The Concerns of Patients are Justified

GM Vs animal insulin

Choices – The Evidence
Evidence from people with diabetes
A little bit of history
Facts
Action and duration times of animal and GM ‘human’ insulins
Hypoglycaemia and loss of warnings
‘Dead in Bed Syndrome’
The concerns of patients are justified
Availability of animal insulins in the UK
Changing your insulin
What to do if your consultant refuses to change your insulin
Availability of animal insulin if admitted to hospital
Frequently asked questions
Allergic reactions to insulin

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The concerns of patients are justified

While many medical and health professionals chose to dismiss the evidence from patients of side effects when using ‘human’ insulin, the following statements support the concerns of patients:

British National Formulary [BNF] No 30, September 1995 page 280 (and also in the current edition) states:

Preparations of human sequence of insulin should theoretically be less immunogenic, but in trials no real advantage has been shown… Some patients have reported loss of warnings of hypoglycaemia after transfer to human insulin. Patients should be warned of this possibility and if they believe that human insulin is responsible for their loss of warnings it is reasonable to transfer them back to porcine insulins. When prescribing insulin great care should be taken to specify whether a human or an animal insulin is required. Indications for changing from animal to human preparations must be carefully considered in the light of these reported problems. Beef insulins are still available for patients who specifically request them.

Mims – the monthly index of medical specialities (current)
Patients transferred to human insulin should be advised that the early warning symptoms of hypoglycaemia may be less pronounced than with insulins from an animal source.

Novo Nordisk prescribing information for GM insulins 2003
Contraindications – Hypoglycaemia; hypersensitivity to human insulin or any of the excipients

Food and Drug Administration [FDA] Patient Information Leaflet
The warning in these leaflets in bold type in the insulin packs says:

"A few patients who have transferred from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycaemia were less pronounced or different."

NICE Clinical Guidelines on Glycaemia Control in Type 2 diabetes April 2002
The 2002 final guideline on Type 2 diabetes – glycaemic control and the use of insulin in the treatment of Type 2 as an adjunctive treatment, states the following:

"Despite the lack of an evidence-base to support current practice, the group recognised that usual insulin therapy both for people with diabetes starting and continuing insulin now utilised human species insulin rather than beef or pork. However the purified forms of these latter species of insulin are appropriate options for clinical and patient choice."

Aventis Pharmaceuticals, April 24th 2000 Press Release
"Human insulin therapy may be associated with hypoglycaemia, worsening of diabetic retinopathy, lipodystrophy, skin reactions (such as injection-site reaction, pruritus, and rash), allergic reactions, sodium retention and oedema."

Pulse, May 20th 2000
A spokeswoman for the Medical Defence Union is quoted as saying: "The data sheets for human insulin specify the potential for lowered hypoglycaemic awareness but GPs should take care to mention this to patients. Provided they did this, any legal claims in connection with human insulin would be directed against the manufacturers under product liability."

Department of Health September 2000
As a result of the adverse reactions to ‘human’ insulin and all the above statements, IDDT again entered into correspondence with the Medicines Control Agency and Lord Hunt, then Minister of State for Health. This resulted in the following statement from the Medicines Control Agency in Current Problems in Pharmacoviglance, Volume 25 Sept 2000:

Human Insulin
The Insulin Dependent Diabetes Trust, a patient representative group, has recently circulated a letter to some health professionals entitled ‘Important Safety Information on Human Insulin’ which suggests that there are concerns about the safety of human insulin.

A considerable number of scientific studies have been performed comparing animal and human insulin and the CSM has considered the available evidence on a number of occasions.

Although some patients have experienced problems on transferring from animal to human insulin, there is no evidence of a specific safety problem with human insulin, which is well tolerated by most patients.

We would like to reassure health professionals that there are no concerns regarding the safety of human insulin.

NB. It is notable that this statement from the Committee on Safety of Medicines differs from the 1998 CSM conclusion that "some patients …were better suited to continuing their treatment with animal insulins."

Press Release, Sept 9th 1999, Novo Nordisk, ‘human’ insulin manufacturers

…Historically improving glycaemic control with soluble human insulin has been associated with an increased risk of hypoglycaemia.

Committee on Safety of Medicines (CSM), August 19th 1998
A letter from Baroness Hayman, Parliamentary Under Secretary of State at the Dept of Health said:

"The CSM concluded that some patients did experience problems with human insulins, particularly when initially transferred from animal insulins and were better suited to continuing their treatment with animal insulins. However, the CSM found no evidence of a safety problem specific to human insulin. Indeed most patients respond well on it… To ensure that patients continue to have a choice of treatment both animal and human insulin will remain available."

Symposium on Childhood and Adolescent Diabetes, Scandinavia 1998
Individualised Insulin Therapy in Children and Adolescents
with Type 1 Diabetes – Acta Paediatr Suppl 425: 20-41, 1998

This paper was presented at a symposium in Scandinavia and the author’s group based in the US usually prefers to use pork insulin in the treatment of children with Type 1 diabetes. It cites a study in children under 5 years where HbA1cs were considerably lower with conventional therapy on pork compared to ‘human’ insulin. Also that in older children HbA1cs were no different but blood glucose levels were less erratic and easier to control on pork insulin. Insulin antibody production was no different for pork and ‘human’ insulin over a 5 year period.

The Lancet, 1998; Vol 352: 502-3
Professor Stephanie Amiel "Severe confusional hypoglycaemia in its extreme forms can destroy confidence, relationships and livelihoods, if not lives…The newer more purified insulins* probably compound the problem [of night hypos] by being just that little bit shorter acting than their predecessors."

*The reference to this statement is dated 1983 when the newer insulins referred to could only ‘human’.

The Lancet, 1998; Vol 352: 1549
Response to Professor Amiel – F Wolff, Hypoglycaemia Avoidance
This response in The Lancet pointed out that when insulin is extracted from the beta cells of the pancreas of pigs or cattle, small amounts of glucagon are also extracted from the alpha cells by the process itself and are therefore present in animal insulins. The author points out that the newer insulins [‘human’] do not contain glucagon. The significance of this is that glucagon is a counter-regulatory hormone and these hormones provide protection from hypoglycaemia by triggering the warning signs of an impending hypo.

Medical Monitor, September 9th 1996
Professor Harry Keen
Discussing Humalog at the European Association for the Study of Diabetes [EASD] 1996 Professor Keen is quoted as saying "No one wants a repeat of the problems that occurred when human insulin was introduced. We want to be absolutely sure that there is no repetition of that feeling among patients that they are being submitted to a new insulin which has not been carefully tried in all situations."

US Report of Post Market Adverse Drug Effects,1995, FDA
The 1995 table for reported post-market adverse drug effects in the US shows the top 10 suspect drugs. Humulin, ‘human’ insulin produced by Eli Lilly, is ranked number eight and is one of only three non-prescription drugs to be on this list. In 1995, the Medicines Control Agency in the UK did not make public their reported adverse drug reactions.

Drug and Therapeutics Bulletin, March 1989,
The then government sponsored safety bulletin, reported that ‘human’ insulin is no better than conventional insulin treatment and may hold dangers for people with diabetes. The Bulletin also said that ‘human’ insulin may cause loss of early warning symptoms of hypoglycaemia. (The Bulletin continued to maintain this stance.)