Anti-diabetic Drugs Utilization in Type 2 Diabetic Patients in AL-Nasiriya Governorate / Iraq

To study the utilization pattern of anti-diabetic drugs in type 2 diabetic patients and to evaluate the association of diabetes with demographic details and it's metabolic control. The study was carried out on 100 type 2 diabetic patients who visited ALNasiriya center for diabetes and endocrinology. Demographic details and complete prescriptions drugs, FBS (fasting blood sugar), HbA1c and BMI (body mass index) were recorded. A total of 100 type 2 diabetic patients, 27(27%) were males and 73(73%) were females. The greatest number of patients, 43%, were in the age group of 51-60 years. Obesity (BMI ≥ 30) were found in 51% of patients especially females 45(61.3%). Poor glycemic control (HbA1c ≥ 9) were found in 65% of the patients. Oral anti-diabetic drugs were prescribed in 53%, 16(60%) were males and 37 (50.6%) were females. Biguanide (metformin) alone, 22%, was the most common anti-diabetic drugs prescribed. Biguanides (metformin) and sulfonylurea combination, 19%, was the commonest anti-diabetic drugs combination. Insulin preparations alone were used in 23% of the patients and Novomix was the commonest type (10%). We concluded that oral anti-diabetic drugs were the most common prescribing drugs. Metformin was the commonest prescribing anti-diabetic drugs. Metformin and sulfonylurea being the most frequent combination prescribed. There were increasing in the use on insulin preparations in the treatment of type 2 diabetic patients. In achieving optimal glycemic control, the efficacy of anti-diabetic drugs was only 10%, planning of more intensification anti-diabetic treatment is necessary.


Introduction
Type 2 diabetes mellitus is a disease marked by high levels of blood glucose due to the action of insulin and insufficient insulin production. Type 2 diabetes accounts for approximately 90% to 95% of all diagnosed cases of diabetes [1]. Type 2 diabetes mellitus is one of the most common chronic conditions in the elderly [2]. Diabetes mellitus (DM) is one of the oldest diseases known to man, which was the first reported in Egyptian literature about 3000 years ago [3]. The Greek Physician Aretaeus  first gave the name diabetes. Avicenna, is the famous Arabian physician who first described the complication and progression of the disease [4].
Diabetes mellitus type 2 is a chronic disease characterized by coexisting insulin deficiency and insulin resistance, with the resultant hyperglycemia leading to micro and macro vascular complications [5,6]. Complications include altered metabolism of lipids, carbohydrates, protein and an increased risk of vascular disease complication [7,8].
The diagnosis of DM is based on the American Diabetes Association (ADA) guidelines or World Health Organization (WHO) national diabetic group criteria, which is for a single glucose reading with symptoms (polyuria, polydipsia, polyphagia and weight loss), or raised values on two occasions in asymptomatic patients [9,10].
Complications due to hyperglycemia in diabetes mellitus can be prevented by using rational use of oral antidiabetic drugs (OADs) and insulin [11].
Rational use of the drugs is a complex issue with a goal that is difficult to achieve, defined as follows: That patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements for an adequate period of time, and at the lowest cost to them and their community [12]. Rational use of the drugs in population can be effectively studied with drug utilization reviews. The World Health Organization (WHO) defines "drug utilization" as the marketing, distribution, prescription and use of the drugs in a society considering its consequences, either medical, social, and economic [13].
Various classes of anti-diabetic drugs including oral hypoglycemic agents (OHA) and insulin are currently used in the treatment of diabetes, which acts by different mechanisms to reduce the blood glucose levels to maintain optimal glycemic control [14,15].
The United Kingdom Prospective Diabetes Study showed intensive blood-glucose control by either sulfonylureas or insulin substantially decreased the risk of microvascular complications [16].
Because of the progressive nature of the disease, an evolving treatment strategy is therefore necessary to maintain both fasting and postprandial glycemic control. ADA and European Association for the Study of Diabetes (ESAD) Consensus recommended a target of HbA1c < 7% for good glucose control in clinical practice [17]. Selection of oral antidiabetic drugs as first line drug or combined therapy should be based on both the pharmacological properties of the compounds like efficacy, safety profile and also on the clinical characteristics of the patient like stage of disease, body weight, body mass index (BMI) [18]. More than 50% of people with diabetes have poor glycemic control and a large percentage have diabetic vascular complications [19].
United Kingdom Prospective Diabetes Study (UKPDS) advocates for increasing requirement of multiple therapies in patients with type 2 diabetes to achieve blood glucose target control [20]. Although the benefits of tight control of blood glucose have been well recognized and supported with evidences of several studies, the management of diabetes is complex, and considered to be not quite successful in a realworld setting [21,22].
A wide range of oral antidiabetic drugs such as sulfonylurea and biguanides have been used for since the last 50 years for the treatment of diabetes. The last decade and a half has seen the introduction of a number of oral antidiabetic drugs like Alpha-glucosidase inhibitors, thiazolidinediones, meglitinides and the most recently introduced dipeptidyl peptidase-4 (DPP-4) inhibitors [23]. A study on drug utilization can provide valuable information to the physicians, researchers to determine the drug use pattern [24].

Patients
The study was a retrospective study carried out in 100 established type 2 diabetic patients, age range from 40 -80 years who visited the Diabetic and Endocrinology center in AL-Nasiriya city during the time period of January 2015 to March 2015. Type 2 diabetes mellitus patients, irrespective of age and sex, who were prescribed one antidiabetic agents or more, were included in the present study.
Diagnosed type 2 diabetic patients who do not receive pharmacological therapy, prediabetic status, diabetic complications and serious medical conditions requiring subsequent hospital admissions were excluded from the study.

Material
Demographic data like age, sex, body weight, height, family history, detailed medical history, medications for diabetes mellitus, duration of treatment, concomitant medications for co-morbid disease, questions regarding lifestyle, dietary pattern, and exercise programme were recorded in this study. In addition, fasting, postprandial blood glucose and HbA1c was measured. Fasting blood sugar and postprandial blood glucose were measured by enzymatic method. HbA1c was measured by high performance liquid chromatography. Body mass index (BMI) was calculated as weight in kilograms divided by height in meter squared.

Statistical Analysis
The collected data were analyzed for their appropriateness and suitability and interpretation was made. Statistical analysis was done by SPSS (Version 11.2) software. Statistical methods used were simple frequencies and percentages.

Result
A total of 100 type 2 diabetic patients, 27 (27%) were male and 73 (73%) were female, were collected in the study during the period of 3 months as show in figure 1.  Table 1 show the demographic characteristics of the population studied. The table show the majority of the patients were found in the age group of 51-60 years, males were 13(48%) and females were 30(41%) as show in figure 2. Obesity (BMI ≥ 30) was found in the majority of the patients especially females, 45(61.3%) females and 6(23%) was males, as shown in figure 3.  Out of total 100 patients included in this study, the oral anti-diabetic drugs were the most commonly prescribed drugs, 16(60%) were male and 37(50.6%) were female. 5(18.5%) male and 18(24.7%) female were on insulin alone while 6(21.5%) male and 18(24.7%) female were on combined oral and insulin therapy, as shown in figure 5.  Table 2 show the types of anti-diabetic therapy were used by the patients studied and their relation to the glycemic control. The majority (53%) of the patients were prescribed oral antidiabetic drugs. Metformin (biguanide) only was the most common individual oral anti-diabetic drugs to be prescribed 22%, followed by a combination of Metformin and sulfonylurea 19%, followed by combination of metformin and dipeptidyl peptidase 4 inhibitors (DDP-4 inhibitors) 8%, and sulfonylurea alone was 4% (as shown in figure 6).
Insulin preparations alone accounted for 23% of the total anti-diabetic drugs and the most common preparation was premixed insulin (novomix) 10% (as shown in figure 7).
Combined oral and injectable anti-diabetic drugs were 24%, and the metformin (biguanide) and premixed preparation of insulin were the most common combined treatment were used (as shown in figure 8).

Discussion
Out of 100 patients evaluated in this study, 27(27%) were males and 73(73%) were females. Females predominated in the study population which agree with the result of a study in Taiwan, which show that the females are the predominate sex [25].
Out of 100 patients evaluated in this study, 43(43%) {13(48%) were males and 30(41%) were females} were found in 51-60 years of age group, this result was similar to a study of Roy V et al (1998) [26]. Greater prevalence in this age group may be due to change in life style, lack of physical exercise and stress [27].
The majority of males 11(40%) in our study with BMI ≥ 25 kg/m² (overweight) and 45(61.3%) females with a BMI ≥ 30 kg/m² (obese), which in itself is a well-recognized significant risk factor for diabetes mellitus.
It was found that among 100 patients with type 2 diabetes mellitus, 22(22%) were prescribed Metformin alone, which was similar with other studies [27,28]. This prescription pattern is according to guidelines of American Diabetes Association. They recommend that metformin should be started along with lifestyle changes at the time of diagnosis [34].
In this study, it was found that oral combination therapy was a common prescription pattern, 19(19%) patients, which was a common finding seen with study of V. Sivasankari et al., and Das P et al., (2011) which also suggest combination of biguanides and sulfonylurea was most frequently used combination and most effective one [35,36]. Co-prescription of a biguanides and sulfonylurea is a common practice [27].
The study documented low prescribing frequency of newer oral anti-diabetic drugs (DDP-4 inhibitors). They were used in combination with other oral anti-diabetic drugs mainly biguanides to achieve better glycemic control which was similar to other studies [31,37].
Insulin preparations alone accounted for 23% of the total anti-diabetic drugs and the most common preparation was novomix insulin 10(10%). Our study showed a higher percentage of insulin use compared with other studies [32,38].
The present study shows that 24% received insulin in combination with oral anti-diabetic drugs, which are similar to other study [38].

Conclusion
Oral anti-diabetic drugs were the most common prescribing drugs. Metformin was the commonest prescribing anti-diabetic drugs. Metformin and sulfonylurea being the most frequent combination prescribed. There were increasing in the use on insulin preparations in the treatment of type 2 diabetic patients. In achieving optimal glycemic control, the efficacy of anti-diabetic drugs was only 10%, planning of more intensification anti-diabetic treatment is necessary.