A Better World for Diabetics
Advances in non-intrusive insulin delivery methods are sure
to bring sweet relief to diabetic community in India. Jayata Sharma gives
an insight into ongoing research that aims to transform diabetes management
The accompanying picture shows the
computer rendition of insulin hexamer. It was composed by Lukasz Komsta
of Department of Medicinal Chemistry of Medical University of Lublin,
Recently, Novo Nordisk, a leading insulin pen manufacturer,
introduced their latest insulin penLevemir. Almost simultaneously, Medtronic
India, that has been selling insulin pumps for the last three years in the Indian
market, unveiled their advanced pumpMiniMed Paradigm REALTime System.
In the last one year, India has seen a slew of insulin pens and pumps. Not surprising,
if you consider the fact that most studies peg Indians as more prone to diabetes
than almost any other population in the world. Also, the world over diabetes
is seen as a big threat in the coming years and many innovative and non-invasive
methods of insulin administration are under development by various companies.
These advances are being eagerly supported by diabetologists, despite their
being concerns over safety, efficacy and cost.
The latest to capture the imagination of diabetologists are oral pills and insulin
inhalers. As insulin breaks down in the digestive system, research is on to
develop an alternate method of transporting insulin and protect it from breaking
down. Bangalore-based Biocon has the patent for conducting this research. And
according Dr Subodh Kanchi, Medical Advisor, Biocon, "Research on oral
and inhaled insulin is in Phase I on humans. While these modes of delivery
still seem years away, patients today can benefit from many alternatives to
Alternatives to needle!
pens are preferred as they are painless, easy to administer and convenient
for the patient"
- Dr Archana Juneja
Diabetologist, Wockhardt Hospital
An insulin pen is fast on its way to become the predominant
insulin delivery system in most of the world. "Insulin pens are painless,
easy to administer and convenient for the patient," says Dr Archana Juneja,
Diabetologist, Wockhardt Hospital, Mumbai. A patient just has to punch in the
desired dose and then push the top of the pen to inject insulin through a 31-gauge
needle into the subcutaneous tissue, from where it is absorbed into the circulatory
system. A pen has components like cartridge, cartridge holder, outer needle
shield, needle, dose window, dose knob, injection button, pen cap, click dial
mechanism, piston rod, cork supports, rotational screws and many other small
parts. New pens from companies like Eli Lilly and Novo Nordisk also have systems
to record the history of patient's insulin intake.
Both disposable and re-usable insulin pens can hold 300 units of insulin and
can be used for delivering various insulin combinations. Using pens is hassle-free
and ensures precise dosing. It also enhances patient compliance by overcoming
the psychological barrier of pain attached to conventional insulin syringes.
In an insulin pump, insulin is transferred to the patient on a continuous basis.
As big as a pager, a pump has a reservoir or cartridge for insulin, catheter,
and a computer chip regulating the flow of insulin. The catheter, also known
as infusion set or connecting device, is a thin plastic tube with a fine needle
at the end. The pump can be attached to the waist belt just like a mobile phone.
The catheter or the connecting tube of the pump is injected into the abdomen
and filled with the short/rapid acting insulin, which is to be disposed off
in three-four days. Insulin pumps are programmed electronically to deliver
the desired amount of insulin and usually, fast acting analogues like lispro
or aspart are used in the pumps," says Dr RK Lalwani, Diabetologist, Rockland
Hospital, New Delhi.
immediate results without any problems, patients now prefer closed loop
- Dr Manoj Chadha
Diabetologist, PD Hinduja Hospital Mumbai
Insulin pumps are of two types: In open loop pumps, the required
dosage is set through a gluco-monitor, while closed loop pumps do not require
active intervention but function more on the lines of natural production of
insulin. "Closed loop pumps have an in-built continuous glucose monitoring
system (CGMS), that ensures continuous delivery of insulin without the patient
having to actively monitor his glucose time and again," says Dr Manoj Chadha,
Diabetologist, PD Hinduja Hospital, Mumbai. An in-built algorithm in the pump
computes the amount of insulin to be administered. "Because of the convenience
and better glycaemic control, doctors prefer insulin pumps for all type 1 diabetics
and pregnant woman," says Dr V Mohan, Chairman, Dr Mohan's Diabetes Specialities
Centre & Madras Diabetes Research Foundation, Chennai.
Currently, Medtronic is the only company manufacturing and marketing closed
loop pumps in India. The glucose sensor in the MiniMed Paradigm REAL-Time
System, measures glucose levels in the interstitial fluid, as many as 288 times
a day, which is nearly 100 times more often than three daily fingerstick measurements,"
informs Milind Shah, Managing Director, Medtronic India. This method ensures
regular delivery of insulin and rules out human error, and in the long run pumps
ensure that serious medical problems are averted.
Introduced in the '80s, jet injectors have somehow not manged to find favour
within the diabetic community as is evident by their low market share of around
two per cent. "In jet injectors, insulin is pushed into the subcutaneous
tissue using pressure induced by jet injectors," says Dr Bandukwala Saifuddin
Mohamedally, Consultant Diabetologist and Cardiologist at Mumbai-based Dr LH
Available in India from two companies, Shreya and Roche, jet injectors cost
around Rs 14,000. The usage is low in India as they are reported to be a bit
cumbersome to use and cannot use more than 30 units of insulin. But, have do
have the significant advantage of causing less tissue damage, according to Dr
SK Wangnoo, Diabetologist with Delhi's Indraprastha Apollo Hospital.
Pulmonary or inhaled insulin seems to be the most promising
alternate route for insulin delivery. For the last three years, trials on inhaled
insulin are being conducted at Indraprastha Apollo Hospital in collaboration
with Eli Lilly. "We are currently doing research on insulin inhalers,"
says Dr A Ramachandran of MV Diabetes Hospital and Research Centre, Chennai.
Novo Nordisk is engaged in research on insulin inhalers, and plans to introduce
insulin inhalers in the Indian market by 2009. Pfizer Inc has already launched
an inhaled insulin called Exubera in the US and EU and is approved in both the
nations for adults with type 1 and type 2 diabetes. Nektar developed the inhaler
and the powder insulin formulation, while Pfizer is responsible for marketing
and promoting it. Exubera is a rapid-acting, dry powder human insulin that is
inhaled through the mouth into the lungs prior to eating, using the handheld
Exubera Inhaler. Because Exubera is inhaled, it may lower the lung function,
result in dry mouth, low blood pressure or chest discomfort. Diabetologists
are required to take a breathing test before recommending Exubera.
Patches that enable transdermal administration are still in
the phase of pharmacologic investigation. The goal is to perfect a 24-hour patch
that will provide a needle-free basal insulin supply to the body. One problem
in developing the patch is that insulin does not easily pass through the skin
due to its high molecular weight. In addition, analogues with longer duration
are being worked upon worldwide.
Ensures regular delivery of insulin and rules out human error. In the
long run pumps ensure that serious medical problems are averted.
- Prohibitive price!
- Not possible to combine different types of insulin.
Hassle-free and ensures precise dosing.
+ Enhances patient compliance by overcoming the
psychological barrier of pain attached to conventional insulin syringes.
- Patients still have to prick the skin for injecting
Less tissue damage.
- Cumbersome to use, cannot use more than 30 units
- Under test, might suffer due to low absorption
of the drug and high incidence of side effects.
Needle-free basal insulin supply to the body.
- Under test, insulin does not easily pass through
the skin due to its high-molecular weight.
What future holds
Randomised clinical trials are being conducted on oral, pulmonary insulin and
also on insulin pumps and continuous glucose monitoring devices at Dr Mohans.
Also on the anvil are insulin implants called pallets. However, some doctors
like Dr Kanchi feel, "Pens are here to stay. Alternatives will be a supportive
option for pens, and will help in reducing the number of injections to about
two per day. But there is good news in that area too as needles will also
become finer in the future. In addition to the 31-gauge needles, Novo Nordisk
plans to launch 32-gauge ones in India soon. Novo Nordisk already offers these
in the international market, but is working out a pricing for India.