The annual cost of diabetes drugs in the USA have nearly doubled to $12.5 billion between 2001 and 2007, raising questions about whether this actually translates into improved care.

That is the concern expressed in a study by researchers at Stanford University and the University of Chicago and published in the Archives of Internal Medicine. Randall Stafford, senior author of the study, noted that “this near-doubling of diabetes costs may partly reflect better care, but we need to step back and examine the value of newer and more costly medications that may be overused”.

A major problem, according to Caleb Alexander, the study's first author, is that approval by the US Food and Drug Administration does not require that a treatment be compared against alternative medicines – it only has to be safe to use and better than a placebo. Nor, he noted, does a company have to demonstrate that a drug's effectiveness justifies its price.

New drugs such as Merck & Co’s dipeptidyl peptidase-4 inhibitor Januvia (sitagliptin) and Amylin/Eli Lilly’s glucagon-like peptide-1 analogue Byetta (exenatide), priced at $160 and $210 per prescription respectively, cost eight to 11 times more than older, generic drugs such as metformin or glipizide. They are marketed with claims of greater convenience and better control of blood sugar levels, and physicians have increasingly used them as alternatives to injected insulin, Dr Alexander said, noting that insulin use has dropped from 38% of treatment visits in 1994 to 28% in 2007.

However Dr Stanford claims that “just because a drug is new or exploits a new mechanism does not mean that it adds clinically to treating particular diseases," he said. "And even if a new drug does have a benefit, it's important to consider whether that benefit is in proportion to the increased cost of new therapies." The study also found that patients are increasingly being prescribed more than one medication. In 1994, 82% of patients were prescribed only one drug and last year only 47% were.

In a second AoIM article, a meta-analysis carried out by Elizabeth Selvin and colleagues at the Johns Hopkins Bloomberg School of Public Health, Baltimore, noted that metformin may be associated with a lower risk of death from cardiovascular disease. No associations were found between other diabetes drugs and beneficial or harmful cardiovascular effects, but that was in part because of insufficient data, the authors noted.

Most trials too short to spot adverse events
The meta-analysis, taken from 40 clinical trials published on or before January 2006, noted that “there have been few trials of oral diabetes therapies that have lasted longer than six months and that reporting of adverse events for cardiovascular disease is poor".

In an accompanying editorial, David Nathan, of Massachusetts General Hospital in Boston, wrote that “the current approach to assessing the relatively rare but clinically important adverse effects of diabetes management is unsatisfactory". He noted that the “vagaries of meta-analyses make them unreliable. On the other hand, increasing the size and duration of controlled clinical trials to provide adequate statistical power to detect relatively infrequent events would potentially bankrupt the pharmaceutical industry that supports most of the trials and delay the development of new drugs".

Therefore, new approaches are needed to ensure the safety of drugs without slowing development, Dr Nathan said. He suggests “the phased introduction of new medications with uniform, standardised collection of adverse outcome data [which] might identify relatively rare complications before the drugs are used by millions”.

The use of clinical databases may also provide an early alert regarding adverse outcomes, he concluded. In the meantime, “there are well-established and safe treatments that, if used aggressively, can improve the long-term health of patients with type 2 diabetes."