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COVER LETTER FOR SUBMISSION OF A PAPER TO TJNPR

[Kiki Rawitri]
[Department of Pharmacology, Faculty of Pharmacy, University of Sumatera Utara, Medan, Indonesia]
[Jl. Tri Dharma, Padang Bulan, Kec. Medan Baru, Kota Medan, Sumatera Utara 20115]

[20th Desember 2020]

Dear Prof. Abiodun Falodun, PhD

I/We wish to submit a new manuscript entitled “The Correlation Of Medication Adherence To
Clinical Outcomes And Quality Of Life For Type 2 Diabetes Mellitus Patients” for consideration
by the Tropical Journal of Natural Product Research.

I am submitting a manuscript for consideration of publication in Tropical Journal of Natural

Product Research. The manuscript is entitled “The Correlation Of Medication Adherence To
Clinical Outcomes And Quality Of Life For Type 2 Diabetes Mellitus Patients”. This manuscript
has been presented on Virtual Conference of the 3nd International Conference on
Pharmaceutical and Clinical Research (ICPCR) on November 25-26, 2020. We have no
conflicts of interest to disclose. Please address all correspondence concerning this manuscript to
me at khairunnisa7@usu.ac.id
Thank you for your consideration of this manuscript.

Thank you very much for your consideration.

Yours Sincerely,

Kiki Rawitri
Department of Pharmacology, Faculty of Pharmacy

Sincerely,

Kiki Rawitri
The Correlation Of Medication Adherence To Clinical Outcomes And Quality Of Life For

Type 2 Diabetes Mellitus Patients

Kiki Rawitri1, Khairunnisa1*, Wiryanto1

1
Department of Pharmacology, Faculty of Pharmacy, University of Sumatera Utara, Medan, Indonesia

*Email: khairunnisa7@usu.ac.id

Abstract

Diabetes mellitus (DM) patients are patients with a low level of medication adherence. Low
adherence can cause blood sugar levels to be uncontrolled properly, causing chronic
complications, and can affect the patient's quality of life. This study aimed to determine the
correlation between medication adherence to clinical outcomes and quality of life of type 2 DM patients.
This study used a cross-sectional study design involving 40 types 2 DM patients who met the inclusion
criteria at a community pharmacy in Medan city from August - September 2020. Compliance level data
were obtained using the MMAS-8 (Morisky Medication Adherence Scale-8) questionnaire, data on
random blood glucose levels and HbA1C values were obtained from direct examination of patients, and
data on patient quality of life were obtained using the EQ-5D-3L questionnaire. The data were analyzed
using the Spearman Rho correlation test. The results showed that the average patient had a low level of
adherence with an average HbA1C value of 9.1%, random blood glucose of 280 mg/dl, and quality of life
of 84.7%. The results of the correlation test showed a significant relationship between the level of
adherence and clinical outcome with a moderate correlation value at random blood glucose (r = -0.591)
and a strong correlation value on HbA1C (r = -0.817). The relationship between the level of adherence
and quality of life had a weak correlation value (r = 0.233), this indicates that the quality of life can
improve with increasing medication adherence. Based on the results of the study, it can be concluded that
the level of patient medication adherence greatly affects the clinical outcome and quality of life of type 2
DM patients.
Keywords: Type 2 diabetes mellitus, Adherence, Clinical outcome, Quality of life.

Introduction
Diabetes is one of four major non-communicable diseases affecting health problems globally. 1

The prevalence of diabetes sufferers globally increases by 51% with the composition of the

number of diabetes sufferers in 2019 as many as 463 million people, estimated to be 578 million

people in 2030 and 700 million people in 2045. The number of deaths caused by diabetes

mellitus (DM) is 1.6 million in 2016 and more than 4 million in 2019.2

In Indonesia, based on Basic Health Research (RISKESDAS) data, DM sufferers increased from

6.9% in 2013 to 10.9% in 2018.3 According to the International Diabetes Federation (IDF),
Indonesia is the sixth highest in the world who has DM sufferers with a total of 10.3 million in

2017 and is estimated to be 16.7 million in 2045.4

Diabetes mellitus (DM) is a group of metabolic diseases characterized by an increase in blood

glucose levels (hyperglycemia) as a result of insufficient insulin secretion, insulin action, or

both.2,5,6 Management of diabetes requires a complex treatment regimen and lifestyle changes to

improve adherence to treatment.7,8 Similar to patients with other chronic conditions, patients with

diabetes have poor adherence to medication.9,10

Medication adherence is the patient's compliance with the recommendation for the medication

that has been prescribed in terms of time, dose, and frequency. One of the factors that play a role

in the failure to control blood glucose in type 2 diabetes mellitus patients is the factor of patient

noncompliance with medication.11 Low adherence causes poor glycemic control, thus increasing

the risk of various chronic complications (microvascular and macrovascular). The consequences

will have a negative impact both economically, clinically, and on the patient's quality of life.12

The treatment success is influenced by patient adherence to treatment which is a major factor of

therapy outcome.13 Efforts to prevent complications in diabetes mellitus patients can be done by

increasing adherence to maximize therapy outcomes and improve quality of life. 5 This study

aims to determine the relationship between medication adherence to clinical outcomes and

quality of life for type 2 DM patients.

Materials and Methods

Study design

This study used an observational method with a cross-sectional study design. The study was

conducted at one of the pharmacies in the city of Medan in August-September 2020. This study

was approved by the University of Sumatera Utara Faculty of Nursing Health Research Ethics
Commission Number 2177/VII/SP/2020. All patients who participated in this research signed

and informed consent as evidence of willingness to become respondents.

Participants

The subjects of this study were 40 patients with type 2 diabetes mellitus. Inclusion criteria for

patients who were respondents included: 1) patients with a diagnosis of type 2 diabetes mellitus

for more than 3 months, 2) male and female patients aged> 18 years, 3) patients with type 2

diabetes mellitus with or without complications and comorbidities, 4) willing to take part in the

research by signing informed consent. Patient exclusion criteria included: 1) patients who were

not willing to be research subjects, 2) patients with mental disorders and pregnant women, 3)

patients with complications from chronic kidney disease (CKD), liver disease, Human

Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV/AIDS), and Tuberculosis

(TBC), 4) patients cannot communicate with pharmacists.

Data collection

Patient characteristic data collected included gender, age, educational status, employment status,

duration of illness, and comorbidity. Data on medication adherence and quality of life were

obtained through interviews with patients when taking medication at a pharmacy, while data on

HbA1C values and random blood glucose levels were obtained from direct examination of

patients.

Instrument

level of compliance

Medication adherence was assessed using an eight-item Morisky Medication Adherence Scale

(MMAS).14 The MMAS scale has been used for many chronic diseases including diabetes, as a

self-reported measure of adherence to prescribed medication. MMAS-8 is available in language

version and showed good validity (r = 0.869) and reliability internal consistency with a

Cronbach’s alpha of 0.806.15 Respondents were classified as having low adherence if their score

was less than 6, medium adherence if their score was 6 or 7, and high adherence if their score

was 8.

quality of life

One of the questionnaires to assess the quality of life is the European Quality of Life-5

Dimensions 3 Level version (EQ-5D-3L) instrument issued by EuroQol from the UK. 16 This

questionnaire has 5 dimensions, namely, 1) mobility/walking, 2) care. self, 3) usual activities, 4)

pain/discomfort, 5) anxiety/depression with each dimension having 3 levels of questions, namely

1) no problem, 2) little problem, and 3) problematic. Each level in the dimension has a different

coefficient. A value of 100% or 1,000 indicates perfect health. The scoring of the EQ5D

questionnaire was followed by the conversion of the EQ5D dimensions to the EQ5D Index, the

scoring of the EQ5D questionnaires was carried out by looking at the single summary index

value on each dimension. Then the transformed score will be carried out to be standardized in the

calculation of the EQ5D index.17

clinical outcome

Clinical outcomes include random blood glucose levels measured using an Easy Touch Dual

Function® glucometer and HbA1C measured using the BioHermes HbA1C EZ 2.0

Glycohemoglobin Analyzer HbA1C® device.

Statistical analysis

Each patient characteristic consisting of gender, age, educational status, employment status,

duration of illness, and comorbidity was analyzed using the univariate analysis to describe

descriptively the frequency distribution of each variable. The Spearman Rho correlation test was
used to determine the correlation between the level of adherence to clinical outcomes and quality

of life for patients with type 2 diabetes mellitus.

Results and Discussion

This study involved 40 types 2 diabetes mellitus patients who were conducted at a pharmacy

community in Medan City from August to September 2020 who met the inclusion criteria.

Characteristics of type 2 DM patients based on gender, age, education level, occupation, duration

of illness, and comorbid diseases can be seen in Table 1.

Table 1. Characteristics of type 2 DM patients

Variable Category Frequency Percentage

(N = 40)
Gender Male 17 42.5 %
Female 23 57.5 %
Age <45 years 2 5.0 %
45-65 years 37 92.5 %
>65 years 1 2.5 %
Educational status Primary education 3 7.5 %
Secondary school 6 15.0 %
Higher education 19 47.5 %
University 12 30.0 %
Employment status Civil servant/Government employed 7 17.5 %
Private/Merchant/Laborer 18 45.0 %
unemployed 10 25.0 %
Retired 5 12.5 %
Duration of illness <1 year 7 17.5 %
1-5 years 18 45.0 %
>5 years 15 37.5 %
Comorbidity Present 30 75.0 %
Absent 10 25.0 %

Table 1 showed that the majority of type 2 DM patients were women (57.5%) with the

productive age group 45-65 years (92.5%). Physically, women have a greater chance to increase

the body mass index, monthly cycle syndrome (premenstrual syndrome), and post-menopause

made it easy to accumulate in the body as a result of the hormonal process. Therefore, the
prevalence of DM in women is higher than in men. 18 The American Diabetes Association states

that people over 45 years old have more chance to develop disease19.

Most of the respondents' education level has moderate education level (high school 47.5%) and

tertiary education (30%) with the majority of jobs as private employees, traders, or laborers

(45%). The results of research by Sihombing et al. 2018 show there was no correlation between

the level of education and the occurrence of type 2 DM. The patients with high education are

supposed to have a greater concern for their health. In reality, highly educated people ignore

their health for varied reasons, one of which is the overloaded works and activities that

ultimately lead to unorganized lifestyles and health problems.18 Basically, controlling blood

sugar depends on individual awareness and compliance through life style.20

The percentage of type 2 DM which has a duration of illness less than 5 years is more (45%)

when compared to those with a duration of more than 5 years (37.5%). This is in line with

research conducted by Wijaya et al. 2015 that most patients suffer from diabetes mellitus in the

1-5 years range (39.14%).21 The duration of suffering from diabetes mellitus often does not

describe the actual disease process. This is because there are so many diabetes mellitus patients

who are diagnosed when they have complications, even though the disease process has been

going on for years before but has not been diagnosed.

Based on comorbidities suffered by type 2 DM patients, the results showed that patients with

type 2 DM had comorbidities as much as 75%. The majority of comorbidities suffered by type 2

DM patients are hypertension. In patients with type 2 diabetes, hypertension is often part of the

metabolic syndrome of insulin resistance.22 Hypertension may appear for several years in patients

before type 2 DM appears.

Description of Medication Adherence Level of Type 2 DM Patients

Patient medication adherence was measured using the MMAS-8 questionnaire. An overview of

the level of medication adherence to type 2 DM patients can be seen in Table 2.

Table 2. an Overview of the Level of Medication Adherence to Type 2 DM Patients

Compliance level Frequency (N = 40) Percentage

Low (1-5) 22 55.0 %
Moderate (6-7) 17 42.5 %
High (8) 1 2.5 %

Table 2 showed that from a total of 40 patients, 22 people had a low level of adherence, 17

people had a moderate level of adherence, and 1 person had a high level of adherence. Patients

with low levels of adherence have the largest number of patients with a percentage of 55.0%.

These results are in line with research conducted by Rasdiana et al. 2016, that type 2 DM

patients are classified as low adherence levels and most of the therapies undertaken by

respondents tend to be unsuccessful (uncontrolled blood glucose). According to him, the factors

causing the patient's non-compliance with the DM therapy being undertaken were busy activities,

running out of medication, forgetting to take medication, and feeling healthy so there was no

need to take medication.23

Correlation between Medication Adherence Level and Clinical Outcome (HbA1C Value and
Random Blood Glucose Levels)
The level of medication adherence was correlated with the clinical outcome of type 2 DM

patients. The clinical outcomes reviewed in this study were HbA1C values and blood glucose

levels at the time of the patient. The correlation between the level of medication adherence and

clinical outcomes can be seen in Table 3.

Table 3. Correlation between medication adherence level and clinical outcome (HbA1C values
and random blood glucose levels).
 Adherence N (%) Clinical Outcome r-value P-value
Score HbA1C Random HbA1C Random HbA1C Random
Mean (SD) Mean blood glucose blood blood
(SD) Mean (SD) glucose glucose
5.35 40 9,1 % 280 mg/dl -0.817 -0.591 0.000* 0.000*
(1.252) (100%) (1.239) (75.323)
Description: Spearman Rho analysis; * statistical significance (P <0.05)
Based on Table 3, the results of statistical tests using the Spearman Rho correlation test showed

that the correlation between the adherence score with the current HbA1C and random blood

glucose was a negative correlation with the HbA1C correlation value (r = -0.817) and random

blood glucose (r = -0.591). This shows that the level of adherence has a strong relationship with

the value of HbA1C and a moderate relationship with random blood glucose. The higher the

level of patient adherence, the lower the HbA1C and random blood glucose values when

obtained.

Based on the results of the study, it was obtained an average adherence score of 5.35, this shows

that type 2 DM patients have an average low level of adherence. This is in line with the average

HbA1C value obtained, namely 9.1% and random blood glucose of 280 mg/dl which is still high.

This incident illustrates the patient's lack of attention to DM. According to the American

Diabetes Association (ADA), and HbA1C value <7% indicates good diabetes control, a value

≥of 7% indicates poor diabetes control. From the results of HbA1C, it can be seen that the

average value of glucose in the last 1-3 months.19 Compliance level was associated with HbA1C

values, the better the adherence to the medical regimen, the lower the patient's HbA1C values.

Good adherence was associated with a 10% lower total HbA1C value 24. This finding also has an

important clinical impact for the patients with the associated reduced risks of microvascular

complications, as a previous study suggests that a one-percentage-point reduction in HbA1C (eg,

from 9.0% to 8.0%) results in a 35% reduction in complications of type 2 DM.25

In line with this, compliance is closely related to blood glucose levels. The higher the level of

patient compliance, the blood glucose level will decrease, conversely, the lower the patient's

medication adherence, the blood glucose level cannot be controlled, which means that the blood

glucose level will remain high.26

The Correlation between Medication Adherence Level to Quality of Life

The correlation between medication adherence level to quality of life can be seen in Table 3.

Table 3. The Correlation between Medication Adherence Level to Quality of Life

Adherence N (%) Quality of Life % r-value P-value

Score Index Quality
Mean (SD) Mean (SD) of Life
5.35 (1.252) 40 (100 %) 0.84 (0.123) 84% 0.233 0.149*
Description: Spearman Rho analysis; * statistical significance (P >0.05)
Based on Table 3, the mean EQ-5D index score in this study was 0.84, is lower than that

reported for the Indonesian general population at 0.91. 27 This is in line with the results of a meta-

analysis study by Lung et al. 2011, which found that the average values for individual health

states ranged from 0.81 for diabetic patients with no complications28.

Furthermore, a previous study by Perwitasari et al. 2017 in Indonesian type 2 DM outpatients (n

= 86) reported that the EQ-5D index score was 0.75 (SD 0.22). 29 Notably, Perwitasari et al. used

similar methods to measure and analyze the data, i.e., the EQ-5D-3L instrument, but with type 2

DM patients who have complications.

Based on Table 3, the statistical results of the Spearman Rho correlation test show that the

correlation between the compliance score and quality of life is a positive correlation with a weak

correlation value (r = 0.233) and a significance value of P> 0.05. This is in line with the research

of Martínez et al. 2008 which states that the level of adherence does not have a significant
relationship with quality of life, but together with trigger factors such as good knowledge and

positive behavior can improve quality of life.30

Conclusion
Based on the results of the study, it can be concluded that the average patient had a low level of

adherence with an average HbA1C value of 9.1%, random blood glucose of 280 mg/dl, and quality of life

of 84.7%. There is a significant relationship between the level of adherence and clinical outcome with a

moderate correlation value at random blood glucose and a strong correlation value on HbA1C. The

relationship between the level of adherence and quality of life had a weak correlation value, this indicates

that the quality of life can improve with increasing medication adherence. The level of patient

medication adherence greatly affects the clinical outcome and quality of life of type 2 DM

patients.

Conflict of Interest

The authors have no conflict of interest to declare.

Acknowledgement

The author would like to thank the master program of pharmaceutical science University of Sumatera

Utara and all parties involved in the process of data collection and data analysis.

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