The best example for the drug industry fooling everyone is probably the development and marketing of the so called Human Insulin. The saga of Human Insulin is full of inadequate research, lots of cover up and twisted logic.
The facts are revealing:
Human Insulins are NOT Human Insulins. These are SYNTHETIC proteins that have a molecular structure akin to Human Insulin. These molecules are produced within the cells of microbes by recombinant DNA techniques.
These molecules were introduced into the market in the early 1980s with a claim that ‘Human Insulins’ are more efficacious and less (or not) allergenic than animal insulins. It was also claimed that Human Insulins would offer dose benefits (being more efficacious) and would therefore offset the higher costs. It was also claimed that with increased market share, the price of Human Insulins would ultimately come down. More than 25 years after the use of Human Insulins, none of these claims have been proven; in fact, all the evidence point to the contrary.
The initial study that was presented for obtaining the approval from US FDA involved only 17 non-diabetic men.(1) When reports of more frequent hypoglycemia (and unawareness to it resulting even in even deaths) started surfacing, a study from Liverpool University, involving just 7 patients, gave a clean chit to Human Insulin!(2) It is interesting to note that both these papers (1,2) were published in a journal as prestigious as The Lancet. Many such papers on the ‘virtues’ of Human Insulin have been published, obviously ‘supported’ by the Big Pharma. The Cochrane Review of 45 randomised controlled studies involving a total of 2156 participants reported thus: A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. (3) So much for the reliability of Human Insulins! And a scary precedent indeed!
Are ‘Human Insulins’ Better?
Human insulins have been reported to be as allergenic as animal insulins with antibodies reported in in as high as 55% of users. In addition, certain adverse effects unreported with animal insulins have been reported with human insulin. In the US, 2% of all ADRs have been from Human insulin users! Hypoglycemia is more common and its unawareness has resulted in many cases of ‘Dead in bed syndrome’. Problems like altered behaviour, unstable diabetes control, joint pains and many others have been reported among human insulin users. (More info at 4,5,6,7,8)
And now, certain genetically modified proteins, called as Insulin Analogues’, have been unleashed on the Human Market. These molecules have one or two amino acids in the insulin chain modified for the ostensible reason of altering the duration of action of insulin. The irony cannot be missed at all. When ‘Human Insulins’ were introduced, a big hue and cry were raised about the one and two amino acids that are different in porcine and bovine insulin respectively compared to human insulin. It was claimed that these differences are responsible for the allergenicity of animal insulins. Now, so called insulin analogues with experimental changes to insulin structure are being marketed! These molecules CANNOT be called as insulins at all for the simple reason that they do not have the structure of insulin. Nature does not work by splicing one or two amino acids here and there, it is more perfect. Take, for example, the case of hemoglobin. If glutamic acid is replaced with valine at the sixth position of the β chain of hemoglobin, it becomes Hemoglobin S that sickles under reduced oxygen levels and causes severe complications for the patient. What to say of proteins genetically modified from the insulin chain?
|Insulin lispro (Humalog)®||Reversal of the proline at B-28 and the lysine at B-29|
|Insulin aspart (Novolog)®||Substitution of proline by aspartic acid at B28|
|Insulin glulisine (Apidra)™||Asparagine at B3 is replaced by lysine and lysine at B29 is replaced by glutamic acid|
|(Lantus)®||Asparagine at A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain|
|Insulin detemir (Levemir)®||Acylation of a 14 carbon chain fatty acid (myristic acid) to the lysine residue at B29|
The story of introduction of these insulin analogues is the same, or even worse, than that of ‘human insulin’. Lantus was approved by the U.S. Food and Drug Administration in 2000. Before the European Medicines Evaluation Agency (EMEA) was asked to approve Lantus in Europe, “it was found to be highly mitogenic [causing cell proliferation] on in vitro testing with human osteosarcoma cells [cancerous cells from tissue surrounding bone].” It is said that Aventis, makers of Lantus, presented this information to the EMEA orally, and the EMEA decided it was “irrelevant.” Lantus was then approved.(9) Studies have reported that insulin analogues have been found to stimulate plasminogen activator inhibitor in vivo, increase the incidence of cardiovascular events and that certain analogs have IGF-1 effects in vitro and carcinogenic concerns in mice studies.(9,10) And for all these, these ‘analogues’ have not ben found to be any better than the already available insulins in the market.(11,12)
So, the writing on the wall is very clear:
- There is NO dose benefit with ‘human insulin’, and the cost is double that of animal insulin
- The claims of lesser side effects (particularly allergic reactions and antibodies) with ‘human insulin’ are unsubstantiated
- Natural animal insulin should be FIRST choice – cheaper, safer, effective
- Switch to ‘Human’ NOT recommended
- Switch back to animal insulin in case of problems with human insulin
- ‘Insulin analogues’ are NOT insulins and long term safety not proven.
- Keen H et al. Human insulin produced by recombinant DNA technology: safety and hypoglycaemic potency in healthy men. Lancet. 1980;2(8191):398-401
- Patrick AW et al. Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes. Dept. of Medicine, University of Liverpool, UK. Lancet. 1991 Oct 12;338(8772):950-1.
- Richter B, Neises G. ‘Human’ insulin versus animal insulin in people with diabetes mellitus. The Cochrane Database of Systematic Reviews 2005, Issue 1. Available at http://www.cochrane.org/cochrane/revabstr/AB003816.htm
- The GM ‘Human’ versus natural animal insulin debate. Available At http://www.iddtinternational.org/gmvsanimalinsulin/index.htm
- Paul Brown. Diabetics not told of Insulin Risk. Guardian UK 9 Mar 99 Available At http://www.mindfully.org/GE/Diabetics-Not-Told.htm
- Frank Lesser. ‘Human’ insulin loses its clean appeal. New Scientist. 15 April 1989. Available at
- Prasanna Kumar KM, Bhat GK. Animal Insulins – Current Status. Int J Diab Dev Ctries [serial online] 2003 [cited 2008 Apr 22];23:6-9. Available from: http://www.ijddc.com/text.asp?2003/23/1/6/26806
- Daniel Trecroci. Can Insulin Cause Cancer? Available at http://www.diabeteshealth.com/read/2006/02/01/4508.html
- Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, Kaiser T, Pieber TR, Siebenhofer A. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2007, Issue 2. Available at http://www.cochrane.org/reviews/en/ab005613.html
- Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, Gfrerer R, Pieber TR. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database of Systematic Reviews 2004, Issue 2. Available at http://www.cochrane.org/reviews/en/ab003287.html