October
2007 NEWSLETTER
INSULIN
ANALOGUES
HOW MUCH MORE EVIDENCE DO WE NEED?
Let’s take a look at the evidence now in the public domain:
·
Human insulins are not superior to animal insulin - Cochrane
Review, 2002
·
Rapid-acting insulin analogues have only minor
benefit for the majority of patients - Cochrane Review, 2004
·
Rapid-acting insulin analogues are not superior to human insulin for the
treatment of Type 2 - the Institute for Quality and Cost Effectiveness in the Health
Care Sector [IQWiG], July 2006
· Rapid-acting insulin
analogues are not superior to human insulin for the
treatment of adults with Type 1 diabetes. The benefits for children and
adolescents are unclear for lack of data - IQWiG, June 2007
·
Long-acting analogue insulins can be used as
an option for people with Type 1 diabetes but not for those with type 2
diabetes, except under special circumstances - NICE guidance, 2002.
·
Long-acting insulin analogues are not listed
for treatment of Type 1 and Type 2 diabetes because they are not superior to
NPH human insulin - Canadian Expert Drug Advisory Committee [CEDAC], June and
Sept 2005.
·
Long-acting insulin analogues have only minor
benefit, if at all, for the treatment of Type 2 diabetes - Cochrane Review, April
2007.
It is reasonable to say that there is little evidence that insulin
analogues are superior to their predecessors but is this lack of superiority
important?
It may not seem so to some but this is not the case. Already 40% of
people with diabetes have had their insulin changed unnecessarily, according to
the evidence above and the newly diagnosed are automatically being treated with
analogues, all at a significantly higher cost. So on what basis are analogues
being prescribed? Assumptions? Sales hype from the insulin manufacturers to
hook people on to the only insulins still in patent which can therefore be sold
at a higher price and greater profit?
So insulin analogues have no benefits over previous insulins but what
about their risks? Their long-term safety has not been established, they have
always had the potential for carcinogenic effects and there is growing evidence
of their mitogenic effects [cell multiplication which could lead to tumours].
So now there are real grounds to question whether these risks, high or low, are
worth taking for analogue insulins that are not superior to their predecessors
and more expensive. Compared to health risks, cost is less important but
Professor Edwin Gale questions whether people with diabetes are getting the
best deal when the choice is between treating 150-200 patients with long-acting
analogues instead of human insulin or employing a full time specialist nurse
educator at the same cost. [Diabetologia (20070 50:1783-1790]
While IDDT has been asking these questions since the introduction of
human insulin, they must be answered and sooner rather than later. In
discontinuing animal insulin and announcing the intention to discontinue human
insulins, manufacturers are foisting insulin analogues upon us. Sadly in
diabetes the choice of treatment has never truly rested with patients but soon
it will not be our doctors that are making our treatment decisions but drug
companies. This is unacceptable, harmful and sets a dangerous precedent for
healthcare.
IDDT
GOES TO
Progress
Report
Supplies of
Wockhardt Hypurin Pork insulins
IDDT
has followed up reports of difficulties obtaining Hypurin Porcine insulins and
on each occasion and the majority of the times, Wockhardt has the insulin in
stock and the problems are with misinformation from the pharmacy wholesaler.
Misinformation
about future availability of pork insulin
Many
people are being told by doctors, nurses and pharmacists that ALL animal
insulins are no longer available – not so, it is only Novo Nordisk that have
chosen to do this. Wockhardt has sent information to GPs, hospital diabetes
clinics and PCTs but the misinformation continues! On further enquiry, part of
the problem is that several GP and pharmacy databases are incorrect. We have pursued this with the Dept of Health
and Wockhardt.
Meeting at the Dept
of Health,
This
was chaired by Dr Sue Roberts, National Clinical Director for Diabetes and
attended by the Chief Executives of Novo Nordisk and Wockhardt and a representative
of Diabetes
·
Wockhardt confirmed their intention to continue to
provide animal insulins. They have bought in several years-worth of the raw
materials for which IDDT expressed gratitude!
·
The
misinformation problems were aired and the Dept of Health is now following up
the issues of misinformation on professional databases with vigour.
NICE assessing all
insulins
·
Early Day Motion
535 tabled by Sandra Gidley MP – this called for NICE to assess all the
insulins to provide the necessary information for patients and doctors to make
informed choices. 107 MPs signed the EDM and many others supported it by
raising the issues at Ministerial level.
·
The All Party
Parliamentary Group agreed
to take forward a briefing paper prepared by IDDT and the then Minister of
Health, Andy Burnham agreed to ask NICE to carry out an assessment of all
insulins. When nothing happened another Health Minister,
IDDT Meeting [
Jenny
explained IDDT’s philosophy that people with diabetes should have an informed
choice of treatment, be involved in decision-making about their own care. The
lack of choice of animal insulin, people not being listened to and even being
denied this choice, goes against these principles. Also that our request for
NICE to assess all insulins is part of this philosophy to ensure that informed
choice is available, including the risks of new analogue insulins and that
treatment is cost effective eg if 150 people were prescribed an equally
effective but cheaper human or animal insulin, another nurse could be employed
to help with education and provide better care.
Dr
Roberts was very open with what she hopes to achieve – a better outcomes
equation, organised proactive services in partnership with engaged empowered
patients to achieve better outcomes for people with diabetes. If achieved, very
similar to IDDT’s philosophy and one that will result in people having the
choice of animal insulins! She is discussing diabetes-related topics with NICE
and would like to meet regularly with IDDT to discuss progress and any concerns
we have. A meeting is to be arranged in November/December this year.
Let’s mark our
success!
·
We have an open ended commitment from
Wockhardt that they will continue to produce animal insulins.
·
We are now in direct and regular communication
with Dr Sue Roberts who understands and listens to the needs of people with
diabetes and even IDDT!
None
of this would have been possible without our members, so many thanks for your
enthusiastic support, determination and for writing numerous letters to MPs. I
would also like to thank the many MPs who have supported us and especially
members of the All Party Parliamentary Group for Diabetes, its Chairman Adrian
Sanders MP and Earl Howe, Conservative Spokesman for Health in the House of
Lords.
APOLOGIES FOR THE MISUNDERSTANDING!
In
IDDT’s July Newsletter there was a short piece ‘While on the subject of holidays’ in which one of our members was
concerned that the security measures at airports may prevent his wife from
obtaining the Lucozade she always takes to treat her hypos. My response was
that she could obtain a ‘full-blown’ Coke, any other sugary drink or a
chocolate bar. I got a couple of comments about this advice, especially the
chocolate because of its fat content! I know this is not standard advice for
treating a hypo but I was trying to point out [1] that in emergency, anything
sweet will do and [2] hypos don’t always have to be treated with the same
thing. Most people develop their own ways of dealing with hypos but in
emergency, it may be a case of whatever is available! Sorry for the
misunderstanding.
MORE ABOUT INSULIN ANALOGUES
Long-acting
insulin analogues have mitogenic and antiapoptotic activities
Before
reading further we ordinary mortals need some explanation of the terms.
·
Apoptosis
is the normal self-termination of a cell’s life to become replaced by another
one, so antiapoptosis is the opposite.
·
Mitogenicity is the promotion of division and
proliferation of any cell, including malignant and non-malignant tumour cells.
·
IGF-1 [insulin-like growth factor] is a hormone
with a range of effects - promotion of cell survival, cell proliferation,
inhibition of apoptosis, stimulation of metabolism.
The title of this research [ref1] sounds
complicated, so I’ll do my best to explain!
It has been known since their introduction, that
insulin analogues have similarities to insulin-like growth factor [IGF-1] so
might function differently from normal insulin and could cause cell
multiplication [mitogenicity] – hence their potential to cause tumours.
This research tested whether the two long-acting
analogues, Lantus [glargine] and Levemir [determir], show IGF-1 like activities
including enhanced mitogenic and antiaopoptotic effects.
The results: both Lantus and Levemir show potent mitogenic and
antiapoptotic activities which are significantly greater than those of human
insulin and seem to resemble IGF-1 action.
The researchers comment: this
supplements the work by Eckhardt et al which found that all insulin analogues
tested were more mitogenic than insulin and this mitogenic effect was greater
in cells from patients with a high IGF-1 receptor system expression so putting
such patients at greater risk than those with a low IGF-1 receptor system
expression.
Note: this research is continuing and is being funded by
IDDT as part of the policy to address uncertainties in insulin treatment.
Ref
1 Doron Weinstein, Zvi Laron, Haim Werner. Long-acting insulin analogues have
mitogenic and antiapoptotic activities. US Endocrine Society Meeting,
Ref 2 Kristian Eckardt, Claudia May, Marlis Koenen,
Juergen Eckel. Enhanced Mitogenic Potency of Insulin Analogs in Human
Fibroplasts and Smooth Muscle Cells is mediated by IGF-l Receptor Signaling
Diabetes, ADA Diabetes Care, June 2006 Vol 55 Suppl 1 463-P
New Review - Rapid-acting analogues are not superior to ‘human’ insulin for Type 1 diabetes
Yet again we are reliant on
The insulins investigated were, Humalog
[lispro], NovoRapid [aspart] and Apidra [glulisine].
What did the review find?
·
Adults -
there is currently no evidence available to demonstrate a superiority of rapid-acting
insulin analogues in the treatment of adults with Type 1 diabetes. The value of
the evidence and design of studies so far are inadequate and do not allow
conclusions regarding most important patient goals, such as the reduction in
long-term complications or overall mortality.
·
Children and adolescents – due to lack
of data, the benefit of rapid-acting insulin analogues in children and
adolescents is unclear [an uncertainty!]. Novo Nordisk has carried out
long-term comparative studies in this group of patients but they are
withholding some of the results.
·
Pump therapy – no long-term studies were available therefore it
remains unclear whether adults would benefit and what advantage patients would
have by using analogues with insulin pumps [an uncertainty!]. The same applies
to children and adolescents as only fully published short-term studies are
available. Novo Nordisk sponsored 2 long-term studies in children and
adolescents but to date, both studies have only been partially published and
unlike Sanofi-Aventis and Lilly, Novo Nordisk were not prepared to provide the
information needed for the review.
·
Quality of life, not a fair comparison – in
some studies patients treated with insulin analogues assessed their quality of
life as higher and they were more satisfied with treatment than those using
human insulin. IQWiG did not evaluate this finding as evidence of an additional
benefit, because it was not based on a fair comparison – patients in the human
insulin group were asked to adhere to a fixed injection-meal regimes but the
analogue group were not. [As we know, it is quite possible to use a flexible
regime with all types of insulin.] So it is unclear whether the patient
satisfaction was due to the insulin or to the more flexible regime prescribed
by the physicians.
What conclusions can be drawn from this?
Basically it is simple, there is no evidence that
rapid-acting insulins are any better than human insulins for adults with type 1
diabetes. It is unclear whether they are of any benefit to children and
adolescents. It is also unclear whether they are of benefit any groups of pump
users. They are, of course, significantly more expensive to the NHS! So once
more, this review raises big questions:
·
Why is the Dept of Health so unwilling to follow
·
Why are Primary Care Trusts that are so obviously short of funds,
spending unnecessary amounts on insulin analogues that have no proven benefits
over less expensive human and animal insulins?
·
Why are adults and children with diabetes being changed to insulin
analogues when they have no proven benefit?
·
Could all this be anything to do with heavy marketing of insulin
analogues because they are the only insulins in patent, therefore more
expensive and more profitable?
And by the way, a touch of curiosity: why was Novo
Nordisk unwilling to provide the necessary information to IQWiG?
Ref
1 Rapid-acting insulin analogues versus human insulin
in type 1 diabetes, the Institute for Quality and Cost Effectiveness in the
Health Care Sector [IQWiG],
TAKING MORE AND
MORE MEDICATIONS
IDDT is frequently contacted by people expressing concerns
that they are being advised to take more and more medications. Some are
concerned that all drugs can cause side effects, while others simply do not
want to take more drugs than absolutely necessary, especially if the evidence
of benefit has not been shown. Here is an example…………..
ACE
inhibitors to protect the kidneys
ACE Inhibitors are normally used to treat raised blood
pressure [hypertension] but increasingly they are being prescribed to people
with diabetes to protect their kidneys, even if they have normal blood
pressure. It has been shown that both ACE inhibitors and
angiotensin receptor-blockers (ARBs) are effective treatments for people with
hypertension, early diabetic nephropathy, or both [ref 1]. But does
this mean that all people with diabetes should be put on one of these drugs?
According
to Dr B Hirsh [ref 1], most people put on ACE inhibitors for renal protection
do OK. However, the evidence for using ACE inhibitors for this reason was
from a study of mostly people with Type 2 diabetes over the age of 55
[MICRO-HOPE trial published in 2000]. This showed that use of the ACE inhibitor, ramipril,
significantly reduced the combined outcome of myocardial infarction,
stroke, or cardiovascular death by 25%. But do the results of this
study apply to younger people with Type 1 diabetes where the drug is
being used to protect the kidneys?
There
are no randomised controlled trials investigating ACE inhibitors for
the prevention of diabetic renal disease in people with normal blood pressure
and relatively good blood sugar control. Dr Hirsh also says that he is unaware
of any recommendations by any diabetes or kidney society for this
use. So although ACE inhibitors are prescribed frequently for kidney protection
to people without raised blood pressure, this is based on assumptions of
benefit not evidence of benefit – yet another uncertainty in the treatment of
people with diabetes.
Dr Hirsh makes 3
key points:
Note:
these statements also apply to the widespread recommendations that people with
diabetes over the age of 40 should take statins and aspirin – not everyone can
tolerate them.
Example: one of our
members with blood pressure the low side of normal but a small amount of
protein in her urine [microalbuminuria] was prescribed ACE inhibitors to
protect her kidneys but they lowered her blood pressure so that she fainted and
frequently felt lighted-headed. She was unsafe to drive, not because of
hypoglycaemia, but from the use of ACE inhibitors to protect her kidneys!
Recommendations: ‘Ask about
Medicines’ supported by the Dept of Health recommends people to always ask
questions about any new medications, why they are necessary, what are the side
effects and what evidence there is that they are safe and effective.
Ref 1
SOURCING INFORMATION
Patient information
leaflets - available to people with visual impairment
Patient
Information Leaflets [PILs] are the leaflets found inside packs of medicines.
For those with internet access, PILs are available for all
A
new service is available for people who are blind or visually impaired - called
X-PIL. The X-PIL website www.medicines.org.uk/XPIL.aspx
provides a number of electronic formats:
·
the
original package insert
·
in
large font [18-22 point]
·
in
a version that can be used by a screen reader
Over
the coming months over 2,500 PILs will be available on the X-PIL web site and
by the end of 2007 PILs will also be available in audio MP3 format. You can
also listen to a PIL by telephoning the Royal National Institute of the Blind
[RNIB] Medicines Information Line (tel 0800 198 5000). You can also request
PILs in a number of different formats - large/clear print, Braille or on audio
CD.
Many
of us use the internet as a source of information, sometimes as our main
source. Searching for health information is no exception to this but we do have
to be aware that there are some not very reliable websites. A
In
questionnaires and interviews, the study investigated 800 recently
diagnosed cancer patients' and 200 carers'
use of, and attitudes to, the internet as a source of information compared with
other sources. The average age of patients was 63 and of carers 43.
·
4.8%
of patients but 48% of carers accessed the internet directly for cancer
information.
·
Helplines
had a low use [2.9% of patients and 19.3% of carers] which the authors describe
as not cost effective.
·
Carers
were more likely to seek information for themselves, possibly as a way of
coping, but patients were more likely to use information chosen by someone else
and wanted the hospital doctor to provide internet sites. There was a high
usage of sites recommended by doctors.
·
Use
of internet information was low in ethnic minorities.
·
High
levels of satisfaction were reported for internet information rating it higher
than booklets or leaflets.
The
authors concluded that the internet is an effective source of information for
those who use it.
Ref
1: 'A Study of information seeking by cancer patients and their carers,'
Clinical Oncology, vol. 19, June 2007
HYPERTENSION
Up to 65% of people with diabetes, both Type 1 and
Type 2, have hypertension – raised blood pressure. It is caused by
atherosclerosis, a thickening of the blood vessel walls narrowing the blood
vessels so that blood flow is restricted. Long-term high blood pressure
increases the risks of other diabetic complications such as stroke, coronary
artery disease, retinopathy and nephropathy [kidney damage].
Blood pressure measurements
The numbers that are given as your
blood pressure results eg 130 over 80
are systolic and diastolic pressure readings. The systolic reading, the
top figure, is your blood pressure as your heart beats and the diastolic is the
pressure between beats. With hypertension, both systolic and diastolic readings
may be high, or the systolic alone may be high but both types can lead to
serious complications if not treated.
Presently normal blood pressure is
defined as 120/80 mmHg for people without diabetes and 130/80 mmHg for those
with diabetes and/or chronic kidney disease but these definitions can vary in
different countries.
Symptoms
Usually there are no symptoms with mild
or moderately high blood pressure so it is important to have your blood
pressure checked regularly. Many people now use home blood pressure testing
kits but it is advisable to talk to your doctor about this. If blood pressure
is extremely high the following symptoms can occur:
Treatment
Medications that may be prescribed to
reduce blood pressure include diuretics [often called water tablets],
angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers,
beta-blockers, and calcium channel blockers. It is also often recommended that
adults with diabetes take aspirin daily.
Note: recent research
[ref1] has recommended that doctors stop routinely
using beta-blockers to control high blood pressure as other hypertension pills
work better and cause fewer side effects eg fatigue and sexual dysfunction. For
many years beta-blockers and diuretics were the standard treatment for high
blood pressure but evidence is now suggesting that diuretics and newer
blood-pressure medications are superior. Beta blockers work by blocking the
effect of adrenaline on the heart which slows down the heart so that it does
not have to work as hard, so the researchers emphasise that there is strong
evidence to support the use of beta-blockers in people who have had a heart
attack or those with progressive heart failure.
Prevention
Ref 1 Journal of the
WINTER'S COMING AND SO ARE COLDS
Flu’ and pneumonia
jabs.
Don’t
forget that people with diabetes are seen as priorities for both the flu’ jab
and vaccination against pneumonia – both are free.
The common cold
Rhinoviruses
are responsible for about half of all common colds in children and adults.
School children usually catch between 7 and 10 colds a year, and adults
Echinacea 'can
prevent a cold'
Taking
the herbal remedy echinacea can more than halve the risk of catching a common
cold, according to
Echinacea
is a collection of nine related plant species indigenous to
The
researchers found that more than 800 products containing echinacea were
available, and that differing parts of the plant, flower, stem and root, were
used in different products. They said more work was needed to check the safety
of these different formulations.
Professor
Ron Cutler, of the
People
with Type 1 diabetes have an impaired immune system, so it may be worth
thinking about taking echinacea but as with all herbal remedies, you should
discuss this with your doctor.
COULD
YOU HELP WITH RESEARCH?
·
Do you have Type 1 diabetes? Are you aged 21 - 36 and
were diagnosed between the ages of 12 and 16?
·
Would you be prepared to talk about your experiences?
Emily
Deacon, Trainee Counselling Psychologist at
To
find out more, contact Emily on: tel 07815964199 or emilydeacon@yahoo.co.uk
EDUCATION, EDUCATION, EDUCATION!
Nurses identify
barriers to good self-management and strategies to overcome them
If
you don't understand the title it means what stops us, people with diabetes,
from achieving 'good' management of our diabetes. This was addressed at an
American symposium [ref1] of 50 nurses and other health professionals. I don't
know about readers, but I find this irritating before I even start to read what
they actually think - it may be well intentioned but it seems patronising and
judgmental to not involve the views of people with diabetes.
Having
said this, most of the barriers they identified were not the fault of patients
but the fault of health systems. While these are views of health professionals
in
·
difficulty
navigating the healthcare system
·
the
lack of self-care education following diagnosis
·
limited
time with healthcare providers
·
under-valuation
of the importance of patient education
·
the
complexity of diabetes education
·
inadequate
patient health literacy.
None
of these 6 points are the fault of patients, not even the last one - they are
the fault of the health systems that are supposed to provide treatment, care
and education.
The
symposium’s solutions to these problems all centred around the importance of
education - need for more time with health professionals, developing better approaches to teaching
self-management and research to show the value of patient education [do we
really need yet more research on what is obvious?]. Finally they concluded that
health professionals "need to assume
that patients have a low level of health literacy and to use media other than
print, such as DVDs, in the educational process." Thanks a bunch! No
problems with using DVDs etc - they are very useful as they can be watched over
and over again but please don't assume that all patients have a low level of
health literacy - this really is patronising!
Has the term
'education' made the situation worse?
In
terms of ‘education’ we have to look at Type 1 and Type 2 diabetes separately -
they are different conditions that require different information and different
approaches.
If
we look back at Type 1 diabetes 30 years ago, we didn't have diabetes
specialist nurses, we didn't have many doctors who were specialists in diabetes
and paediatricians who specialised in diabetes were a rarity. But we did have
'patient education' although it was rarely referred to as such - in fact it was
automatically all part of diagnosis and treatment.
You
only have to attend an IDDT Conference to see that people who have had Type 1
diabetes a long time know how to count carbohydrates, know about the value of
exercise. If blood sugars are high, they don't simply inject more insulin but
mow the lawn or go for a long walk. They understand the relationship between
insulin, carbs and exercise. All this was achieved as a natural part of being
diagnosed with diabetes, it wasn’t called ‘education’ and there was no need for
research to prove its cost effectiveness!
So when did all
this change and why?
There
is probably a whole range of reasons but some are obvious:
·
people
with Type 1 diabetes used to see their hospital clinic doctor at least
6monthly, and more often if necessary, with time to talk through any problems
and what adjustments to make – ongoing ‘education’ although it wasn’t seen as
such. Now there is an annual MOT - less time with a specialist doctor and less
time for education. Moving people with Type 1 diabetes from hospital clinics to
GP surgeries has had questionable benefits, as many people report that they
know more than the GP!
·
Replacing
carb counting with 'healthy eating' in the late 1980s meant that people
received less 'education' about diet. Learning to count carbs automatically
meant learning to understand adjusting insulin and the relationship with
exercise. That carb counting is now
being seen as the way forward, DAFNE courses etc, brings a wry smile to some
us, but sadly there is a whole generation of people with diabetes and health
professionals who have an information gap that needs filling.