About194 million people worldwide, or 5.1%, in the age group 20-79were
estimated to have diabetesin 2003. This estimate is expected to increase
to some 333 million, or 6.3% of the adult population, by 2025. The largest
proportional and absolute increase will occur in developing countries,
where the prevalence will rise from 4.2 to 5.6% (International Diabetes
The number of people with diabetes is increasing due to population growth,
aging, urbanization and increasing prevalence of obesity and physical
inactivity (Sarah et al., 2004). It accounts for about one sixth
of all expenditures for health care.
The mortality rate in patients with diabetes may be up to 11 times higher
than in persons without the disease. Diabetes is a leading cause of blindness,
renal failure and foot and leg amputations in adults. Managed care and
budgeted resources challenge clinicians to provide comprehensive health
care to patients with diabetes (Joe and Bryan, 1999).
The Health economic condition is not very healthy in a developing country
like Pakistan. The monthly expenditure of an average Pakistani household
in 2004-05 was 9,121 rupees (152 USD); only 3.8% i.e., 346 rupees (5.7
USD) is spent on health reflecting the fact that health care is a low
priority for the majority of Pakistani households (Household Integrated
Economic Survey, 2001-2002).
The Diabetes Control and Complications Trial and the UK Prospective Diabetes
Study were benchmark studies that have shown that good glycaemic control
can reduce the risk of diabetic complications and poor outcomes (Lynda
et al., 2006).
Insulin therapy is often an important part of diabetes treatment since
its discovery in 1921. This discovery meant that people with diabetes
who were insulin-treated survived the acute effects of the disease (International
Diabetes Federation, 2006).
The major problem today lies in the widespread long-term lack of access
to insulin and diabetes supplies, which poses a serious threat to the
lives of people with diabetes in developing countries. For proper delivery
of diabetes care, insulin, insulin syringes and needles and othermonitoring
suppliesshould be available, accessible and affordable to all those who
require them (International Diabetes Federation, 2006).
The World Health Organization (WHO) estimates that 40% of people with
diabetes need oral medicines and 40% need insulin injections. However,
it is estimated that only 3% of people with diabetes in developing countries
are being treated. Insulin is particularly difficult to make available
because of the need for daily injections and its relatively high cost.
Insulin is difficult to manufacture to sufficiently consistent quality
for therapeutic use (WHO, 1998).
Data published by IDF recorded that an estimated 150 million vials of
insulin were produced yearly with the vast majority being used in developed
countries. Seventy percent of all insulin was used in countries that comprised
16% of the world`s population (Raab, 1999).
The price of insulin is influenced by many factors, including the original
price from the manufacturer, transport and storage costs, size of market,
the profit margins of distributors and retailers and government taxes.
It is frequently those most in need who are most adversely affected by
these factors-smaller countries with small markets and transport problems,
multiple intermediaries, excessive bureaucracy, tariffs and sometimes
corruption (Graham et al., 2006).
In the developed world and some developing countries, insulin is provided
free or at minimal cost by government health services or insurance arrangements.
Where, this is not so and the drug is not provided by charitable organizations,
insulin must be purchased at market or premium prices. A 10 mL vial of
100 U mL-1 insulin costs up to 1800 (30 USD). Assuming an average
price of 900 rupees (15 USD), a person with type 1 diabetes using 50 U
day-1 will use 18 vials/year-a cost of 16200 rupees (270 USD)/year.
This may exceed the family`s total annual income. The financial impact
is compounded by other components of care-syringes and needles, blood
glucose monitoring, consultation fees, travel expenses and missed work
days (Garham et al., 2006).
The majority of poor and even middle-class people in developing countries
do not have health insurance and are forced to pay for medicines as they
need them. Since diabetes is a lifelong condition, the cost of medicines
can drive people living with diabetes into a downward spiral of debt and
poverty (Mohga, 2003 ).
In 1982, the first genetically engineered product- human insulin using
E. coli bacteria- was approved for use by diabetics (Biotechnology
Institute, 2005). But in developing countries due to cost animal insulin
was still in use. Animal insulin is 50% cheaper than recombinant human
There was a need of relatively low cost human insulin in Pakistan. Highnoon
Laboratories, one of the leading National pharmaceutical company started
to import recombinant human insulin from China to Pakistan with the name
of Dongsulin in 2000. The price of Dongsulin was 13 to 31% lesser as compared
to the Recombinant human insulin marketed by multinational companies in
The objective of this study was to evaluate the effectiveness of Dongsulin
in maintaining HbA1c level over 3 months period in a normal clinical practice
setting and secondly to assess weight gain, episodes of hypoglycaemia,
insulin dose change and safety of dongsulin.
MATERIALS AND METHODS
It was an Open label phase 4 trial conducted at Baqai Institute of Diabetology
and Endocrinology, Karachi Pakistan from May 2006 to September 2006. A
written informed consent was obtained from all those patients who fulfilled
the inclusion criteria. The protocol was approved by the Institutional
Review Board (IRB) of BIDE. A total of 52 subjects with type 1 or type
2 diabetes already on commercially available (rDNA) human insulin at least
from last six months, were enrolled to a 12 week of treatment. HbA1c was
checked at the baseline visit and patients with HbA1c level between 6-8%
were switched from their current (rDNA) human insulin to Dongsulin on
same dosage. The patients were asked to check their blood glucose at home
as they were checking before. They were also, asked to follow the same
dietary and physical activity routine as they were following before. The
compliance of the patient regarding dietary pattern, physical activity
and insulin dosages were assessed at baseline and at the end of the study.
Patients known to have either of the noncompliance factors at the start
of the study was excluded from the study. After 12 weeks, the patients
had their HbA1c checked again. There were no essential planned visits
for the study; patients followed the clinic as they were doing previously
in normal clinical practice setting. Doses of insulin were adjusted according
to the blood glucose levels. Patients with pregnancy, hepatic or renal
impairment and with known hypersensitivity to Dongsulin or any of its
constituents were excluded from the study. Patients who were not compliant
to insulin dosage prescribed, dietary guidelines and physical activity
pattern during the study period were grouped as group B (non compliant)
while, patients who were compliant to all those factors were grouped as
group A (compliant).
RESULTS AND DISCUSSION
Out of 52 patients, 39 completed the study in which 64.1% (n = 25) were
females. 82.05% (n = 32) were having type 2 diabetes. Mean age of the
patients was 49±12 years (Table 1).
Group A (compliant) and B (non compliant) were consisting of 25 and 14
patients, respectively. No significant difference was found between the
HbA1c of two visits in group A (compliant) (p = 0.32) while, HbA1c in
group B (non compliant) was significantly raised as compared to first
visit (p = 0.000) (Table 2). While looking at the factors
affecting glycaemic control in group B (non compliant), it was found that
71.4% (n = 10) patients missed the doses, 78.5% (n = 11) patients made
significant changes in their diets and (n = 10) 71.4% patients decreased
their physical activity. The mean insulin dose and weight of the patients
remained the same between first and second visits in both groups as shown
in Fig. 1a and b. No major episode
of hypoglycemia was observed while 8% patient suffered from minor episodes
This study was carried out to assess the efficacy of newly available
economical recombinant rDNA human insulin (Dongsulin) in normal clinical
practice setting. It was observed that 25 out of 39 patients remained
compliant to insulin dosage, dietary guidelines given and exercise pattern
advice. These patients maintained their HbA1c at the end of study. While,
14 patients did not comply and hence, deterioration in their glycaemic
control as measured by HbA1c was observed.
Several factors i.e., dose missing, change in quality and quantity of
food and change in physical activity as shown by others in which glycaemic
control was not achieved even by increasing the number of OHAs for co-administration
or by insulin use unless dietary/exercise therapy, a basic therapeutic
option, was adequately used (Nippon, 2004).
|| Basic characteristic of the sample
* Percentage is reported
|| Comparison of HbA1c between 1st and 2nd visits in group
A and B
Almost three fourth of the patient in group B (non compliant) were missing
their insulin dose can lead to hyperglycemia (National Diabetes Information,
2004). Almost similar number of subjects (77%) were found to be inconsistent
to their diet intake and studies have shown that diet is an important
factor in glycemic control and variation to dietary guideline can lead
to increase in blood glucose levels (Mary and Frank, 2006).
The reasons leading to non compliance of previously compliant patients
would be many. Mango season, traveling as there were school summer vacation
and frequent marriage ceremony in the month preceding Ramadan, all could
contribute. This observational study has limitations. Moreover the information`s
collected at the time of the start of the study were subjective in nature.
The subjects were not followed intensively and the same routine of blood
sugar checking and follow-up was advised as they were doing before the
start of the study to avoid any bias in the study.
|| (A) Comparison of insulin doses between 1st and 2nd
visit [Group A (n = 25) and Group B (n = 14)] and (b) Comparison of
weight between 1st and 2nd visits [Group A (n = 25), Group B (n =
No significant change in the units of insulin was observed in group B
despite being poor glycaemic control, due to lack of blood glucose monitoring.
Those patients who followed after blood glucose checking were advised
to improve their compliance first.
This study has shown that patients who remained compliant during the
study period, switched over to Dongsulin had no significant change in
the glycaemic control as measured by HbA1c. Dongsulin was well tolerated
with no significant hypoglycaemic events. No significant change in weight
and dose requirement was noted. Since this study had limitations therefore
further single or double blinded studies are required to give us more
We are thankful to Highnoon Laboratories Limited for their support in