in the presence of marked insulin resistance. Hence insulin therapy may be used as an alternative to oral drugs after its failure or contraindication [11]. Diabetes mellitus Insulin- Glucose infusion in Acute Myocardial Infarction (DIGAMI) study documented a beneficial cardiovascular effect of intensive insulin therapy in the year following myocardial infarction. Combined oral Hypoglycemic drugs were given in 12 patients. Nine patients received single OHA therapy and combination of insulin and OHA for 4 patients. Of all OHA prescribed, the biguanides, Metformin was prescribed in 15 (16.12%) patients. Metformin is a peripheral sensitizer of insulin and has beneficial effects on insulin resistance; an important factor in the pathogenesis of type 2 diabetes [12]. Metformin was followed by Glimepride in 6 patients (6.45%). Similar study done by G Sultana et.al [12] shows that metformin and glimepride were the mostly prescribed OHA s respectively. The other category of drugs prescribed include Antibiotics in 68 (73.18%), Anti hyperlipidemic drugs in 47 (50.53%), followed by NSAIDS in 43(46.23%) and antihypertensives in 42 (45.16%) patients. Thirty diabetic patients (32.26%) had two comorbidities followed by 21 patients (22.58%) with

7 350 one co-morbidity and 16 (17.2%) of patients had three co-morbid condition during the study period. This compelled the physician to prescribe more number of drugs which ultimately may have effect on the glycemic control of the patient. It was observed that in 22 patients Insulin and Fluroquinolone combination were seen which requires close monitoring of glucose level and adjustment in the dose of antidiabetic agents. There were 45 patients who met the inclusion criteria for Diabetes Mellitus with Hypertension as comorbidity. The average age was years old and 53% were male. The mean duration of hypertension was 5.98 years and mean duration of diabetes was 8.16 years (Table 4). The percentage of diabetic hypertensive patients who could achieve target blood pressure of < 130/80 mm of Hg was 46.7%. The blood pressure control of patients receiving monotherapy & multiple drug therapy were analyzed. Systolic blood pressure control was 39% in patients on monotherapy, 64% in patients receiving multi drug regimens. Diastolic blood pressure control was 32% in patients on monotherapy, 43% in patients receiving multiple Table 6: Patient Characteristics (n=93) therapies. The major categories of antidiabetic drugs prescribed to these patients were insulin (64.4%), sulphonyl urea (40.0%), biguanides (28.9%), α- glucosidase inhibitor (17.8%) and thiazolidinediones (04.4%). Metformin (28.9%) was the only biguanides prescribed. α-glucosidase inhibitor prescribed was acarbose (17.8%). A total of 31 patients (68.9%) received monotherapy and 14 (31.1%) received combination therapy. Major monotherapy to treat diabetes was insulin in 21(46.7%) patients. The baseline characteristic studies done on 45 patients who are having hypertension as co-morbidity revealed that the average fasting blood sugar value is 139mg/dl and the average random blood sugar level is 206mg/dl. The major antihypertensive drug prescribed in type 2 diabetes patients were Telmisartan in 26 (57.8%) followed by Hydrochlothiazide in 25 (55.5%) of patients. Study on the rational use of drugs revealed that there are drugs which were prescribed with wrong frequency of administration. Acarbose which should be prescribed thrice daily was prescribed only once a day and frusemide which is to be prescribed in twice daily dose was also prescribed only once daily. Characteristics Category Statistical analysis value Gender Male Female 69.89% 30.10% Age Mean ± S.D 61.24±12.35 No. Of co-morbidity Mean ± S.D 2.23±1.03 Duration of diabetes Mean ± S.D 6.4±6.3 Alcohol Yes Smokers Yes GUIDELINES Once the diagnosis of diabetes has been established, the question of initiating therapy must be addressed. At this initial stage, the physician or healthcare professional who is seeing the patient should obtain a detailed history and perform a complete examination with appropriate laboratory testing. The future progression of the patient's care will be affected by a number of factors, including the physician's treatment philosophy, the patient's healthcare beliefs and competence at self-care, and the availability of a team consisting of a dietician, diabetes educator, exercise physiologist, and, when needed, social workers and psychologists The approach must consider the whole person with diabetes, not just the levels of glycemic control to be achieved or the therapy to be used to accomplish this

8 351 (i.e., insulin or oral antidiabetic therapies). To this end, a strong, integrated team approach is the one most likely to succeed. Although, as noted above, the complete team may not exist in most cases, the physician and the patient can make considerable progress together, with other components of the team, especially the diabetes educator and dietician, coming from the community. In diabetes care, lifestyle modification can prevent complications or markedly delay their appearance, as well as decreasing the need for medication. Pharmacist provided interventions help in the prevention of acute complications and reduce the risk of long-term complications. Table 7: General Information on OHA CONCLUSION This study shows the significance of including dietary modifications, strict glycemic control, cardiovascular prevention and treatment of complications and co-morbidity. In patients with diabetes all drugs should be used with both potential risks and benefits in mind. Conversely, the drugs that can lower blood sugars by inducing weight loss and lessening insulin resistance, thereby improving glycemic control and the patient s quality of life need to be prescribed. Many patients with type 2 diabetes have concomitant hypertension, hyperlipidemia, atherosclerosis, and coronary heart disease. Any drug that could complicate these conditions should be used cautiously under the direct supervision of a physician. Hypertension affects about 60% of patients with type 2 diabetes. More studies should be carried out in this particular area as serious cardiovascular events are more than twice as likely in patients with diabetes and hypertension as either disease alone.the benefits of tight blood pressure (BP) control in patients with diabetes are to be kept in mind while treating Diabetic patients. Measures should be taken to improve patient adherence to the prescribed studies. Drug interactions and cost minimization during prescribing antidiabetic drugs will enhance patient healthcare.

9 352 REFERENCE [1] David H et al. Pharmacy Cardiovascular Council Treatment and Guidelines for the Management of Type 2 Diabetes Mellitus: Toward Better Patient outcomes and New Roles for Pharmacist. Pharmacotherapy 2002; 22(4): [2] Rosemin K, Graydon S M. Role of Pharmacist on a Multidisciplinary Diabetes Team. Canadian Journal of Diabetes 2007; 31(3): [3] Subish P, Leelavathy D A, Padma G M, Ravi S, Nidin M N, Nibu N. Knowledge, Attitude, and Practice Outcomes: Evaluating the Impact of Counselling in Hospitalized Diabetic Patients in India. P&T 2006; 31(7):383. [4] Venman s MAJ, BL. Diabetics Pathophysiology. Armenian Medical Network. Available at: URL: [5] Lawrence B. Current antihyperglycemic treatment guidelines and algorithms for patients with Type 2 Diabetes Mellitus: The American Journal of Medicine (2010) 123, S12-S18. [6] Vijay M. Management of Diabetes in Chronic Renal Failure: Indian J Nephrology, 2005:15, S23-S27. [7] Robert C, Jamisen W, Shailesh N, Rene O, Michael L. Cardiovascular Co-morbidities of Type 2 Diabetes Mellitus: Defining the potential of Glucagon like peptide-1-based therapies. The American Journal of Medicine (2011):124-S 35- S53. [8] Skylar. Standards of Medical Care for Patients with Diabetes Mellitus: American Diabetes Association, 2003:26, S33-S50. [9] Sarwar N, Gao P. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease:a collaborative meta-analysis of 102 prospective studies :The Lancet: 2010:375, [10] Dennis R. Insulin Therapy In Patients With Type 2 Diabetes Mellitus: Treatment To Target Fasting And Postprandial Blood Glucose Level;Vol:1 No:4 2006: [11] Biswajit P, Goyal R K. Drug Therapy of Type 2 Diabetes Mellitus in the New Millennium: Int J Diabetes.2000; 8:8-16. [12] Sultana G, Kapur P, Aqil M, Alam MS, Pillai. K K. Drug Utilization of hypoglycemic agents in a university teaching hospital in India: J of Clinical Pharmacy and Therapeutics: 2010:35, *******************************