Launched with fanfare four years ago and available on the Pharmaceutical Benefits Scheme since last December, Actos and Avandia – the so-called glitazones – could dramatically improve blood-sugar control in people whose condition was otherwise intractable, said the study leader, Peter Colman, director of Royal Melbourne Hospital’s Department of Diabetes and Endocrinology. But the once-daily pills carried "significant risk of side-effects", said Associate Professor Colman, who analyzed the benefits and risks to more than 200 hospital patients treated with them.

Side-effects might have been underestimated in trials that treated those who were in better health, Associate Professor Colman said. It was "not an uncommon occurrence" for a drug’s downsides to go undiscovered until it was in widespread use.

A dangerous build-up of fluid in the lungs occurred in 2.5 per cent of the Melbourne patients – much higher than in previous studies, he said. The build-up occurred when the glitazones were given to patients with heart failure. While doctors were warned against prescribing them where heart failure was severe, "we found people with less severe cardiac problems did develop fluid overload".

Hypoglycemia, where patients can become irrational or lose consciousness, occurred in 15 per cent of cases – again much higher than standard warnings suggest – though all the cases were associated with taking other medications as well as Avandia or Actos. Other side effects included weight gain and water retention. So far there have been 162 formal reports Australia-wide of people who have experienced possible side-effects from Actos or Avandia, according to the Therapeutic Goods Association. It was also reported that six patients died, however five were already very ill and it was unclear whether the drugs contributed to their deaths.

Associate Professor Colman said he wanted to emphasize to doctors that diabetes drugs needed to be used with caution. "Careful patient selection and follow-up and realistic treatment goals are necessary," he writes in the Medical Journal of Australia.

Australia’s Health Insurance Commission shows subsidized prescriptions of glitazones have been rising steadily over the past year, reaching 20,000 in September. In order to qualify for subsidized status patients must be unable to take more established therapies.

Jeff Flack, the director of the Diabetes Centre at Bankstown-Lidcombe Hospital, praised the study, saying it was "important to have real-life experience". However, some of the patients’ treatment was not in accordance with current guidelines, which might have skewed the results, said Dr Flack, who is also president of the Australian Diabetes Society.

Paul Zimmet, the director of the International Diabetes Institute in Melbourne, said the patients attending the public hospital clinic in the study were likely to be poorer and have more medical complications than normal.