From: sbharris@ix.netcom.com (Steven B. Harris )
Subject: Re: Humulin U
Date: 20 Sep 1995
Newsgroups: sci.med

In <43pfuu$qe6@granite.sentex.net> jdnicoll@granite.sentex.net (James
Nicoll) writes:

>	My cat recently turned out to be diabetic and was prescribed
>Humulin. There was a slight delay in filling the prescription because the
>pharmacy I deal with was out -- apparently they almost never get a call
>for that particular brand of insulin *except* for animals suffering from
>diabetes. Forgive a stupid question, but why is that?
>
>								James Nicoll



   I don't know.  Humulin (human insulin made by bacteria with human
genes) is widely used, but maybe your pharmacy serves a population of
HMO types who must use the pork and beef insulins due to cheapness.
Pork insulin differs from human in one amino acid, and beef by three.
I don't know about cat and dog insulins, but perhaps they just happen
to be closer to human than they are to pork or beef, and this cuts
chances in pets of allergies, and loss of insulin effectiveness due to
antibody binding.  This is a *guess*.  Hopefully somebody who has
better vetrinary info will contribute.

                                                 Steve Harris, M.D.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,talk.politics.medicine
Subject: Re: me too drugs marketing darlings and little else
Date: 9 Sep 2005 19:27:01 -0700
Message-ID: <1126319221.884447.58510@z14g2000cwz.googlegroups.com>

fresh~horses wrote:
> From Colleen Fuller to SBH and SJ: on the issue of me-too drugs:
>
> Andre Picard does a great service to Canadians with his latest article
> describing "me-too" drugs that don't offer any new benefits over cheaper
> existing medicines.
> 
> People who use insulin are familiar with this routine in spades. In
> 1982, Canadian-made insulin cost between $6 and $8 a vial. That year a
> new type of genetically engineered insulin came on to the market at $18
> a vial, even though it provided no advantages over the many existing
> insulins that came from beef and pork.


COMMENT:

Except an insulin less likely to provoke anti-insulin antibodies, and
one free of the quality control problems of producing a product from
dead animals.


> Then in 1995, most of the cheaper insulins which had been on the market
> for decades were withdrawn altogether.

COMMENT:
Too generalized a statement to really argue with. Who did this and
where?  Beef insulin is no longer available due to mad cow disease.
Pork insulin is available just about everywhere, including Canada
(where about 200 Canadian still us it). This gets down to issues of why
you can't find vinyl record players or 8-track tapes anymore. The world
moves on.

> The next year, another new insulin was introduced at $30 a vial even
> though it didn't provide any significant advantages over existing
> cheaper products - cheaper now being the genetically-engineered brands
> at $19 to $23 a vial.

COMMENT:
Too few specifics to comment on.



> Studies of the latest insulin to hit the market, Lantus, have not shown
> any significant advantages over existing brands, but it costs $60 a
> vial, thus setting a new and much higher bar on the cost of insulin.

COMMENT:
There's finally a specific. There are medical trials showing advantages
of the ultra-long acting insulin Lantus (glargine). Where's your
evidence it has no place in treatment of any population of diabetics?
I'll be glad to post an abstract on the "pro" end. You do the same.



> There is no end in sight to these spiralling insulin prices.
> 
> This is great for the bottom line of insulin manufacturers, but
> diabetics who need insulin are paying way too much for something that,
> at best, offers nothing more than older and much cheaper brands.
> Canadians Banting and Best, who discovered insulin, gave the insulin
> patent to the Canadian people so this vital life-saving medicine would
> be available at cost. This fine legacy is being buried by me-too
> insulins and, I fear, do-nothing governments.
>
> Colleen Fuller


Comment:

Garbled history. Which is not surprising since it's a complex one. I
would recommend Michael Bliss' book THE DISCOVERY OF INSULIN (1982, U
Chicago Press) which I've read, and I suggest Colleen Fuller read also.

Without going into boring detail: Insulin was discovered by a lot of
people, including Collip, who got short shrift.  The first Canadian
patent was actually in Banting and Collip's names, since they were the
only non-physicians on the Canadian team (it being through more seemly
not to have physicians making patent money).  Dr. Best was added later
only because patents can be invalidated in not including all
discoverers.

THAT patent actually got rejected on the American side since the
American Zuelzer in 1912 had already patented a glucose-lowering
pancreatic extract. Which is all there were, even in 1922 when the
Canadians were trying to patent-- the structure not being known. The
Canadians and Lilly in America had to go to some lengths to convince
the patent office they had some new process for extraction.

As for giving the patent to the "Canadian people," that's nonsense,
unless the Canadian people all hang out at U Toronto. Collip and Best
and Banting worked at the U. of Toronto, and they turned over patent
control to the University board of regents, which continued to use
licensing proceeds for university projects and purposes. A similar
thing would happen today, albeit with a lot more paperwork.

SBH

Intern Med J. 2005 Sep;35(9):536-42.

Glargine is superior to neutral protamine Hagedorn for improving glycated
haemoglobin and fasting blood glucose levels during intensive insulin
therapy*.

Fulcher GR, Gilbert RE, Yue DK.

Department of Diabetes, Endocrinology and Metabolism, Royal North Shore
Hospital, New South Wales, Australia.

Aim: To compare glycaemic control and symptomatic hypoglycaemia rates
with glargine versus neutral protamine Hagedorn (NPH) in poorly
controlled type 1 diabetes patients. Methods: Patients (n = 125) received
preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63)
at bedtime for 30 weeks in a multicentre, randomized, single-blind (a
blinded investigator made titration decisions) study. Basal insulin
dosage was titrated to achieve fasting blood glucose (FBG) values <5.5
mmol/L. Results: Baseline characteristics were similar for the two groups
(mean diabetes duration 17.5 +/- 10.1 years) except mean glycated
haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group
(9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was
8.3 versus 9.1% for the glargine versus NPH groups.  Adjusted
least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a
significant treatment benefit of 0.53% for HbA(1c) in favour of glargine
(P < 0.01). Mean baseline FBG were similar for the glargine and NPH
groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus
9.0 mmol/L.  Adjusted LSM change from baseline was -3.46 versus -2.34
mmol/L, with a significant difference of 1.12 mmol/L in favour of
glargine (P < 0.05).  There were similar total numbers of daytime mild,
moderate or severe hypoglycaemia episodes in the two treatment arms.
However, significantly fewer moderate or severe nocturnal hypoglycaemic
episodes were observed in the glargine group (P = 0.04 and P = 0.02).
Conclusion: Glargine is superior to NPH for improving HbA(1c) and FBG
levels during intensive insulin therapy in patients with type 1 diabetes,
and is associated with less severe octurnal hypoglycaemia.  (Intern Med J
2005; 35: 536-542).

PMID: 16105155 [PubMed - in process]

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,talk.politics.medicine,
	misc.health.diabetes,alt.support.diabetes
Subject: Re: insulin and me-too drugs: Fuller responds to Harris
Date: 11 Sep 2005 16:14:52 -0700
Message-ID: <1126480492.562476.108030@g43g2000cwa.googlegroups.com>

> Colleen Fuller:
> There are higher insulin antibody levels in beef as compared to pork.
> There are not significant differences between pork insulin and
> recombinant DNA human insulin.
>
> A 2002 Cochrane review of the evidence on recombinant human insulin
> (Richter B, Neises G. 'Human' insulin versus animal insulin in people
> with diabetes mellitus (Cochrane Review). In: The Cochrane Library,
> Issue 3, 2002. Oxford: Update Software) found that "At the time of
> introduction of human insulin, marketing strategies suggested that the
> lower immunogenicity of human insulin and the anticipated decline in
> antibody titres would offer a clinical advantage for insulin-treated
> patients". This appears to have been a "theoretical" advantage,
> not a real one.


COMMENT:

The Cochrane Review's point of view is that the human insulins were
introduced into the market without adequate long term safety and
efficacy testing. That's surely a matter of taste. But the review's
suggestion that it was somehow mere "marketting strategies"[!] that
"suggested that the lower immunogenicity of human insulin and the
anticipated decline in
antibody titres would offer a clinical advantage for insulin-treated
patients," is nonsense!

At the time, no endocrinologist (involved in marketing or not) guessed
otherwise (if you want to argue that, find me the cite). Nor did the
Cochrane Review suggest (before the fact) that it might not be the
case. This result took EVERYBODY by surprise: industry, academia,
practising physicians and patients, alike.

It's simply the usual socialist boloney For Cochrane to blame this odd
outcome and failure to se the future, in retrospect, on some capitalist
mechanism.  Where were the non capitalists of the time, in opposition?

Recall the days of yore. I was there. The mid 1980's were a time when
at least 2 injectable protein products (Growth hormone and Hep B
vaccine) HAD to be switched to genetically engineered products without
a long and leisurely safety and efficacy comparison trials, because the
previous products had come from human sources that were no longer
possible to use, on very short notice (in once case due to CJD, and in
the other, due to HIV in donor pools). This was NOT a time when any
serious voices were suggesting that the project to replace animal
insulin be treated any differently, even though it (in theory and in
retrospect) could have been done.


> "Human" insulin is not less likely to produce antibodies than pork
> insulin. We know why those who use pork or beef insulin produce
> antibodies, but it's not clear to me why antibodies result from the
> use of an insulin whose molecular structure is identical to the human
> insulin molecule. Some (Lewontin, eg.) have suggested that the folding
> and unfolding action that is used to produce the human insulin molecule
> is responsible for some of allergies and other problems associated with
> the resulting insulin.

COMMENT:
Yup. In other words, it's still a big mystery, and weird one. The idea
that its future posiblity, 20 years ago, might have been rationally
used to uphold the development of a multi-billion dollar industry, is a
completely out-to-lunch idea. We'd still be waiting for human insulin.
And probably criticized by all the people who complain we still produce
flu vaccine in chicken eggs.

> Colleen Fuller:
> Novo Nordisk withdrew all of its animal insulins from the Canadian
> market, and most from the US market, in 1995. Novo distributed a broad
> range of beef, beef/pork and pork insulins (Toronto, NPH, Ultralente,
> Semilente and Lente, among others and in all three formulations)
> through Connaught. Eli Lilly withdrew all of its beef insulin from the
> North American market in 1998. On July 6, it announced it was pulling
> the remaining two types of Iletin II pork insulin.
>
>
> Steve Harris:
> Beef insulin is no longer available due to mad
> cow disease.
>
> Colleen Fuller:
> Without discounting concerns about BSE, most physicians incorrectly
> believe that beef insulin was withdrawn because of BSE (or antibodies).
> The fact is that beef insulin was withdrawn by manufacturers purely as
> a marketing strategy.

COMMENT:
"Marketing strategy" meaning anticipation of much stricter regulation
on injectables made from cow innards (the BSE prion is MUCH tougher
than the insulin molecule--- you tell ME how they're going to make sure
you get the insulin and not the prion.)

But you've got me. I didn't think anybody could still be that stupid as
to continue to produce beef insulin in this day and age, but
apparently, there are some people who still are. But let me put it on
record here and now, WHY and think it's stupid, and predict that more
trouble is to come from it. And that you disagreed with me.


> Regulators did not require its withdrawal, and it
> continues to be marketed in the United Kingdom (where 20% of diabetics
> use animal-sourced insulin), Australia, India and many, many other
> countries, along with pork insulin. It is safe, effective and
> affordable.

COMMENT:
Ahem. "Safe" you say?  On the basis of *what* BSE-centered studies of
beef insulin manufacture? How much looking at the issue has anybody
really done? Where is COCHRANE'S concern about safety issues when we
really need them?

By the way, regulators did not require withdrawal of beef insulin in
the US, because they didn't need to. Companies withdrew voluntarily.
But the FDA does indeed have concerns about BSE in beef insulin
imported from other countries, and is on record about it.

http://www.fda.gov/cder/drug/beefandporkinsulin/default.htm#Q-1


> Steve Harris:
> Pork insulin is available just about everywhere,
> including Canada (where about 200 Canadian still us it).
>
> Colleen Fuller:
> IMS data suggest there are roughly 700 people using Iletin II NPH and
> Regular insulin in Canada. Eli Lilly estimates about 400 people. On
> July 6, Eli Lilly announced it is pulling the remaining pork insulin
> from the North American market. Wockhardt, based in India, has applied
> for a license to market its own brand of pork insulin in Canada, but
> not in the United States. They have been assisted by Eli Lilly, whose
> own Canadian supplies will be exhausted by April '06.

COMMENT:
Well, good for them. If you can find a little niche market, like people
who think that vacuum radio tubes give better amplifier sound, have at
it. I'm sure that being Canadian, you'll want the government to pay for
it, though.

> Colleen Fuller:
> The biggest impediment to those who try to manage their blood sugars
> effectively is doctors who are ignorant of the issues and evidence
> regarding animal-sourced insulin. In 1995, Humulin was among the top 10
> drugs with reported serious adverse side effects in the United States.
> Humalog has racked up an astonishing number of reported serious ADRs in
> Canada. Although these are suspected links only, there has been no
> attempt in Canada to determine causality. (I recognize that this would
> be difficult; however it's impossible to say how difficult since the
> national regulator hasn't ventured to find out.). The point is that
> the experiences patients have had are very real, and the attitude of
> many physicians is appalling. These patients are accused of being
> nothing more than some kind of modern-day Luddites, when in fact
> what's happened to them is that they were using the wrong species of
> insulin. There are too many irresponsible doctors to whom these often
> desperate patients turn - and this hard-hearted and ignorant attitude
> is what they have to deal with. It's really unbelievable.
>
> It's also unbelievable that there are some doctors who compare a
> vital life-saving medicine like animal insulin to vinyl records and
> 8-track tapes. They shouldn't be treating patients in the real world
> of drug safety and effectiveness. Two national regulators - Canada
> and the United Kingdom - have concluded that there is a subset of
> diabetes patients who require animal insulin. After many years of
> persistent work by insulin-dependent diabetics, a Health Canada
> representative stated before the Parliamentary Standing Committee on
> Health, that "there very clearly are Canadians who need animal-sourced
> insulins to manage their diabetes. We have no doubt about that at
> all...The current science [sic] knowledge does not really enable us to
> understand why the synthetic insulin or the human insulins do not work
> as well for some people as do the animal insulins, but clearly that is
> the case..." (Evidence before the Parliamentary Standing Committee on
> Health, presented by Julia Hill, Director General of the Biologics and
> Genetic Therapies Directorate, Feb 2003) In July, the MHRA acknowledged
> that some people must have guaranteed access to natural (beef and pork)
> insulin. The Australian government has recognized this situation with
> its approval of Wockhardt's beef (but not pork) insulin, which is
> sold there by Aventis. In India a battle is raging to protect
> animal-sourced insulins and domestic control over the insulin market.
> In Europe many diabetics are fighting to maintain access to pork
> insulin.
>
> Of all the comments and ignorance exhibited by this physician, his
> dismissal of the actual and sometimes traumatic experiences diabetics
> have had is very disturbing. Patients who experience serious adverse
> side effects have to fight for recognition without the support and
> advocacy of doctors who claim to have the patient's best interest at
> heart. No wonder so many patients feel demoralised and humiliated.


COMMENT:

STOP! ENOUGH! Here's where we get to brass tacks.  The Cochrane review
you've already quoted is (despite its unfortunate politics) still the
best that exists on the subject, and it contradicts you. You cannot
have it both ways. Let me quote from COCHRANE, and please note my
emphasis *** asterisks:

Richter B, Neises G. 'Human' insulin versus animal insulin in people
with diabetes mellitus (Cochrane Review). In: The Cochrane Library,
Issue 3, 2002.

Main results
Altogether 2156 participants took part in the 45 randomised controlled
studies that were discovered through extensive search efforts. Though
many studies had a randomised, double-blind design, most studies were
of poor methodological quality. Purified porcine and semi-synthetic
insulin were most often investigated. ***No significant differences in
metabolic control or hypoglycaemic episodes between various insulin
species could be elucidated. Insulin dose and insulin antibodies did
not show relevant dissimilarities.***

Authors' conclusions
**A comparison of the effects of human and animal insulin as well as of
the adverse reaction profile did not show clinically relevant
differences.**

COMMENT:
There you are. The best evidence doesn't support you, although COCHRANE
does of course say that more study is needed since:

"Many patient-oriented outcomes like health-related quality of life or
diabetes complications and mortality were never investigated in
high-quality randomised clinical trials."  In other words, we need more
information on that point. But it's not available. Anecdotes and
politics and speeches to "Parliamentary Standing Committees" by special
interest groups, do not provide it. They are not science.

MY COMMENT:

So--- you and the Canadian government are quite welcome to fund and do
some studies of the type that COCHRANE calls for. In the manner of all
socialists, they want more medical information safety and want the
capitalists to provide this information, but refuse the capitalists
license to make any money to do so, until the information is in. Which
results in nothing happening.

Personally, I'm always happy to have more information about ANY drug.

Meanwhile, you want the entire system to change because of a couple of
hundred diabetics, who say they don't get the same results with the new
stuff as the old.   But there we have the difficulty.  I wish I had
nickel for every person I've heard say "Every person should be
guaranateed the same standard of health care by his or her society"!
And I wish I had a nickel for every patient who told me "But doc, I'm
not LIKE everybody else! Drugs react completely OPPOSITE on me!!"  And
I wish I could put the two groups together to argue out the
consequences of these two points of view, one political and one
personal---- because in reality they make a mighty poor mix.

But that's the problem with democracy: everybody has to take what only
the majority deserve. You democratized health care in Canada, and that
means you completely *screwed* any small groups of people who don't
tolerate any treatments well that the majority have no problem with.

Thus, it's your bed, so lie in it. Till (somebody-- who knows who) does
the needed research, for free, for you. And hopefully, in the meantime
you won't have a hypoglycemic episode in the night, due to the
unintended consequences of your collectivist politics, impacting on
your (obviously) highly individualized physiology.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,talk.politics.medicine,
	misc.health.diabetes,alt.support.diabetes
Subject: Re: insulin and me-too drugs: Fuller responds to Harris
Date: 14 Sep 2005 03:32:08 -0700
Message-ID: <1126693927.998574.215720@o13g2000cwo.googlegroups.com>

Alan Mackenzie wrote:
> Steve Harris <sbharris@ix.netcom.com> wrote on 11 Sep
> 2005 16:14:52 -0700:
> >> Colleen Fuller:
>
> >> A 2002 Cochrane review of the evidence on recombinant human insulin
> >> (Richter B, Neises G. 'Human' insulin versus animal insulin in people
> >> with diabetes mellitus (Cochrane Review). In: The Cochrane Library,
> >> Issue 3, 2002. Oxford: Update Software) found that "At the time of
> >> introduction of human insulin, marketing strategies suggested that the
> >> lower immunogenicity of human insulin and the anticipated decline in
> >> antibody titres would offer a clinical advantage for insulin-treated
> >> patients". This appears to have been a "theoretical" advantage, not a
> >> real one.
>
> > COMMENT:
>
> > The Cochrane Review's point of view is that the human insulins were
> > introduced into the market without adequate long term safety and
> > efficacy testing. That's surely a matter of taste.
>
> No.  It's a matter of clinical judgement.  The difference being that in
> matters of taste, yours and mine are just as valid as anybody's.


COMMENT:
Not really in this case, since I'm a doctor and you're not. I saw a lot
of patients changed from animal to human insulin in the 80's without
real problems. Some people did complain of shorter actions, but this
was usually fixable by adding more long-acting to the mix. And usually
wasn't as a bad as individual variations on different days, anyway.


> > But the review's suggestion that it was somehow mere "marketting
> > strategies"[!] that "suggested that the lower immunogenicity of human
> > insulin and the anticipated decline in antibody titres would offer a
> > clinical advantage for insulin-treated patients," is nonsense!
>
> I read that review once.  Nowhere do I remember them mentioning
> market[t]ing stragies.  As for "suggesting" them - Any such suggestion
> would have been in the minds of the readers.

COMMENT:
Well, I do remember it, and it's quoted by Colleen above. So unless you
can find a copy of the review on the web, we'll just have to leave it
at that.


> > At the time, no endocrinologist (involved in marketing or not) guessed
> > otherwise (if you want to argue that, find me the cite). Nor did the
> > Cochrane Review suggest (before the fact) that it might not be the
> > case. This result took EVERYBODY by surprise: industry, academia,
> > practising physicians and patients, alike.
>
> This is the sort of reason why most drugs have to undergo proper testing
> before being introduced.  Why genetically engineered insulin was allowed
> to be an exception is the real mystery.

COMMENT:
It was testing in all kinds of ways. You can look at medline at the
many studies of human insulin in the mid 80's.  You think it should
have been tested more. So? Diabetic complication and mortality studies
take a LOT of time and money. Those weren't done for most of the
various animal insulins until decades after introduction. Or quality of
life studies, either. You want a completely different standard here for
GE products. I don't think it's warrented.


> > It's simply the usual socialist boloney For Cochrane to blame this odd
> > outcome and failure to se the future, in retrospect, on some capitalist
> > mechanism.  Where were the non capitalists of the time, in opposition?
>
> Cochrane restricted its discussion to purely medical and scientific
> matters.  Nowhere did it mention political matters.

COMMENT:

We've been over that. If they said what they are quoted as saying, as I
believe they did, it's an overtly political statement.

> I was there too.  And my insulin was casually switched over to GE insulin
> by my doctor (A GP, not a diabetes specialist of any sort).  The new
> stuff wasn't as good as the old.  Unlike the drugs you are referring to,
> the were no pressing reasons to stop using natural insulin.


COMMENT:
Well, you could have gone back. At that time, where was no reason not
to.


> Quite likely, the "human" insulin molecule is not identical to the human
> insulin molicule at all; .


What makes you say that? Evidence, please?




> > COMMENT:
> > Yup. In other words, it's still a big mystery, and weird one. The idea
> > that its future posiblity, 20 years ago, might have been rationally
> > used to uphold the development of a multi-billion dollar industry, is a
> > completely out-to-lunch idea. We'd still be waiting for human insulin.
>
> No, we wouldn't.  There were people then who were allergic to pork and
> beef insulin, just as there are people now who are allergic to GE
> insulin.  Other than for those few people, there was no need for GE
> insulin.  It would have been developed (and nobody's suggesting it
> shouldn't have been) simply because it's much cheaper to get insulin out
> of a tampered-with tummy bug or yeast cell, than out of a slaughtered pig
> or cow.  The real mystery is why the regulatory authorities were asleep
> at the wheel, and allowed it to be introduced withoug being properly
> tested.

COMMENT:
It was as well tested as any of the things it was competing against,
and far better than insulins were tested during the first half century
they were used.

Let's see you find me a quality of life study for beef vs. pork insulin
done prior to 1985.


> No.  "Marketing strategy" here means forcing diabetics to convert to a
> drug more profitable for the manufacturers, regardless of how well it
> works.  Willbill has pointed out on this newsgroup (misc.health.diabetes)
> that bovine products are used in the manufacture of Lantus, for example.


I can't find that cite. Cite please?  I don't believe it.


> > On the basis of *what* BSE-centered studies of beef insulin
> > manufacture? How much looking at the issue has anybody really done?
> > Where is COCHRANE'S concern about safety issues when we really need
> > them?
>
> Do we really need them?  Beef insulin has been used continuously for
> decades, all through the BSE scares of the last ten years.  The
> manufacturers are careful in the extreme, where their bits of cow come
> from.  If BSE in insulin were a problem, wouldn't we know about it by
> now?  There'd already be a few hundred deaths from this cause, wouldn't
> there?


COMMENT:
Maybe. Maybe not. BSE in people (vCJD) took some time to show up in the
beef eating population, and they never did pin it all down. Where the
beef comes from to make insulin may not be the same places. How do you
know what the epidemic looked like in those years and how careful the
manufacturers were? Can you trace your bottle of beef insulin back to
the herd it came from, and when? And do they have tests on those cattle
on file? Are these German beef? It's all a bloody awful problem, and
far more difficult than the food problem.


> Anyhow, what about the same measures applied to Lantus, for example?  It
> too uses beef products in its manufacture, and is used by far more people
> than beef insulin.

Again, I want to see evidence of that. If they just get the arginine
from beef, that's a chemical. In THAT case, the prion, as protein, is
surely destroyed. So it hardly counts with injecting one protein with
another, the way they used to do with human growth hormone. Which DID
give people CJD.


> Which raises the much bigger philosophical question, should we diabetics
> be expected to have to chose from amongst whatever drugs Novo, Lilly and
> Aventis find profitable to make?  That is pretty much the way things are
> at the moment.  The other extreme would be for regulatory bodies to
> specify rigidly what products are to be made.  Doesn't seem much better.
> The real problem is, the supply of insulin is a monopoly, not a free
> market.  If I had my way, there _would_ be a free market, one in which
> the existing monopolistic powers would be severely curtailed.

COMMENT:
I'm a libertarian. I think it should be entirely a free market, though
perhaps with some UL-like safety inspection or
kosher-certification-like inspection, which you demand in your products
if you like.

I do realize there are some orphan drugs and orphan diseases. That's
what charities are for. There are some odd allergies. But there are
many different human insulins from many sources.

Finally, I doubt that semi-synthetic pork insulin will ever disappear.
So you'll always have that.


> When I needed an insulin change a few years back, my last doctor told me
> "convert to Lantus, go onto the pump, or stay with GE NPH[*].  I refuse
> to even consider animal insulin.".  I found a more suitable doctor.
>
> [*] For those not in the diabetic groups, NPH is a delayed action
> insulin, delayed by protamine extracted from fish testicles, and is
> notorious for causing symptom-less hypos (low blood sugar), and having an
> enormous action peak around 4-6 hours after injection.  YUCK!!


COMMENT:

Curious: Where are you getting your long acting beef insulin without
protamine in it? I suppose it would be beef lente or ultralente? Not
PZI or isophane.


> There was, and is, however, massive and incontrovertible anecdotal
> evidence that GE insulin produces problems for many people.  There is no
> convincing evidence and no reason whatsoever to believe that GE insulin
> is free of problems.

COMMENT:
"Massive and incontravertable anecdotal evidence." Sigh. Why can't we
get one of these people into a laboratory?  Does the effect go away?

I'm not saying it can't be true. I'm just wondering why it's not better
documented.


> > Authors' conclusions
> > **A comparison of the effects of human and animal insulin as well as of
> > the adverse reaction profile did not show clinically relevant
> > differences.**
>
> Yes.  As you mention, most of the testing was poor quality, and didn't
> take into account quality of life issues.  Tell me, in treating a chronic
> disease, is there anything apart from quality of life which is worth
> testing for?


Nothing, but quality of life is highly susceptable to placebo issues.
Which means you need to do it in the hospital, blinded.



> > Meanwhile, you want the entire system to change because of a couple of
> > hundred diabetics, who say they don't get the same results with the new
> > stuff as the old.
>
> It's not a "couple of hundred".  It's many, many thousands, probably
> millions, worldwide.  You're dismissing their problems as something
> frivolous.  Amongst them are a few who are allergic to GE insulin, who
> will die rapidly and nastily without natural insulin.  One of them is
> called Sabine Hancl and posts here (misc.health.diabetes) from time to
> time.  Her worst experience was being admitted to hospital in an
> emergency and being injected with GE insulin, despite her wearing a
> medical tag stating her allergy to it.  Within hours she was on the brink
> of death, with kidney failure amongs other things.  She spent a year in a
> psychiatric clinic as a result.


COMMENT:
A good story, but human insulins are made in at least three organisms.
Which one is she allergic to? Also, by the way, anybody who spends a
year in a psych clinic due to an allergy might have needed the psych
clinic to begin with--- did you ever consider that? It's not a usual
result. (Neither, by the way, is renal failure). Do you believe all
stories you hear on the web?

> In this particular case, natural insulin works better for many people,
> amongst them me.  There has never been any convincing evidence that GE
> insulin works consistently well.


There is convincing evidence all over medline. Look it up.


> For many people, the difference between
> natural insulin and artificial is the difference between being a fully
> functional healty person and an invalid, barely able to hold down a job.

Sez you. Let's see this effect double-blind.


> The production of natural insulin is fully economic and profitable.  I do
> not find it unreasonable to require it to be manufactured.


I do if it's not profitable. And if it is pofitable, you won't need to
require it.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,talk.politics.medicine,
	misc.health.diabetes,alt.support.diabetes
Subject: Re: insulin and me-too drugs: Fuller responds to Harris
Date: 14 Sep 2005 15:30:35 -0700
Message-ID: <1126737035.456513.21140@f14g2000cwb.googlegroups.com>

Alan Mackenzie wrote:
> How do you know I'm not a doctor?  OK, I'm not, but how did you know?


That you went to your doctor and got changed to some other kind of
insulin by him, was a clue. Doh.


> Or
> were you just guessing?  I didn't know before now that you were a doctor.
> I take it this means "healer of the sick", not PhD;  do you have as a
> speciality the treatment of diabetes?  In any case, it's _still_ not a
> matter of taste.


I'm an internist by training. Not as good as an endocrinologist as
regards this discussion, for sure.

Some clnical judgements are matters of taste, and others aren't.

Generally, when you see some big "concensus" report in the medical
literature, that's a clue that there's really no consensus. If there
was, there'd be no reason for the report. Nor do such reports really
help.

As for Cochrane, they can demand any standard of knowledge for new drug
introduction they like, after the fact. It's not their money.

As for the companies going to new preparations of new human insulins to
extend their patent protections, of course you're right. But without
the regulatory burdens in the drug industry, economic barriers to entry
by companies desiring to produce new off-patent generics, wouldn't be
so high. So there's enough blame here to go around.

I just wish Cochrane spread it more equitably. Their story is
"marketing" drove these new products into clinical use too fast, and
"marketing" has kept them there. But if the new products are truly
inferior, that can't happen without some kind of physical force being
brought into play. In a truely free market, cheaper better products
continue to be available, because there's demand for them (see
Walmart). If it doesn't happen that way, you can't blame business
directly. They don't have any police or jails of their own, to use upon
their would-be competitors. If monopoly happens, you have to put the
blame entirely where it belongs: with the government. And in a
democracy, that means with the voter. Which means, your next door
neighbor.

Likely as not, your next door neighbor is frightened to death of newly
indroduced drug products by new companies, and imported drugs, and
generic drugs. And wants the FDA to really scrutinize these carefully,
making them do all the expensive clinical trials you caomplain of the
lack of. But *that's* the econonomic barrier. That's the unintended
consequence.

As it happens, I also have some experience with drug development. I'm
writing up a QC sequence for the cGMP manufacture of a generic drug by
a US manufacter right now. But it won't be FDA approved at first, so it
will be sold overseas. Just to apply for an FDA NDA for a VETERINARY
market drug (this is NDA because a new formulation of a generic),
carries a $130,000 application fee.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: misc.health.diabetes,sci.med
Subject: Re: U.K. expands animal insulin production
Date: 22 Sep 2005 17:02:36 -0700
Message-ID: <1127433756.822672.292180@f14g2000cwb.googlegroups.com>

fresh~hor...@despammed.com wrote:
> http://www.iddtinternational.org/
>
> "The Dept of Health fully accepts that some people are better suited to
> animal insulin, and that animal insulin should continue to be
> available."
>
> "Wockhardt UK are expanding their production capacities over the next 6
> to 12 months to include animal insulins."


COMMENT:

Yes, but don't read anything into this per se. The Department of Health
also "acknowledges that "complementary therapies have been known to
help alleviate the symptoms of certain illnesses in cases where
orthodox medicine does not seem to have offered a complete solution."

Which means in practice that they're not in principle adverse to paying
for aromatherapy and homeopathy if that's what people want, and it's
cost effective.

http://www.nhscareers.nhs.uk/nhs-knowledge_base/data/7800.html

I can't help but wonder: if human insulin had been synthesized and
given first, and very recently some pharm company had come up with a
plan to extract insulin more cheaply from pig pancreas and cleave off
the terminal amino acid, claiming that this would make it chemically
essentially the same as human, and no more antigenic, and decided that
this would be what most diabetics would henceforth get, like it or not,
what would happen.

I suspect that various health watchdog groups would be going absolutely
ape%$#@. I don't think we'd ever hear the end of it from Muslims about
unknown pig viruses and from Hindus about possible cow prions. And
British antivivisectionists would be in insulin shock.

Instead, it's happened the other way around. Most diabetics get
genetically engineered insulin. Probably while campaigning against
genetically engineered cereal. Oh, well.

SBH