Doubts have also been raised following a review of a new class of drugs called thiazolidinediones. Rezulin (troglitazone) was one of the first to be licensed both in the UK and US. One recent study, carried out in France, found that 2 per cent of patients developed liver dysfunction, which can lead to liver failure, a potentially lethal side effect not noted by the drug company (Lancet, 2000; 355: 1008-10).
Released in the US in March 1997, troglitazone reached Europe later that year, but was withdrawn within weeks. Meanwhile, it went on to generate sales of over $2 billion in the US, and caused at least 90 cases of liver failure (70 resulting in death or transplantation) before it was finally withdrawn in March 2000.
Rosiglitazone and pioglitazone reached the US market in 1999 as first line agents to be used alone or in combination with other drugs. But in Europe, the same dossiers were used a year later to apply for a limited license as second line agents restricted to oral combination therapy. It seems extraordinary that these 'glitazones' could achieve blockbuster status without any clear evidence of advantage over existing therapy (Lancet, 2001; 357: 1870-5).
The side effects of one of the latest pioglitazones (Actos) which has been on sale in the UK since November also include upper respiratory tract infection, sore throat, headache, sinusitis, muscle pain and oedema.
Research carried out by the US Public Citizen's Health Research Group's Dr Wolfe into Food and Drug Administration (FDA) databanks also discovered that thiazolidinediones can lead to cardiac failure, "a serious finding not previously adequately acknowledged in the product labelling or on the company Web sites," he states.
Health threats are also present from other kinds of drugs.
Overweight diabetics often turn to weight loss drugs, but these come with their own problems. Fenfluramine can cause nausea, vomiting, headache, nervousness, irritability, bad dreams, insomnia, visual disorders, hypotension, impotence and loss of libido. Prolonged use may cause damage to the blood vessels of the lungs. Another drug for losing weight phentermine is also known to cause blurred vision, constipation, diarrhoea, dizziness, dry mouth, a false sense of well being, insomnia and nausea.
A recent report suggests that AIDS patients taking the antiviral drug abacavir might develop diabetes, although this reaction may be brought on by interactions with other drugs, such as hydro chlorothiazide and didanosine (N Engl J Med, 2001; 344: 142-4). In this case, the blood glucose levels in a 47 year old man with no family history of diabetes dropped dramatically while taking abacavir. However, within two weeks of coming off the drug, his blood glucose levels were back to normal.
Long term survivors of bone marrow transplants have a substantial risk of developing insulin resistance, impaired glucose tolerance and type 2 diabetes. These disorders increased in frequency in relation to time since the bone marrow transplant, and it looks as though glucose and insulin levels must now be added to the list of regular health checks in this vulnerable group of patients (Lancet, 2000; 356: 993-7).
And as if this wasn't enough, there's also the dangers with the use of insulin or oral hypoglycaemics with other drugs you may already be taking.
The AMA [American Medical Association] Drug Evaluations (Chicago: AMA, 1991) says that insulin taken with alcohol, clofibrate, fenfluramine, guanethidine, l-thyroxine, oxytetracycline, phenelzine, propranolol or timolol could cause "highly clinically significant" or "clinically significant" interactions, especially with prednisone. In the United States Pharmacopeia Drug Information (1992), this lattermost drug is described as having an interaction of "major significance".